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Cardiac Sarcoidosis Consortium
This is a registry study. The Cardiac Sarcoidosis Consortium (CSC) is an international, multicenter partnership among physicians and allied professionals at major medical centers with the unifying purpose to learn more about cardiac sarcoidosis through collaborative research.
Henri Roukoz
18 years and over
1209M20465
Inclusion Criteria:
• People who have been diagnosed with Cardiac sarcoidosis (CS)
• History of ventricular tachycardia or fibrillation
• Ventricular arrhythmias treated medically or with an implanted device
Heart & Vascular
Ventricular Tachycardia, Cardiac sarcoidosis, ablation, cardiac ablation, Clinics and Surgery Center (CSC)
DegenPRO: A multicenter prospective registry for the management of degenerative spine disorders
This is an observational registry database for adult patients diagnosed with degenerative spine disorders, which aims to add information to the understanding of the disease management of this spine diseases. By creating this registry, a more complete picture of degenerative spine disorders - including treatment practices - will be established, by collecting information about the health status of patients across several hospitals in several countries. Research of this kind will help future patients by providing doctors with information about degenerative spine disorders, and about patients' treatment outcomes. Data from this registry may be used to generate descriptive statistics on demographics, and clinical characteristics, including co-morbidities, treatment patterns and adverse outcomes (resulting from treatment or disease), as well as patients' quality of life measurements. Condition: Patients with a degenerative spine disorder Intervention/procedure investigated: No specific treatment required. Study design: Prospective case series
Christopher Martin
18 years and over
STUDY00000102
Inclusion Criteria:
Patient aged 18 years or older
Patient diagnosed with a degenerative spine disorder who receives treatment for the degenerative spine disorder
Patient capable of understanding the content of the patient information / Informed Consent Form
Patient willing and able to participate in the registry
Patient who has agreed to participate in the registry by providing consent according to the applicable local law and the declaration of Helsinki
Exclusion Criteria:
None Clinics and Surgery Center (CSC)
Measurement of Upper Aerodigestive Tract Pressures During Phonation
The purpose of this pilot research study is to test whether a tool called “High-Resolution Manometry” can diagnose laryngeal dystonia (also known as spasmodic dysphonia) and measure how well treatment works. High-Resolution Manometry measures pressures from a small catheter that is passed from your nose into your throat. We believe that pressures in the throat might be different for people with laryngeal dystonia than for people without laryngeal dystonia, or with other types of voice disorders. If we can diagnose laryngeal dystonia shortly after symptoms start, we can get patients the treatment they need sooner.
Jesse Hoffmeister
18 years and over
STUDY00015206
Inclusion Criteria:
Patients with adductor laryngeal dystonia and:
• experienced improvement in voice quality following injection of botulinum toxin into the thyroarytenoid complex
• received their most-recent injection within 6 months
• age 18-80 years old
• able to read and write in English
• For Healthy Controls:
• age 18-80
• have no known voice problem
• able to read and write in English Patients with Muscle Tension Dysphonia:
• Age 18-80 (age-and sex matched to adductor laryngeal dystonia)
• Diagnosis of primary muscle tension dysphonia by a laryngologist and speech pathologist in the ?...absence of current organic vocal fold pathology, [and] without obvious?neurologic etiology.?18
• Able to read and write in English
• Muscle tension dysphonia patients who either haven?t started voice therapy, or for whom symptoms persisted despite voice therapy
Exclusion Criteria:
For people with adductor laryngeal dystonia, Muscle Tension Dysphonia and healthy controls:
• diagnosis of vocal tremor, abductor laryngeal dystonia, any type of vocal fold lesion, or vocal fold paralysis
• known swallowing disorder (oropharyngeal or esophageal), with the exception of transient post-botulinum toxin injection-induced dysphagia
• pregnant
• prisoners
• allergy to topical anesthetic
• cannot fast for 6 hours (4 hour fast prior to study, up to 2 hours to complete the study)
• recent facial trauma
• recent nasal, pharyngeal, laryngeal, or esophageal surgery or obstruction
Ear, Nose & Throat
Clinics and Surgery Center (CSC)
ELEVATE, a global observational longitudinal prospective registry of patients with acute hepatic porphyria (AHP) (ELEVATE)
This is a global, multicenter, prospective, observational, longitudinal registry conducted to characterize the natural history and real-world clinical management of patients diagnosed with AHP. This protocol will not recommend the use of any specific treatments, visits, or procedures. No medication is provided as part of registry participation.
Gregory Vercellotti
12 years and over
STUDY00012826
Inclusion Criteria:
Documented diagnosis of AHP, per physician's determination
Exclusion Criteria:
Currently enrolled in a clinical trial for any investigational agent Digestive & Liver Health, Rare Diseases
Clinics and Surgery Center (CSC)
MT2021-33: Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial, with Cross-Over, of Posoleucel (ALVR105) for the Treatment of Adenovirus Infection in Pediatric and Adult Participants Receiving Standard of Care Following Allogeneic Hematopoietic Cell Transplantation
To compare the percent of participants who have clearance of AdV viremia at Day 29 in participants receiving posoleucel and standard of care to that in participants receiving placebo and standard of care.
Paul Orchard
SITE00001398
Inclusion Criteria:
Undergone allogeneic cell transplantation ≥21 days prior to dosing
Meet one of the below criteria:
AdV viremia DNA ≥10,000 copies/mL, OR
AdV viremia DNA results of ≥1,000 copies/mL, AND
has absolute lymphocyte count <180/mm3, OR
has received T cell depletion OR
had a cord blood transplant.
Exclusion Criteria:
Grade 3 or higher acute GVHD
Ongoing therapy with high-dose systemic corticosteroids
Uncontrolled viral (other than AdV), bacterial, or fungal infection(s)
Pregnant or lactating female unwilling to discontinue nursing prior to randomization
History of severe prior reactions to blood product transfusions
NOTE: Other protocol-defined inclusion/exclusion criterion may apply. Clinics and Surgery Center (CSC)
MT2020-27: Phase I/II Trial Using E7777 to Enhance Regulatory T-Cell Depletion Prior to Tisagenlecleucel (Kymriah) Therapy for Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
This purpose of this study is to identify a safe dose level for the study drug, E7777, when given with standard tisagenlecleucel therapy (also known by its brand name, Kymriah, is an immunotherapy that is made from the participants own blood cells) in participants with Diffuse Large B-Cell Lymphoma (DLBCL). Up to three dose levels of E7777 will be tested.
Veronika Bachanova, MD
18 years and over
STUDY00011895
Inclusion Criteria:
Diagnosis of a relapse or refractory (r/r) large B cell lymphoma, for which treatment with Kymriah is planned, including:
diffuse large B-cell lymphoma (DLBCL) not otherwise specified,
high grade B-cell lymphoma
DLBCL arising from follicular lymphoma
Considered at high risk for progression after CAR-T therapy by meeting one or more of the following factors:
refractory to last line of therapy
myc over expression >40% in any prior biopsy
≥2 sites of extranodal disease
Received two or more lines of systemic therapy
Has secured insurance coverage for Kymriah administration either in the outpatient or inpatient setting.
Age 18 years or older at the time of signing consent.
ECOG performance status of 0, 1, or 2
Adequate bone marrow reserve defined as:
Absolute neutrophil count (ANC) > 1,000/mm^3
Platelets ≥ 50,000/mm^3 (transfusion support can be provided)
Hemoglobin >8.0 mg/dl (transfusion support can be provided) Bone marrow involvement at disease assessment is an exclusion as these patients are at an increased risk of severe CRS and/or neurotoxicity
Adequate organ function at enrollment and within 14 days of planned E7777 treatment including:
renal function: eGFR ≥ 50 mL/min/1.73 m^2
liver function: ALT ≤ 3 times the upper limit of normal (ULN) for age, AST ≤ 3 times the ULN, total bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN (if liver is involved by lymphoma, the exception are allowed upon approval of PI)
albumin ≥ 3.0 g/dl
Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea (CTCAE v5) and pulse oxygenation SpO2 > 91% on room air. Pulmonary function tests within 28 days of enrollment: >50% corrected DLCO and FEV1
Hemodynamically stable and LVEF ≥ 50% confirmed by echocardiogram or MUGA
Life expectancy ≥12 weeks in the opinion of the enrolling investigator as documented in the medical record
Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use birth control for at least 30 days after study treatment or at least at least 4 months after the final dose of CY, whichever is longer Female participants: Two forms of birth control, one of which must be a barrier method, for example: use of intrauterine device (IUD) or oral contraceptives, plus a barrier method such as a condom, diaphragm or cervical cap Male participants: If possible to father a child (unless a successful vasectomy with confirmed azoospermia) participant and female partner, must use adequate contraception
Written voluntary consent prior to the performance of any research related tests or procedures
Exclusion Criteria:
Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to study enrollment to rule out pregnancy. All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing)
Known bone marrow involvement, if history of bone marrow involvement must have a BM biopsy to rule-out current involvement
Prior allogeneic transplant
Ocular disease or complaints visual acuity impairment, color or shape distortion, or blurred vision - potential participants are required to have an ophthalmological examine as part of screening
Known CNS involvement by malignancy - if clinically suspicious, must be ruled-out by examination of cerebrospinal fluid (CSF) by flow cytometry
Uncontrolled active hepatitis B or hepatitis C
Active or inactive HIV infection
Untreated active bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to enrollment)
History of heart failure or pulmonary edema, evidence of pleural effusion or active lower extremity edema
Uncontrolled unstable angina and/or myocardial infarction within 3 months of enrollment
Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion Clinics and Surgery Center (CSC)
MT2022-52: Allogeneic Hematopoietic Stem Cell Transplantation Using Reduced Intensity Conditioning (RIC) with Post-Transplant Cytoxan (PTCy) for the Treatment of Hematological Diseases
Stem cell transplants (sometimes referred to as a bone marrow transplants) have been done for over 40 years but research continues to further refine the method to reduce side effects without affecting transplant success. The purpose of this study is to improve on transplant outcomes while reducing the potential side effects based on what has been learned from previous transplant studies using a reduced intensity preparative regimen. Information collected during this study (transplant outcomes and side effects) will be compared with the outcomes of the previous reduced intensity conditioning transplant study that enrolled more than 300 patients since 2002.
Mark Juckett
Up to 75 years old
STUDY00017906
Inclusion Criteria:
Age 0 to 75 years of age with Karnofsky score ≥ 70% (≥ 16 years) or Lansky score ≥ 50 (< 16 years).
5/6 or 6/6 related donor, OR a 7-8/8 HLA-A, B, C, DRB1 allele match, OR a haplotype (at least 5/10) matched related donor. Donors will be requested to provide PBSCs although bone marrow is acceptable according to donor preference.
Eligible Diseases Acute Leukemias: Must be in remission by morphology (≤5% blasts) AND without evidence of MRD by flow cytometry, FISH, or conventional cytogenetics. PCR based MRD detection is not an exclusion to proceed.
Acute Myeloid Leukemia (AML) and related precursor neoplasms:
2nd or greater complete remission (CR); first complete remission (CR1) in patients > 60 years old; CR1 in ≤ 60 years old that is NOT considered as favorable-risk.
Favorable risk AML is defined as having one of the following:
t(8,21) without cKIT mutation
inv(16) or t(16;16) without cKIT mutation
Normal karyotype with mutated NPM1 and wild type FLT-ITD (unless persistently NPM1 positive by PCR following two cycles of chemotherapy)
Normal karyotype with double mutated CEBPA
Acute prolymphocytic leukemia (APL) in first molecular remission at the end of consolidation
Acute lymphoblastic Leukemia (ALL) /lymphoma:
CR2 or greater, CR1 unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities; CR1 high-risk ALL.
High risk ALL is defined as having one of the following:
Evidence of high risk cytogenetics, e.g. t(9;22), t(1;19), t(4;11), other MLL rearrangements, IKZF1
30 years of age or older at diagnosis
White blood cell counts of greater than 30,000/mcL (B-ALL) or greater than 100,000/mcL (T-ALL) at diagnosis
CNS leukemia involvement during the course of disease
Slow cytologic response (>10% lymphoblasts in bone marrow on Day 14 of induction therapy)
Evidence of persistent immonophenotypic or molecular minimal residual disease (MRD) at the end of induction and consolidation therapy.
Very high risk pediatric patients with ALL:
patients <21 years are also considered high risk CR1 if they had M2 or M3 marrow at day 42 from the initiation of induction or M3 marrow at the end of induction. They are eligible once they achieved a complete remission.
Biphenotypic/Undifferentiated/Prolymphocytic Leukemias in first or subsequent CR.
Chronic Myelogenous Leukemia in chronic or accelerated phase, or CML blast crisis in morphological remission (<5% blasts) and with negative MRD by flow cytometry (a positive PCR for BCRABL is acceptable for BMT): Chronic phase patients must have failed at least two different TKIs, been intolerant to all available TKIs or have T315I mutation. Patients with CML blast crisis in CR are only eligible if there is an feasible TKI maintenance plan following BMT.
Plasma Cell Leukemia after initial therapy, who achieved at least a partial remission; or relapsed and achieved subsequent remission (CR/PR) Myelodysplastic Syndrome: IPSS INT-2 or High Risk; R-IPSS High or Very High; WHO classification: RAEB-1, RAEB-2; Severe Cytopenias: ANC < 0.8, Anemia or thrombocytopenia requiring transfusion; Poor or very poor risk cytogenetics based on IPSS or R-IPSS definitions; therapy-related MDS. Blasts must be < 5% by bone marrow aspirate morphology. If ≥5% blasts, patient requires chemotherapy for cytoreduction to <5% blasts prior to transplantation Leukemia or MDS in aplasia. These patients may be taken to transplant if after induction therapy they remain with aplastic bone marrow and no morphological or flow-cytometry evidence of disease ≥ 28 days post-therapy. These high risk patients will be analyzed separately.
Burkitt's Lymphoma in CR2 or subsequent CR. Relapsed T-Cell Lymphoma that is chemotherapy sensitive in CR/PR that has failed or ineligible for an autologous transplantNatural Killer Cell Malignancies. Relapsed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone B-Cell Lymphoma or Follicular Lymphoma which have progressed within 12 months of achieving a partial or complete remission. Patients who had remissions lasting > 12 months, are eligible after at least two prior therapies. Patients with bulky disease should be considered for de-bulking chemotherapy before transplant. Patients with refractory disease may be eligible, unless bulky disease and an estimated tumor doubling time of less than one month.
Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphomais eligible after initial therapy if chemotherapy sensitive.
Large Cell and other high risk NHL > CR2/> PR2: Patients in CR2/PR2 with initial short remission (<6 months) are eligible.
Relapsed Multiple Myeloma: that is chemotherapy sensitive and has failed or ineligible for an autologous transplant.
Myeloproliferative Neoplasms/Myelofibrosis - with transfusion dependence or expected survival under 5 years by DIPSS, DIPSS-plus, or MPSS70 calculator.
Acquired Bone Marrow Failure Syndromes except for Fanconi anemia Other Leukemia Subtypes: A major effort in the field of hematology is to identify patients who are of high risk for treatment failure so that patients can be appropriately stratified to either more (or less) intensive therapy. This effort is continually ongoing and retrospective studies identify new disease features or characteristics that are associated with treatment outcomes. Therefore, if new features are identified after the writing of this protocol, patients can be enrolled with the approval of two members of the study committee.
Additional Criteria for Bulky Disease (lymphomas) if stable disease is best response, the largest residual nodal mass must < 5 cm (approximately) If response to previous therapy, the largest residual mass must represent a 50% reduction and be < 7.5 cm (approximately)
Organ Function Criteria
Adequate organ function is defined as:
Liver: Transaminases ≤ 5 x upper limit of normal (ULN) and total bilirubin ≤ 2.5 mg/dL except for patients with Gilbert's syndrome or hemolysis.
Renal: A normal creatinine (adults) or creatinine clearance ≥ 40 mL/min (pediatrics). Adults with a creatinine > 1.2 mg/dl or a history of renal dysfunction must have estimated GFR ≥ 40 ml/min/1.73m2.
Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction > 40%. For children that are not able to cooperate with MUGA and echocardiography, such should be clearly stated in the physician's note.
Pulmonary: DLCO, FEV1, FVC ≥ 40% predicted, and absence of O2 requirements. For children that are not able to cooperate with PFTs, a pulse oximetry with exercise should be attempted. If neither test can be obtained it should be clearly stated in the physician's note.
If recent confirmed mold infection (e.g. aspergillus) must have minimum of 30 days of therapy and responsive disease and be cleared by Infectious Disease HIV infection with undetectable viral load. All HIV+ patients must be evaluated by Infectious Disease (ID) and a HIV management plan establish prior to transplantation Sexually active females of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control during study treatment Voluntary written consent (adult or parent/guardian with presentation of the minor information sheet, if appropriate)
Related donors will be evaluated and collected according to UMN BMT program standard processes. Unrelated donors will be identified and collected through the National Marrow and Donor Program (NMDP) per usual steps.
Exclusion Criteria:
Pregnant or breast feeding. The agents used in this study include Pregnancy Category D: known to cause harm to a fetus. Females of childbearing potential must have a negative pregnancy test prior to starting therapy.
Untreated active infection
Active central nervous system malignancy
CML in blast crisis
Intermediate or high grade NHL, mantle cell NHL, and Hodgkin disease that is progressive on salvage therapy. Stable disease is acceptable to move forward provided it is non-bulky.
Less than 3 months since prior myeloablative transplant
Evidence of progressive disease by imaging modalities or biopsy - persistent PET activity, though possibly related to lymphoma, is not an exclusion criterion in the absence of CT changes indicating progression. Clinics and Surgery Center (CSC)
MT2023-10: A Phase 1 Study of FT522 in Combination with Rituximab in Participants with Relapsed/Refractory B-Cell Lymphoma
We are studying FT522 - a new product that is made by modifying cells in a laboratory - both with and without additional drugs, to see if it can help treat people with B-cell lymphoma. This study is for people who have had at least one treatment for their lymphoma, but the cancer either returned or did not respond to the treatment. We are testing this product to see what side effects it might have, as well as to see whether it is effective at treating B-cell lymphoma.
Veronika Bachanova, MD
SITE00001976
Clinics and Surgery Center (CSC)
MT2022-41 A Phase 1/2 Study Evaluating the Safety and Efficacy of a Single Dose of Autologous CD34+ Base Edited Hematopoietic Stem Cells (BEAM-101) in Patients with Sickle Cell Disease and Severe Vaso-Occlusive Crises (BEACON Trial) (BEACON)
To determine the safety and clinical efficacy of a single dose of autologous gene--edited CD34+ hematopoietic stem cell and progenitor cells (BEAM-101) in patients with severe SCD
Ashish Gupta
18 years to 35 years old
STUDY00017341
Key Inclusion Criteria Include:
Age ≥18 years to ≤35 years for the initial sentinel cohort; for subsequent enrollment patients from ≥12 years up to ≤35 years may be enrolled only upon approval by FDA.
Documented diagnosis of sickle cell disease with βS/βS, βS/β0, or βS/β+ genotypes.
Severe SCD defined by the occurrence of at least 4 severe VOCs in the 24 months prior to screening despite receiving hydroxyurea or other supportive care measures
Key Exclusion Criteria Include:
HbF levels >20%, obtained at the time of screening on or off hydroxyurea therapy
Previous receipt of an autologous or allogeneic HSCT or solid organ transplantation
Available and willing matched sibling donor
Definitive diagnosis of moyamoya syndrome based on screening brain MRA
History of overt stroke
Rare Diseases
Clinics and Surgery Center (CSC)
MT2022-45 Primary Immune Regulatory Disorders (PIRD): Longitudinal Study of Clinical Presentation, Treatment and Outcomes
The primary objective of this study is to estimate the overall survival (OS) of PIRD patients from the time of diagnosis. Patients may be treated with Best Available Therapy (BAT) or Hematopoietic Cell Transplant (HCT).
Christen Ebens
SITE00001766
Clinics and Surgery Center (CSC)
CANADIAN-AUSTRALASIAN RANDOMISED TRIAL OF SCREENING KIDNEY TRANSPLANT CANDIDATES FOR CORONARY ARTERY DISEASE (CARSK)
Cardiovascular disease is the most common cause of death while on the kidney transplant waiting list and after transplantation. Current standard care involves screening for coronary artery disease prior to waitlist entry, then every 1-2 years, according to perceived risk, until transplanted. The aim of screening is two-fold. Firstly, to identify patients with asymptomatic coronary disease to enable either correction, by bypass surgery or angioplasty, or removal of the patient from the list, with the ultimate aim of preventing premature cardiovascular mortality at the time of, or soon after, kidney transplantation. Secondly, from a societal perspective, to prevent mis-direction of scarce donor organs into recipients who experience early mortality. This current screening strategy is not evidence based, has substantial known and potential harms, and is very costly. Two major issues of uncertainty require addressing in sequence: (1) whether to periodically screen asymptomatic wait-listed patients for occult coronary artery disease; and (2) whether to revascularise coronary stenoses in asymptomatic patients prior to transplantation. The CARSK study seeks to address the first of these 2 issues.
Arthur Matas, MD
18 years and over
STUDY00018456
Inclusion Criteria:
adults aged 18 years of age or older
Dialysis-dependent kidney failure and currently being assessed for OR active on the kidney transplant waiting list
expected to require further screening for CAD prior to transplantation (by current standard of care);
able to give consent;
anticipated to undergo transplantation more than 12 months from date of enrolment
Exclusion Criteria:
patients with signs or symptoms suggestive of uncontrolled cardiac disease such as unstable coronary syndromes, decompensated heart failure, uncontrolled arrhythmia, and severe valvular heart disease;
patients who "on-hold" for transplantation due to a medical problem;
patients with other solid organ transplants;
multi-organ transplant candidates (e.g. kidney-pancreas transplant candidates);
patients with planned living donor transplant;
patients unable to give consent. Clinics and Surgery Center (CSC)
MT2021-01: PTCy + Sirolimus/VIC-1911 as GVHD prophylaxis in myeloablative PBSC transplantation
The primary objective of this study is to determine the optimal dose of VIC-1911 when given in combination with standard immunosuppressive therapy in adult patients undergoing myeloablative stem cell transplantation.
Shernan Holtan
18 years and over
STUDY00015049
Inclusion Criteria:
Diagnosis of
acute leukemia in complete remission, or
myelodysplasia with <5% blasts, or
myeloproliferative neoplasm/myelofibrosis with <5% marrow or circulating blasts
chemosensitive Hodgkin or non-Hodgkin lymphoma
Age 18 years or older
Performance status of ≥ 80% Karnofsky
Adequate organ function within 28 days of study registration defined as:
left ventricular ejection fraction ≥ 45%
pulmonary function with FEV1, FVC, and DLCO ≥ 50% predicted
AST and ALT < 2 times upper limit of normal
Total bilirubin <1.5 times the upper limit of normal. If the patient is suspected of having Gilbert syndrome, they require prior approval of the medical monitor
creatinine clearance ≥ 50cc/min
no active/uncontrolled infection
negative HIV, HBV and HCV
ferritin < 2000 ng/ml
Patients able to tolerate oral medication
Women of childbearing potential and men with partners of child-bearing potential must agree to use of contraception for the duration of treatment through 60 days after the last treatment of VIC-1911 or sirolimus
Able to provide written voluntary consent prior to the performance of any research related tests or procedures
Exclusion Criteria:
HCT-CI > 4 or unable to receive myeloablative TBI
Use of planned post-transplant maintenance therapy to begin prior to day +75. Patients may receive standard of care maintenance therapies starting at day
+75 or later
Patients with a history of hypersensitivity to any of the investigational products
Pregnant or breastfeeding as agents used in this study are Pregnancy Category
o C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations, and Pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. Females of childbearing potential must have a negative pregnancy test (serum or urine) within 28 days of study registration.
Women or men of childbearing potential unwilling to take adequate precautions to avoid unintended pregnancy from the start of protocol treatment through 60 days after the last treatment of VIC-1911 or sirolimus Clinics and Surgery Center (CSC)
MT2021-25: Phase I/II Multicenter study evaluating the Safety and Efficacy of Allogeneic GDA-201 Natural Killer cells in patients with relapsed/refractory B-Cell Non-Hodgkin Lymphoma
This study is designed to assess the safety of GDA-201 + rituximab, as well as the maximum tolerated dose in patients with B cell lymphomas in phase I; in phase II, it will assess safety and efficacy of GDA-201 in cohorts of patients with follicular lymphoma, high grade B cell lymphoma (including diffuse large B-cell), high grade B cell lymphoma not otherwise specified, and primary mediastinal B cell lymphoma.
Veronika Bachanova, MD
18 years and over
STUDY00015044
Inclusion Criteria:
Patients must have relapsed/refractory FL or HGBCL/DLBCL that has failed conventional therapy defined as follows:
Received at least 2 prior lines of therapy
Transplant ineligible patients allowed assuming they meet criterion a.
Patients who received prior chimeric antigen receptor modified T-cells (CAR-T) cell therapy or are considered ineligible for CAR-T therapy per the investigator's discretion
FL transformed to HGBCL: Must have received at least 1 line of therapy after transformation to DLBCL/HGBCL
Patients must be at least 18 years of age
Patients must have adequate hematologic, hepatic, renal, cardiac and pulmonary function prior to any study treatment.
Exclusion Criteria:
CNS lymphoma
Time between previous treatment and first dose of study treatment (rituximab):
Allogeneic HSCT < 6 months prior to study treatment
Autologous HSCT < 3 months prior to study treatment
CAR-T < 2 months prior to study treatment Clinics and Surgery Center (CSC)
A Phase I Study of HCW9218, a Bifunctional TGF-B; Antagonist/IL-15 Protein Complex, in Select Advanced Solid Tumors After Failing at Least Two Prior Therapies
This is an early study of a new drug, HCW9218, to treat certain solid tumors (except pancreatic cancer and brain tumors) that have not responded to usual treatment. People must have received at least two other types of treatment for the cancer. We are testing different doses of the drug to find the maximum dose that is tolerated.
Melissa Geller, MD
18 years and over
STUDY00015102
Inclusion Criteria:
• advanced/metastatic solid tumor cancer (except pancreatic and primary brain cancers)
• failed at least 2 prior lines of therapy given either in the recurrent or metastatic setting - refractory to or intolerant of existing therapy(ies)
• 18 years or older
• able to care for self and do light work
Exclusion Criteria:
• women who are pregnant or breast feeding
• tumor has spread to the brain
• history of medical or mental health issues (study staff will review)
Cancer
Clinics and Surgery Center (CSC)
MT2020-28: Ruxolitinib, Human Chorionic Gonadotropin (uhCG/EGF), and Dose De-escalated Corticosteroids for Treatment of Minnesota High-Risk Acute GVHD (aGVHD): A Phase I/II Study
The purpose of this study is to learn whether the use of Pregnyl with the drug ruxolitinib is able to reduce the need for high dose steroids to treat severe acute Graft versus Host Disease (GVHD).
Shernan Holtan
12 years and over
STUDY00014365
Inclusion Criteria:
HCT recipients over 12 years of age within the first 7 days of initial treatment of high-risk aGVHD, defined as:
Newly diagnosed Minnesota high-risk aGVHD -OR-
Newly diagnosed Minnesota standard risk aGVHD with plasma amphiregulin ≥ 33 pg/ml tested at the UMN Cytokine Reference Lab. For amphiregulin lab ordering information, see Fairview Lab Guide: http://labguide.fairview.org/showtest.asp?testid=6766&format=long -OR-
Newly diagnosed Minnesota standard risk aGVHD Ann Arbor 3 biomarkers tested by Viracor. For ordering information, see: https://www.viracor-eurofins.com/test-menu/403572p-agvhd-symptomatic- onset-algorithm/
Renal: Serum creatinine ≤2.5x upper limit of normal (ULN)
Cardiac: Left ventricular ejection fraction (LVEF) ≥ 35%
Voluntary written consent (adult or parent/guardian with minor assent for 12 through 17-year-olds).
Exclusion Criteria:
Progressive malignancy
Uncontrolled bacterial, fungal, parasitic, or viral infection at initiation of protocol treatment
Unwilling or unable to stop supplemental sex hormone therapy (estrogen, progesterone, and/or testosterone preparations)
Unwilling or unable to stop GnRH antagonists, aromatase inhibitors, or anti-androgens
History of a hormone responsive malignancy
Current thromboembolic disease requiring full-dose anticoagulation - patients receiving pharmacologic prophylaxis for thromboembolic disease will be eligible
Active or recent (within prior 3 months) thrombus, irrespective of anticoagulation status
Pregnancy
Women or men of childbearing potential unwilling to take adequate precautions to avoid unintended pregnancy from the start of protocol treatment through 30 days after the last treatment Clinics and Surgery Center (CSC)
A multicenter, single arm, open-label trial to evaluate efficacy and safety of oral, twice daily iptacopan in adult PNH patients who have Hb >=10 g/dL in response to anti-C5 antibody and switch to iptacopan
This is a multicenter, single-arm, open label trial, with iptacopan treatment for 24 weeks in adult PNH patients. Eligible participants must have a mean Hb ≥10 g/dL in response to a stable regimen with anti-C5 for at least 6 months and must be transfusion free for the same period.
Joan Beckman
STUDY00018020
Clinics and Surgery Center (CSC)
MT2013-31:Allogeneic Hematopoietic Cell Transplantation for Inherited Metabolic Disorders and Severe Osteopetrosis following Conditioning with Busulfan (Therapeutic Drug Monitoring), Fludarabine +/- ATG
To evaluate the ability to achieve high-level donor hematopoietic engraftment (defined as neutrophil recovery by Day +42 post-transplant and ≥ 80% donor cells on the myeloid fraction of peripheral blood at Day +100 post-transplant) using related and unrelated BM, PBSC, or UCB grafts following a reduced intensity conditioning regimen based on targeted-exposure busulfan, fludarabine +/- serotherapy in patients with inherited metabolic disorders and severe osteopetrosis.
Paul Orchard
Up to 55 years old
1406M51542
Inclusion Criteria:
0 through 55 years of age
Adequate graft available
Adequate organ function
Eligible Diseases:
Mucopolysaccharidosis Disorders:
MPS IH (Hurler syndrome)
MPS II (Hunter syndrome) if the patient has no or minimal evidence of symptomatic neurologic disease but is expected to have a neurologic phenotype
MPS VI (Maroteaux-Lamy syndrome)
MPS VII (Sly syndrome)
Glycoprotein Metabolic Disorders:
Alpha mannosidosis
Fucosidosis
Aspartylglucosaminuria
Sphingolipidoses and Recessive Leukodystrophies:
Globoid cell leukodystrophy
Metachromatic leukodystrophy
Niemann-Pick B patients (sphingomyelin deficiency)
Niemann-Pick C subtype 2
Peroxisomal Disorders:
Adrenoleukodystrophy with cerebral involvement
Zellweger syndrome
Neonatal Adrenoleukodystrophy
Infantile Refsum disease
Acyl-CoA-Oxidase Deficiency
D-Bifunctional enzyme deficiency
Multifunctional enzyme deficiency
Alpha-methylacyl-CoA Racmase Deficiency (AMACRD)
Mitochondrial Neurogastrointestingal Encephalopathy (MNGIE)
Severe Osteopetrosis (OP)
Hereditary Leukoencephalopathy with axonal spheroids (HDLS; CSF1R mutation)
Other Inherited Metabolic Disorders (IMD): Patients will also be considered who have other life-threatening, rare lysosomal, peroxisomal or other similar inherited disorders characterized by white matter disease or other neurologic manifestations for which there is rationale that transplantation would be of benefit, such as certain patients with Wolman's disease, GM1 gangliosidosis, I-cell disease, Tay-Sachs disease, Sandhoff disease or others.
Voluntary written consent
Exclusion Criteria:
Pregnancy - menstruating females must have a negative serum or urine pregnancy test within 14 days of study treatment start
Prior myeloablative chemotherapy exposure within 4 months of the start of conditioning on this protocol (patients excluded for this reason may be eligible for other institutional protocols)
Uncontrolled bacterial, fungal or viral infections including HIV (including active infection with Aspergillus or other mold within 30 days) Clinics and Surgery Center (CSC)
MT2021-11: An Open-label, Single-arm, Multicohort, Phase 2 Study to Assess the Efficacy and Safety of Tabelecleucel in Subjects with Epstein-Barr Virus-associated Diseases
This study is intended to determine the clinical benefit of tabelecleucel (EBV-specific cytotoxic T-lymphocytes) in subjects with EBV-associated diseases.
Joseph Maakaron
STUDY00013494
Inclusion Criteria:
Diagnosis of EBV+ disorder
Eastern Cooperative Oncology Group performance status <= 3 for participants aged >= 16 years; Lansky score >= 20 for participants from >=1 year to < 16 years
Adequate organ function test results, unless organ dysfunction is considered to be due to the underlying EBV-associated disease by the investigator
Cohort-specific Inclusion Criteria:
For participants with PID LPD:
R/R or newly diagnosed PID LPD for whom the standard first-line therapy is inappropriate, as determined by investigator. The LPD is confirmed by at least biopsy-proven EBV+ LPD or positive cerebrospinal fluid (CSF) cytology with or without radiographically measurable intracranial disease with EBV detected in CSF.
Participants with R/R disease must have had at least one prior line of systemic therapy and one of the following: radiographic disease progression per Lugano Classification (Cheson BD, et al. J Clin Oncol. 2014;27:3059) during or after treatment or failure to achieve a CR or partial response (PR) (defined by Lugano radiographic criteria) after standard first-line therapy
Participant may have systemic disease only, systemic and CNS disease, or CNS disease only
For participants with AID LPD:
R/R or newly diagnosed AID LPD for whom the standard first line therapy is inappropriate, as determined by the investigator. The LPD is confirmed by at least biopsy-proven EBV+ LPD or positive CSF cytology, with or without radiographically measurable intracranial disease, with EBV detected in CSF.
Participants with R/R disease must have had at least one prior line of systemic therapy and one of the following: radiographic disease progression per Lugano Classification during or after treatment or failure to achieve a CR or PR (defined by Lugano radiographic criteria) after standard first-line therapy
Participant may have systemic disease only, systemic and CNS disease, or CNS disease only
For participants with AID etiology or AID attributable to immunosenescence, objective laboratory evidence of immunodeficiency
For participants with CNS PTLD:
R/R or newly diagnosed EBV+ CNS PTLD for whom the standard first-line therapy is inappropriate, as determined by the investigator. The CNS PTLD is histologically confirmed by at least biopsy-proven EBV+ CNS PTLD or positive CSF cytology with or without radiographically measurable intracranial disease with EBV detected in CSF.
Participants with R/R disease must have had at least one prior line of systemic therapy and one of the following: radiographic disease progression per Lugano Classification during or after treatment or failure to achieve a CR or PR (defined by Lugano radiographic criteria) after standard first-line therapy
Participant may have systemic and CNS disease or CNS disease only
For participants with EBV+ PTLD, including CD20-negative disease:
Biopsy-proven EBV+ PTLD for whom standard first-line therapy (rituximab and/or chemotherapy) is inappropriate, as determined by the investigator
Participants must have systemic disease measurable per Lugano Classification criteria, except when contraindicated or mandated by local practice, then MRI may be used
For participants with sarcoma, including LMS, or smooth muscle tumors:
EBV+ sarcoma or smooth muscle tumor with rapidly progressive disease defined as progressive disease per RECIST 1.1 criteria as documented radiographically within a 6-month interval prior to enrollment
Participants with newly diagnosed EBV+ sarcoma for whom the standard first-line therapy is inappropriate, as determined by the investigator
Biopsy-proven EBV+ sarcoma meeting one of the criteria's of pathologically confirmed EBV+ Leiomyosarcoma or EBV+ sarcoma or smooth muscle tumor
Measurable disease using diagnostic CT and/or MRI following RECIST 1.1 criteria (Eisenhauer et al. 2009. Eur J Cancer 45[2]:228-247)
Exclusion Criteria:
Currently active Burkitt, T-cell, natural killer/T-cell lymphoma/LPD, Hodgkin, plasmablastic, transformed lymphoma, active hemophagocytic lymphohistiocytosis, or other malignancies requiring systemic therapy
Serious known active infections, defined as ongoing uncontrolled adenovirus infection or infections requiring systemic therapy at the time of enrollment, or known history of human immunodeficiency virus (HIV) infection
Suspected or confirmed Grade >= 2 acute graft-versus-host disease (GvHD) per the Center for International Blood and Marrow Transplant Research (CIBMTR) consensus grading system or extensive chronic GvHD per National Institutes of Health (NIH) consensus criteria at the time of the enrollment
Need for vasopressor or ventilatory support at the time of enrollment
Prior therapy (in order of increasing washout period) prior to enrollment as follows:
Within 4 weeks or 5 half-lives (whichever is shorter) for any investigational product and/ or any chemotherapy (systemic or intrathecal), targeted small molecule therapy, or antibody/biologic therapy. Note: prior anti-CD20 antibody use is permitted within the washout period if a subsequent disease response assessment indicates disease progression
Within 8 weeks: prior tabelecleucel (>8 weeks prior to enrollment) is permitted if response was obtained or if usual protocol-directed therapeutic options were not exhausted, for cellular therapies (chimeric antigen receptor therapies directed at T-cells or T-cell subsets, donor lymphocyte infusion, other CTLs or virus-specific T-cells); and/or therapies which could impact tabelecleucel function (anti-thymocyte globulin, alemtuzumab)
Any prior treatment with EBV-CTLs with the exception of tabelecleucel as above
Women who are breastfeeding or pregnant
Unwilling to comply with protocol specified contraceptive/reproductive restrictions from enrollment through 90 days after the last treatment
Ongoing need for daily steroids of > 0.5 mg/kg prednisone or glucocorticoid equivalent, ongoing methotrexate, or extracorporeal photopheresis (for participants with CNS disease, protocol-specified dexamethasone is permitted and concludes by the time of enrollment)
Any conditions that may put the study outcomes at undue risk (life expectancy < 60 days or any life-threatening illness, medical condition, or organ system dysfunction)
For participants with PID LPD or AID LPD: history of prior allogeneic HCT or solid organ transplant
For participants with EBV+ PTLD: prior systemic therapy for PTLD Clinics and Surgery Center (CSC)
MT2017-45 :Chimeric Antigen Receptor (CAR)-T Cell Therapy for Patients with Hematologic Malignancies
This is a phase II study of FDA-approved CAR-T products for patients with hematologic malignancies. The study provides criteria for consistent treatment and management according to FDA labelling of CAR-T products and does not contain experimental components. Patients will be assigned to Arms A B and C based on age, CAR-T product and diagnosis. Overall remission rate, safety events and other endpoints will be calculated for Arms A B and C separately.
Veronika Bachanova, MD
STUDY00004096
ARM A (Kymriah) and Arm G (Tecartus) :Refractory/relapsed B-cell acute lymphoblastic leukemia expressing CD19
Inclusion Criteria:
Age and Disease Status
Must be age 0-25 years (for Arm A Kymriah) or >18 years (Arm G Tecartus)
Disease status: Relapsed and refractory pediatric B-cell ALL defined by one of these:
Primary induction failure with no complete remission after ≥2 cycles of induction chemotherapy, or
Patients with persistent minimal residual disease (MRD >0.01% by flow cytometry or persistent by cytogenetic or molecular assays) after ≥2 cycles of consolidation chemotherapy, or
Patients in 2nd or greater relapse of B-ALL or
Patients with persistent CNS leukemia, or
Down Syndrome or other congenital diseases assuming that they fit the criteria for second or greater relapse or refractory leukemia, or
Patients with Ph+ ALL are eligible if theywho have failed or are intolerant to two lines of TKI assuming they fit the criteria for second or greater relapse or are considered refractory.
Performance Status
* Arm A: Karnofsky (age ≥16 years) or Lansky (age < 16 years) performance status ≥ 50% at screening; Arm G: ECOG 0, 1 or 2
Organ Function
Renal function defined as:
A serum creatinine of ≤1.5 x ULN OR
eGFR ≥ 50 mL/min/1.73 m2
Liver function defined as:
** ALT ≤ 5 times the ULN for age (unless due to disease)
** Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
Other Inclusion Criteria
Life expectancy ≥12 weeks
Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
Exclusion Criteria:
Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
Patients with Burkitt's lymphoma/leukemia (i.e. patients with mature B-cell ALL, leukemia with B-cell [sIg positive and kappa or lambda restricted positivity] ALL, with FAB L3 morphology and /or a MYC translocation)
CNS 2A
CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
Uncontrolled active hepatitis B or hepatitis C
Active HIV infection
Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
Intolerance to the excipients of the CAR-T cell product
Any immunosuppressive medication must be stopped ≥ 2 weeks prior to enrollment.
Patient has taken one of the prohibited concomitant medications within the timeframe outlined in section 6.1
ARM B: Yescarta for Relapsed or Refractory diffuse large B cell lymphoma
Inclusion Criteria:
Age and Disease Status
Adult patients (age ≥ 18 years)Patients must be ≥18 years of age
One of the following histologies and expression of CD19 by tumor cells:
** diffuse large B-cell lymphoma (DLBCL) not otherwise specified, or
** primary mediastinal large B-cell lymphoma, or
** high grade B-cell lymphoma, or
** DLBCL arising from follicular lymphoma
Disease status:
** Chemotherapy refractory disease after ≥2 lines of chemotherapy, or
** Relapsed with no remission after ≥1 lines of salvage chemotherapy, or
** Relapsed following autologous HCT (and failed at least 2 prior lines of therapy including high dose chemotherapy). If salvage therapy is given post autoHCT, the subject must have no response or relapse after the last line of therapy
Measurable disease at time of apheresis: Nodal lesions or extranodal lesion
ECOG performance status 0-2
ALC >/=100/uL at screening (prior to apheresis)
Renal function defined as:
** A serum creatinine of ≤1.5 x ULN OR
** eGFR ≥ 50 mL/min/1.73 m2
Liver function defined as:
ALT ≤ 5 times the ULN for age (unless due to disease)
Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as :
Absolute neutrophil count (ANC) > 1.000/mm3 (only for NHL)
Platelets ≥ 50.000/mm3 (transfusion support can be provided)
Hemoglobin >8.0 mg/dl (transfusion support can be provided)
Life expectancy ≥12 weeks
Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
Exclusion Criteria:
Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
Uncontrolled active hepatitis B or hepatitis C
Active HIV infection (controlled HIV is permissible)
Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
Intolerance to the excipients of the CAR-T cell product
Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis.
Patient has taken one of the prohibited concomitant medications within the timeframe.
ARM C: Kymriah for rRelapsed or rRefractory diffuse large B cell lymphoma
Inclusion Criteria:
Age and Disease Status
Adult patients (age ≥ 18 years)
with relapsed or refractory (r/r) large B-cell lymphoma, including
diffuse large B-cell lymphoma (DLBCL) not otherwise specified,
high grade B-cell lymphoma
and DLBCL arising from follicular lymphoma.
Disease status:
after two or more lines of systemic therapy or
relapse after autologous HCT
Performance Status
ECOG performance status 0-2
ALC >/=100/uL at screening (prior to apheresis)
Organ Function
Renal function defined as:
A serum creatinine of ≤1.5 x ULN OR
eGFR ≥ 50 mL/min/1.73 m^2
Liver function defined as:
ALT ≤ 5 times the ULN for age (unless due to disease)
Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as :
Absolute neutrophil count (ANC) > 1.000/mm3 (only for NHL)
Platelets ≥ 50.000/mm3 (transfusion support can be provided)
Hemoglobin >8.0 mg/dl (transfusion support can be provided)
Other Inclusion Criteria
Life expectancy ≥12 weeks
Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
Exclusion Criteria:
Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
Uncontrolled active hepatitis B or hepatitis C
Active or inactive HIV infection
Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
Intolerance to the excipients of the CAR-T cell product
Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis.
Patient has taken one of the prohibited concomitant medications within the timeframe
ARM D: Tecartus (Brexucabtagene Autoleucel) for relapsed or refractory mantle cell lymphoma
Inclusion Criteria:
Age and Disease Status
* with relapsed or refractory (r/r) mantle cell lymphoma, including
prior anthracycline or Bendamustine containing therapy
prior Rituximab or other CD20 directed antibody (or inability to treat with CD20 MoAb)
not a candidate or relapse after autologous HCT
active disease at enrollment
Performance Status
*ECOG performance status 0-1
Organ Function
Renal function defined as:
A serum creatinine of ≤1.5 x ULN OR
eGFR ≥ 50 mL/min/1.73 m2
Liver function defined as:
ALT ≤ 5 times the ULN for age (unless due to disease)
Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as:
Absolute neutrophil count (ANC) > 1,000/mm^3 (only for NHL)
Platelets ≥ 50,000/mm^3 (transfusion support can be provided)
Hemoglobin >8.0 mg/dl (transfusion support can be provided)
Other Inclusion Criteria:
Life expectancy ≥12 weeks
Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment. See section 4.5 for definitions of child bearing potential and section 4.6 for definitions of adequate birth control.
Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
Exclusion Criteria:
Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
Uncontrolled active hepatitis B or hepatitis C
Active HIV infection
Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
Intolerance to the excipients of the CAR-T cell product
Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis (steroids must be stopped >72 hours prior to apheresis).
Patient has taken one of the prohibited concomitant medications within the timeframe
ARM E: Breyanzi "lisocabtagene maraleucel" for relapsed or refractory large B-cell lymphoma
Inclusion Criteria:
Age and Disease Status
Adult patients (age ≥ 18 years)
with relapsed or refractory disease after two or more lines of systemic therapy, including
diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma),
high-grade B-cell lymphoma,
primary mediastinal large B-cell lymphoma,
follicular lymphoma grade 3B
Performance Status
*ECOG performance status 0-2
Organ Function
Renal function defined as:
A serum creatinine of ≤1.5 x ULN OR
eGFR ≥ 30 mL/min/1.73 m2
Liver function defined as:
ALT ≤ 5 times the ULN for age (unless due to disease)
Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
Hemodynamically stable and LVEF ≥ 40% confirmed by echocardiogram or MUGA
Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as:
Absolute neutrophil count (ANC) > 1,000/mm^3 (only for NHL)
Platelets ≥ 50,000/mm^3 (transfusion support can be provided)
Hemoglobin >8.0 mg/dl (transfusion support can be provided)
Other Inclusion Criteria:
Life expectancy ≥12 weeks
Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment. See section 4.5 for definitions of child bearing potential and section 4.6 for definitions of adequate birth control.
Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
Exclusion Criteria:
Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
Uncontrolled active hepatitis B or hepatitis C
Active HIV infection
Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
Intolerance to the excipients of the CAR-T cell product
Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis (steroids must be stopped >72 hours prior to apheresis).
Patient has taken one of the prohibited concomitant medications within the timeframe
ARM F: Abecma "Idecabtagene Vicleucel" for relapsed or refractory multiple myeloma
Inclusion Criteria:
Age and Disease Status
Adult patients (age ≥ 18 years)
Relapsed (progression after prior partial or complete remission) or refractory multiple myeloma
Evidence of active disease (medullary or extramedullary)
Prior therapy (Failure or intolerance to) with an immunomodulatory agent, a proteasome inhibitor, and an antiCD38 monoclonal antibody
Performance Status
*ECOG performance status 0-1
Organ Function
Renal function defined as:
A serum creatinine of ≤2 x ULN OR
eGFR ≥ 50 mL/min/1.73 m2
Liver function defined as:
ALT ≤ 5 times the ULN for age (unless due to disease)
Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as:
Absolute neutrophil count (ANC) > 1,000/mm^3 (only for NHL)
Platelets ≥ 50,000/mm^3 (transfusion support can be provided)
Hemoglobin >8.0 mg/dl (transfusion support can be provided)
Other Inclusion Criteria:
Life expectancy ≥12 weeks
Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment. See section 4.5 for definitions of child bearing potential and section 4.6 for definitions of adequate birth control.
Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
Exclusion Criteria:
Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
Uncontrolled active hepatitis B or hepatitis C
Active HIV infection
Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
Intolerance to the excipients of the CAR-T cell product
Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis (steroids must be stopped >72 hours prior to apheresis).
Patient has taken one of the prohibited concomitant medications within the timeframe Clinics and Surgery Center (CSC)
MT2016-11 :Autologous Stem Cell Transplant In Patients with Hodgkin Lymphoma (HL) and Non-Hodgkin Lymphomas (NHL)
Veronika Bachanova, MD
Up to 75 years old
1611M99805
Inclusion Criteria:
Eligible Diseases
Non-Hodgkin's Lymphoma (NHL)
Patients with chemo-sensitive histologically confirmed NHL will be eligible for this treatment protocol contingent on histologic sub-classification.
Patients in partial or complete remission following cell therapy will also be eligible.
NHL patients with resistant or refractory lymphoma (no PR following up to three cycles of combination chemotherapy) will not be eligible for transplant in this trial.
Lymphoblastic Lymphoma:
All patients will be eligible in second or greater complete remission (CR) or first or subsequent partial remission (PR)
Patients with any high-risk features will be eligible in first complete remission
High risk features include: Stage IV, LDH >2 x upper limit of normal, ≥ 2 extranodal sites
Mature B-cell Lymphoma
Follicular Lymphoma and other indolent lymphoma in ≥ second CR2/PR2
Diffuse Large B-Cell Lymphoma: in ≥ CR2 or ≥ PR1; a high intermediate or high IPI (≥ 2 for age-adjusted IPI or ≥3 for IPI) at diagnosis and double-hit or triple-hit lymphoma will be eligible in first CR; transformed lymphoma from FL (or other indolent lymphoma) or chronic lymphocytic leukemia will be eligible if chemosensitive and bone marrow is negative
Mantle Cell Lymphoma: in first or greater CR or PR
Burkitt's/Burkitt's like: all patients except localized lymphoma will be eligible any time after initial therapy (after achievement of first complete remission), or in partial remission if they fail to achieve CR; patients with localized (stage I or Ziegler stage A) will be eligible only if they fail to achieve CR1 or after relapse
Mature T-Cell Lymphoma
Chemosensitive T-cell lymphomas including Primary T-cell not otherwise specified angioimmunoblastic, and ALK-positive anaplastic large cell, will be eligible after initial therapy, whether or not CR is achieved.
Mycosis fungoides/Sezary syndrome will be eligible in ≥CR2/PR2
Hodgkin Lymphoma (HL)
Patients with histologically proven HL will be eligible for transplantation after failing prior therapy.
Patients with resistant disease (initial or at relapse): those who fail to achieve an objective partial response to three cycles of combination non-cross resistant chemotherapy will not be eligible for transplant in this trial.
For stage I/II patients treated with primary chemotherapy-radiation, they must have failed (no CR or progression after CR) at least one salvage combination chemotherapy treatment regimen
For advanced (stage III/IV) Hodgkin disease, patients must have failed an Adriamycin containing regimen (ABVD) or an alternative non-cross resistant regimen (e.g. MOPP)
Patients with any high-risk features will also be eligible, including those who:
fail to achieve complete remission with initial combination chemotherapy
have bulky disease after initial therapy (chemotherapy or radiation) defined as residual mediastinal mass ≥ 5 cm or other residual mass ≥ 10 cm accompanied by other features of persisting disease (e.g., PET scan positive; high LDH; enlarging on serial x-rays or biopsy positive) will be eligible - if feasible, persistent disease should be proven by biopsy
Patients should receive chemotherapy to attempt to achieve CR or minimal disease state for all patients pre-transplantation. The use of up to three cycles of non-cross resistant combination chemotherapy is advised.
Residual areas of limited disease should be considered for radiotherapy after and not prior to transplantation.
HIV positive patients who are otherwise eligible for this study may be enrolled if they meet the following requirements:
Are seen in the infectious disease (ID)/HIV clinic prior to enrollment on study for the purpose of determining eligibility and for local coordination of HIV care during the peri-transplant period.
Are on maximally active anti-HIV regimen to control disease as determined appropriate by the ID/HIV physicians. For the majority of patients, this will be a highly active anti-retroviral therapy (HAART)-type therapy including a protease inhibitor.
CD4+ ≥ 50/µL
HIV RNA viral load ≤ 100,000 copies per mL on each of samples 4 weeks apart. The most recent level must be within 30 days of enrollment.
Performance Status: Karnofsky Performance Status ≥ 80% for patients ≥ 16 years of age or Lansky Play Score ≥ 80 for patients < 16 years of age. Note: if poor performance status is due to lymphoma - KPS ≥ 60% or LPS ≥ 60 is acceptable
Organ Function
• No evidence of serious organ dysfunction that is not attributable to tumor including: Hematologic: hemoglobin > 8 gm/dL WBC > 2.5 x 109/L with an ANC > 1.5 x 109/L off G-CSF or GM-CSF for 10 days or Neulasta for 21 days platelets > 100 x 109/L without transfusion bone marrow cellularity of > 20% with <5% involvement with tumor Renal: GFR > 50 ml/min/1.73m2 or serum creatinine ≤ 2.5 x ULN for age Hepatic: no history of severe prior or ongoing chronic liver disease. Total bilirubin ≤ 2.0 mg/dl, AST and alkaline phosphatase <5x upper limit of normal Cardiac: free of symptoms of uncontrolled cardiac disease including unstable angina, decompensated congestive heart failure, or arrhythmia. The ejection fraction by gated cardiac blood flow scan (MUGA) or Echocardiogram must be >40% Pulmonary: no significant obstructive airways disease (FEV1 must be ≥ 50%) and must have acceptable diffusion capacity (corrected DLCO > 50% of predicted) Central Nervous System: Patients with a history of CNS involvement by lymphoma or with relapsed primary CNS lymphoma will be eligible for Cy/TBI arm. Patients with active CNS disease are eligible if they have completed a standard treatment for CNS lymphoma and have no evidence of progressive CNS disease at the time of enrollment Other Inclusion Criteria At least 4 weeks from previous chemotherapy; 6 weeks from nitrosoureas Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment Patients who are carriers of Hepatitis B will be included in this study Voluntary written consent
Exclusion Criteria:
Pregnant or breastfeeding: Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy
Eligible for any higher priority transplant protocols
Chemotherapy resistant disease
Unrelated active infection Clinics and Surgery Center (CSC)
MT2014-10C : Allogeneic Hematopoietic Stem Cell Transplant for Patients with High Risk Hemoglobinopathies and Other Red Cell Transfusion Dependent Disorders
Ashish Gupta
Up to 55 years old
1407M52125
Inclusion Criteria:
Diagnosis of Sickle Cell Disease, Thalassemia, Diamond Blackfan Anemia or other non-malignant hematologic disorders for which a stem cell transplant is indicated
Acceptable stem cell source identified
Performance status of ≥ 70% (Karnofsky),or ≥ 70 (Lansky play score)
Creatinine <2.0 mg/dl for adults or glomerular filtration rate > 50 ml/min for children
Bilirubin, Aspartate Aminotransferase, Alkaline phosphatase <5 times the upper limit of institutional normal
Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction > 40%
Exclusion Criteria:
active, uncontrolled infection
pregnant or breastfeeding
HIV positive Clinics and Surgery Center (CSC)
MT2013-34C: Hematopoietic Stem Cell Transplant for Dyskeratosis Congenita or Severe Aplastic Anemia: Standard of Care Considerations
Christen Ebens
0 years to 70 years old
1404M50183
Inclusion Criteria:
Aged 0 - 70 years
Acceptable hematopoeitic stem cell donor
Dyskeratosis Congenita (DC) with evidence of BM failure defined as:
requirement for red blood cell and/or platelet transfusions or
requirement for G-CSF or GM-CSF or erythropoietin or
refractory cytopenias having one of the following three
platelets <50,000/uL or transfusion dependent
absolute neutrophil count <500/uL without hematopoietic growth factor support
hemoglobin <9g/uL or transfusion dependent
Diagnosis of DC with a triad of mucocutaneous features:
oral leukoplakia
nail dystrophy
abnormal reticular skin hyperpigmentation, or
Diagnosis of DC with one of the following:
short telomeres (under a research study)
mutation in telomerase holoenzyme (DKC1, TERT, TERC, NOP10, NHP2, TCAB1)
mutation in shelterin complex (TINF2)
mutation in telomere-capping complex (CTC1)
Severe Aplastic Anemia (SAA) primary transplant with evidence of BM failure:
Refractory cytopenia defined by bone marrow cellularity <50% (with < 30% residual hematopoietic cells)
Diagnosis of SAA with refractory cytopenias having one of the following three:
platelets <20,000/uL or transfusion dependent
absolute neutrophil count <500/uL without hematopoietic growth factor support
absolute reticulocyte count <20,000/uL
Severe Aplastic Anemia (SAA) requiring a 2nd transplant
Graft failure as defined by blood/marrow chimerism of < 5%
Early myelodysplastic features
With or without clonal cytogenetic abnormalities
Adequate organ function defined as:
cardiac: left ventricular ejection fraction ≥ 35% with no evidence of decompensated heart failure
pulmonary: DLCO ≥30% predicted, no supplemental oxygen requirement
renal: Glomerular filtration rate (GFR) ≥30% predicted
Voluntary written consent
Exclusion Criteria:
Acute hepatitis or evidence of moderate or severe portal fibrosis or cirrhosis on biopsy
Pregnant or lactating
Uncontrolled infection
Prior radiation therapy (applies to SAA patients only)
Diagnosis of Fanconi anemia based on DEB
Diagnosis of dyskeratosis congenita with advanced MDS or acute myeloid leukemia with >30% blasts Clinics and Surgery Center (CSC)
MT2013-09C : Umbilical Cord Blood Transplantation Using a Myeloablative Preparative Regimen for the Treatment of Hematological Diseases
This is a treatment protocol for an unrelated umbilical cord blood transplant (UCBT) using a myeloablative preparative regimen for the treatment of hematological diseases, including, but not limited to acute leukemias. There is no research element except the collection of routine clinical data.
Margaret MacMillan, MD
Up to 55 years old
1305M34181
Inclusion Criteria:
Eligible Disease Status
Acute Myeloid Leukemia (AML): high risk CR1 (as evidenced by preceding MDS, high risk cytogenetics, ≥ 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia; CR2+. All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
Very high risk pediatric patients with AML: Patients <21 years, however, are eligible with (M2 marrow) with < 25% blasts in marrow after having failed one or more cycles of chemotherapy.
Acute Lymphocytic Leukemia (ALL): high risk CR1 as defined by cytogenetics (such as t(9;22), t (1:19), t(4;11), other MLL rearrangements, hypodiploidy, or IKZF1 abnormalities), DNA index < 0.81, > 1 cycle to obtain CR or presence minimal residual disease (MRD). Patients in CR2+ are eligible. All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
Very high risk pediatric patients with ALL: patients <21 years are also considered high risk CR1 if they had M2 or M3 marrow at day 42 from the initiation of induction or M3 marrow at the end of induction. They are eligible once they achieved a complete remission.
Chronic Myelogenous Leukemia excluding refractory blast crisis: To be eligible in first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate.
Plasma Cell Leukemia after initial therapy, who achieved at least a partial remission
Advanced Myelofibrosis
Myelodysplasia (MDS) IPSS INT-2 or High Risk (i.e. RAEB, RAEBt) or Refractory Anemia with severe pancytopenia or high risk cytogenetics: Blasts must be < 10% by a representative bone marrow aspirate morphology.
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone B-Cell Lymphoma or Follicular Lymphoma are eligible if there was disease progression/relapse within 12 of achieving a partial or complete remission. Patients who had remissions lasting > 12 months, are eligible after at least two prior therapies. Patients with bulky disease (nodal mass greater than 5 cm) should be considered for de-bulking chemotherapy before transplant.
Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia are eligible after initial therapy in CR1+ or PR1+.
Large Cell NHL > CR2/> PR2: Patients in CR2/PR2 with initial short remission (<6 months) are eligible.
Lymphoblastic Lymphoma, Burkitt's Lymphoma, and other high-grade NHL after initial therapy if stage III/IV in CR1/PR1 or after progression if stage I/II < 1 year.
Multiple Myeloma beyond PR2: Patients with chromosome 13 abnormalities, first response lasting less than 6 months, or β-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy.
Myeloproliferative Syndromes
Availability of suitable UCB unit(s)
0 to 55 years
Voluntary written consent (adult or parental/guardian)
Exclusion Criteria:
previous irradiation that precludes the safe administration of TBI - Radiation Oncology will evaluate all patients who have had previous radiation therapy
chemotherapy refractory large cell and high grade NHL (ie progressive disease after > 2 salvage regimens)
if ≤ 18 years old, prior myeloablative transplant within the last 6 months. If >18 years old prior myeloablative allotransplant or autologous transplant
extensive prior therapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation
pregnant or breastfeeding
HIV positive Clinics and Surgery Center (CSC)
MT2013-06C : Treatment of graft Failure after HSCT
Troy Lund
1404M49341
Inclusion Criteria:
Patients with primary or secondary graft failure, as defined below, may receive a second transplant:
Primary graft failure is defined as not achieving an ANC ≥0.5x10^9/L for three consecutive days by day 35 - 42 following the first transplant.
Secondary graft failure is defined as achieving an ANC ≥0.5x10^9/L for three consecutive days by day 35 - 42, but subsequently drops below 0.5x10^9/L without recovery.
Loss of chimerism is defined as achieving an ANC ≥0.5x10^9/L for three consecutive, but with less than 10% CD15+ donor cells in the marrow or peripheral blood.
Recipients should have acceptable organ function defined as:
Renal: creatinine < 2.0 (adults) and creatinine clearance > 30. For creatinine clearance < 70, consultation with a BMT pharmacist is necessary for chemotherapy dose adjustments.
Hepatic: bilirubin, AST/ALT, ALP < 10 x upper limit of normal
Cardiac: left ventricular ejection fraction > 40%
Exclusion Criteria:
Uncontrolled infection at the time of transplant.
Patients with Fanconi Anemia or other DNA breakage syndromes. Clinics and Surgery Center (CSC)
MT2012-10C: Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
Christen Ebens
Up to 50 years old
1207M17321
Inclusion Criteria:
Diagnosis of immunodeficiency or histiocytic disorder including the following:
Severe combined immunodeficiency (SCID - all variants)
Second bone marrow transplant (BMT) for SCID (after graft rejection)
Omenn's Syndrome
Reticular dysgenesis
Wiskott-Aldrich syndrome
Major histocompatibility complex (MHC) Class II deficiency (bare lymphocyte syndrome)
Hyper IgM Syndrome (CD40 Ligand Deficiency)
Common variable immunodeficiency (CVID) with severe phenotype
Chronic Granulomatous Disease (CGD)
Other severe Combined Immune Deficiencies (CID)
Hemophagocytic Lymphohistiocytosis (HLH)
X-linked Lymphoproliferative Disease (XLP)
Chediak-Higashi Syndrome (CHS)
Griscelli Syndrome
Langerhans Cell Histiocytosis (LCH)
Acceptable stem cell sources include:
HLA identical or 1 antigen matched sibling donor eligible to donate bone marrow
HLA identical or up to a 1 antigen mismatched unrelated BM donor
Sibling donor cord blood with acceptable HLA match and cell dose as per current institutional standards
Single unrelated umbilical cord blood unit with 0-2 antigen mismatch and minimum cell dose of >5 x 10^7 nucleated cells/kg as per current institutional guidelines
Double unrelated umbilical cord blood units that are:
up to 2 antigen mismatched to the patient
up to 2 antigen mismatched to each other
minimum cell dose of at least one single unit must be ≥ 3.5 x 10^7 nucleated cells/kg
combined dose of both units must provide a total cell dose of ≥ 5 x 10^7 nucleated cells/kg
Age: 0 to 50 years
Adequate organ function and performance status.
Exclusion Criteria
pregnant or breastfeeding
active, uncontrolled infection and/or HIV positive
acute hepatitis or evidence of moderate or severe portal fibrosis or cirrhosis on biopsy Clinics and Surgery Center (CSC)
MT2011-09C Alkylator-Intense Conditioning Followed By Autologous Transplantation for Patients with High Risk or Relapsed Solid or CNS Tumors
Treatment guidelines for high risk or relapsed solid tumors consisting of a busulfan, melphalan, thiotepa conditioning followed by an autologous peripheral blood stem cell transplant and, if appropriate, disease specific radiation therapy at day 60+
Ashish Gupta
Up to 70 years old
1107M02641
Inclusion Criteria:
All patients must have histological verification of malignancy at original diagnosis.
Eligible Diseases
Arm A: Solid Tumor
Ewing's Family Tumors (ES/PNET/DSRCT) - metastatic at time of diagnosis and/or relapsed after therapy
Renal Tumors - relapsed (all histology - Wilm's tumor) or at diagnosis (clear cell sarcoma and Rhabdoid tumor)
Hepatoblastoma - metastatic at time of diagnosis and/or relapsed after therapy
Rhabdomyosarcoma - metastatic at time of diagnosis and/or relapsed after therapy
Soft Tissue Sarcoma - chemotherapy responsive metastatic disease or chemotherapy responsive relapsed disease
Primary Malignant Brain Neoplasms <18 years of age - at diagnosis and/or relapse
Retinoblastoma - disseminated at diagnosis and/or relapsed
CNS Lymphoma - primary or secondary CNS lymphoma.
Other High Risk Metastatic or Relapsed Solid Tumors - to be approved by 2 or more pediatric hematology/oncology and bone marrow transplant (BMT) physicians
Arm B: Certain CNS tumors
Medulloblastoma: Children less than 36 months (3 years) of age at time of definitive surgery (for histopathologic diagnosis) who have high risk Medulloblastoma, defined as any one of the following:
> 1.5 cm2 residual disease following resection for any Medulloblastoma histology
lumbar CSF cytology positive for tumor cells by analysis of fluid collected either before definitive surgery or at least 10 days after definitive surgery
MRI evidence of (a) gross nodular seeding in the intracranial subarachnoid space or ventricular system distant from primary tumor site, M2; or (b) gross nodular seeding in the spinal subarachnoid space +/- evidence of intracranial seeding, M3; or (c) extraneural metastases, M4,
Anaplastic Histologic Variant Medulloblastoma: less than 70 years of age, any metastatic stage, with total or sub-total resection.
Infant Medulloblastoma: Children less than 8 months of age at the time of definitive surgery (for histopathologic diagnosis), any histology, any metastatic state, with total or sub-total resection.
Supra-tentorial Primative Neuro-Ectodermal Tumor (PNET): Children less than 36 months (3 years) of age at time of definitive surgery (for histopathologic diagnosis) with or without metastatic disease
Atypical Teratoid/Rhabdoid Tumor (AT/RT): less than 70 years of age with CNS AT/RT (with or without metastatic disease).
Other High Risk CNS Tumors - to be approved by 2 or more physicians (at least one oncologist and one BMT physician).
Arm C: Germ Cell Tumors
Confirmation of germ cell tumor (GCT) histology (both seminoma and nonseminoma). Tumor may have originated in any primary site. NOTE: In rare circumstances, patients will be allowed to enroll even if a pathologic diagnosis may not have been established. This would require a clinical situation consistent with the diagnosis of GCT (testicular, peritoneal, retroperitoneal or mediastinal mass, elevated tumor marker levels {HCG ≥ 500; AFP ≥ 500} and typical pattern of metastases).
One or more unfavorable prognostic features for achieving a CR with conventional-dose chemotherapy. Unfavorable prognostic features include:
extragonadal primary site
PD following an incomplete response (IR) to first-line therapy,
PD after a conventional-dose salvage (cisplatin + ifosfamide -based) regimen
Arm D: Certain CNS Tumor patients who can only undergo one transplant
Medulloblastoma: Children less than 36 months (3 years) of age at time of definitive surgery (for histopathologic diagnosis) who have high risk Medulloblastoma, defined as any one of the following:
> 1.5 cm2 residual disease following resection for any Medulloblastoma histology
lumbar CSF cytology positive for tumor cells by analysis of fluid collected either before definitive surgery or at least 10 days after definitive surgery
MRI evidence of (a) gross nodular seeding in the intracranial subarachnoid space or ventricular system distant from primary tumor site, M2; or (b) gross nodular seeding in the spinal subarachnoid space +/- evidence of intracranial seeding, M3; or (c) extraneural metastases, M4,
Anaplastic Histologic Variant Medulloblastoma: less than 70 years of age, any metastatic stage, with total or sub-total resection.
Infant Medulloblastoma: Children less than 8 months of age at the time of definitive surgery (for histopathologic diagnosis), any histology, any metastatic state, with total or sub-total resection.
Supra-tentorial Primative Neuro-Ectodermal Tumor (PNET): Children less than 36 months (3 years) of age at time of definitive surgery (for histopathologic diagnosis) with or without metastatic disease
Atypical Teratoid/Rhabdoid Tumor (AT/RT): less than 70 years of age with CNS AT/RT (with or without metastatic disease).
Other High Risk CNS Tumors including choroid plexus carcinoma in children- to be approved by 2 or more physicians (at least one oncologist and one BMT physician).
Arm E: Neuroblastoma ** Neuroblastoma (ICD-O morphology 9500/3) or ganglioneuroblastoma (nodular or intermixed) verified by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites.
Disease Status at Enrollment
Arm A, Arm B and Arm D must have fit one of the following:
no evidence of disease or
stable, non-progressive disease (defined as non-progressive abnormalities on physical exam or CT and/or MRI) within 4 weeks of study entry
Arm C: Evidence of progressive or recurrent GCT (measurable or non-measurable) following one or more cisplatin-based chemotherapy, defined as meeting at least one of the following criteria:
Tumor biopsy of new or growing or unresectable lesions demonstrating viable non-teratomatous GCT. Patients with incomplete gross resection where viable GCT is found are considered eligible.
Consecutive elevated serum tumor markers (HCG or AFP) that are increasing. Increase of an elevated LDH alone does not constitute progressive disease.
Development of new or enlarging lesions in the setting of persistently elevated HCG or AFP, even if the HCG and AFP are not continuing to increase.
Arm E: Patients with the following disease stages at diagnosis are eligible, if they meet the other specified criteria.
Patients with newly diagnosed neuroblastoma with INSS Stage 4 are eligible with the following:
MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features or
Age > 18 months (> 547 days) regardless of biologic features or
Age 12-18 months (365-547 days) with any of the following 3 unfavorable biologic features (MYCN amplification, unfavorable pathology and/or DNA index = 1) or any biologic feature that is indeterminate/unsatisfactory/unknown.
Patients with newly diagnosed neuroblastoma with INSS Stage 3 are eligible with the following:
MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features or
Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status.
Patients with newly diagnosed neuroblastoma with INSS Stage 2A/2B with MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features.
Patients with newly diagnosed neuroblastoma with INSS Stage 4S with MYCN amplification (> 4-fold increase in MYCN expression signals as compared to reference signals), regardless of additional biologic features.
Patients ≥ 365 days initially diagnosed with neuroblastoma INSS Stage 1, 2, 4S who progressed to aStage 4 without interval chemotherapy.
Age and Performance Status
Age and Performance Status, Arm A
Age: 0 - 70 years
Performance status: Karnofsky Performance Status ≥ 50% for patients > 16 years of age or Lansky Play Score ≥ 50 for patients ≤ 16 years of age (Note: Neurologic deficits in patients with CNS tumors must be stable for a minimum of 1 week prior to study entry)
Age and Performance Status, Arm B
Age: see Eligible diseases, section 3.1, for age criteria
Performance status: Karnofsky Performance Status ≥ 50% for patients > 16 years of age or Lansky Play Score ≥ 50 for patients ≤ 16 years of age (Note: Neurologic deficits in patients with CNS tumors must be stable for a minimum of 1 week prior to study entry)
Age and Performance Status, Arm C
Age: 0-70 years of age
Performance status: Karnofsky Performance Status ≥ 70% for patients > 16 years of age or Lansky Play Score ≥ 70 for patients ≤ 16 years of age
Age and Performance Status, Arm D
Age: see Eligible diseases, section 3.1, for age criteria
Performance status: Karnofsky Performance Status ≥ 50% for patients > 16 years of age or Lansky Play Score ≥ 50 for patients ≤ 16 years of age (Neurologic deficits in patients with CNS tumors must be stable for a minimum of 1 week prior to study entry)
Age and Performance Status, Arm E
Age: Patients must be ≤ 30 years of age at the time of initial diagnosis.
Performance status: Karnofsky Performance Status ≥ 50% for patients > 16 years of age or Lansky Play Score ≥ 50 for patients ≤ 16 years of age
Organ Function
Organ Function, Arm A
Hematologic: hemoglobin of >9 gm/dl and platelet count > 20,000/μl. Patients may receive transfusions as necessary.
Renal: GFR ≥ 50 ml/min/1.73m2 or serum creatinine ≤ 2.5 x ULN for age
Hepatic: AST or ALT ≤ 5 x ULN and bilirubin ≤ 5 x ULN
Cardiac: ejection fraction ≥ 45% or no clinical evidence of heart failure
Pulmonary: oxygen saturation > 92% at rest (on room air)
Organ Function, Arm B (to begin first consolidation cycle)
Timing: patients must be fully recovered from radiation, induction chemotherapy or surgery prior to receiving consolidation, with minimum elapsed time of 2 weeks.
Hematologic: ANC > 750/μl, hemoglobin of >8 gm/dl (may receive PRBC transfusions) and platelet count > 75,000/μl (transfusion independent).
Renal: GFR ≥ 50 ml/min/1.73m2
Hepatic: AST or ALT ≤ 2.5 x ULN and bilirubin ≤ 1.5 x ULN
Cardiac: ejection fraction ≥ 45% or no clinical evidence of heart failure
Pulmonary: oxygen saturation > 94% at rest (on room air)
Central Nervous System: patients with seizure history are allowed if on anti-convulsants and well controlled; patients must not be in status epilepticus, coma or require assisted ventilation
Organ Function, Arm C (to begin TI chemotherapy)
Hematologic: ANC ≥ 750/mm3, platelets ≥ 75,000/mm3
Renal: GFR ≥ 50 ml/min/1.73m2 or serum creatinine ≤ 2.5 x ULN for age
Hepatic: AST or ALT ≤ 2.5 x upper limits of normal (ULN), if hepatic involvement < 5 x ULN; bilirubin ≤ 2.0 x upper limits of normal (ULN)
Arms A and C: Patients with a history of CNS tumor involvement are eligible if they have completed treatment for CNS disease (radiotherapy or surgery or chemotherapy), have recovered from or stabilization of the side effects associated with the therapy and have no evidence of progressive CNS disease at the time of enrollment
Organ Function, Arm D
Timing: patients must be fully recovered from radiation, induction chemotherapy or surgery prior to receiving consolidation, with minimum elapsed time of 2 weeks.
Hematologic: ANC > 750/μl, hemoglobin of >8 gm/dl (may receive PRBC transfusions) and platelet count > 75,000/μl (transfusion independent).
Renal: GFR ≥ 50 ml/min/1.73m2
Hepatic: AST or ALT ≤ 2.5 x ULN and bilirubin ≤ 1.5 x ULN
Cardiac: ejection fraction ≥ 45% or no clinical evidence of heart failure
Pulmonary: oxygen saturation > 92% at rest (on room air)
Central Nervous System: patients with seizure history are allowed if on anti-convulsants and well controlled; patients must not be in status epilepticus, coma or require assisted ventilation
Organ Function, Arm E
No evidence of disease progression: defined as increase in tumor size of >25% or new lesions.
Timing: Recovery from last induction course of chemotherapy.
Minimum frozen PBSC of 4 x 106 CD34 cells/kg as 2 aliquots; i.e. 2 x 106 CD34 cells/kg for each transplant are mandatory. A third aliquot of 2 x 106 CD34 cells/kg is strongly recommended for back-up.
Hepatic: AST < 3 x upper normal
Cardiac: Shortening fraction ≥ 27%, or ejection fraction ≥ 50%, no clinical congestive heart failure.
Renal: Creatinine clearance or GFR > 60 ml/min/1.73m2 (If a creatinine clearance is performed at end of induction and the result is < 100 ml/min/1.73m2, a GFR must be performed using a nuclear blood sampling method or iothalamate clearance method. Camera method is NOT allowed as measure of GFR prior to or during Consolidation therapy for patients with GFR or creatinine clearance of < 100 ml/min/1.73m2.)
Exclusion Criteria:
Arm A, B, C, and D:
Pregnant or breastfeeding
Active, uncontrolled infection and/or human immunodeficiency virus (HIV) positive constitute progressive disease.
Concomitant enrollment on clinical study (such as COG study) that does not allow co-enrollment on this standard of care protocol (Arm B only)
Arm E: Pregnant or breastfeeding
Active, uncontrolled infection and/or HIV positive
Known contraindication to PBSC collection. Examples of contraindications might be a weight or size less than that determined to be feasible at the collecting institution, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure.
Patients that are 12-18 months of age with INSS Stage 4 and all 3 favorable biologic features (ie, non- amplified MYCN, favorable pathology, and DNA index > 1). Clinics and Surgery Center (CSC)
Real-Time Feedback (RTFB) to Improve Colonoscopy
To test whether real-time feedback during the withdrawal phase of colonoscopy improves quality of colonoscopy and the adenoma detection rate.
Piet de Groen
18 years and over
STUDY00007271
Inclusion Criteria:
• Any endoscopist willing to parcipate and performing routine colonscopy
Exclusion Criteria:
• No exclusion criteria
Digestive & Liver Health
Clinics and Surgery Center (CSC)
MT2022-44 Analysis of Autoinflammation in Chronic Granulomatous Disease Patients Undergoing Hematopoietic Cell Transplantation or Gene Therapy (PIDTC 6908)
Christen Ebens
SITE00001764
Clinics and Surgery Center (CSC)
HM2021-31: A Phase 1b Open-Label Study to Evaluate the Safety and Anti-cancer Activity of Loncastuximab Tesirine in Combination with Other Anti-cancer Agents in Patients with Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (LOTIS-7)
This protocol aims to characterize the safety and tolerability of loncastuximab tesirine in combination with gemcitabine, lenalidomide, polatuzumab vedotin, or umbralisib, and to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) for any of the combinations in subjects with relapsed or refractory B-cell Non-Hodgkin Lymphoma. This project aims to address the resistance mechanisms to single agent therapies and enhance efficacy by engaging different targets, in synergistic or additive manner.
Marie Hu
18 years and over
STUDY00015805
Inclusion Criteria:
Male or female participant aged 18 years or older
Pathologic diagnosis of relapsed (disease that has recurred following a response) or refractory (disease that failed to respond to prior therapy) B-NHL (2016 World Health Organization classification) who have failed, or been intolerant to any approved therapy and had received at least two systemic treatment regimens in dose-escalation part; and at least one systemic treatment regimen in dose-expansion part
DLBCL (including transformed diseases, but for Arms E and F, including transformed FL only)
HGBCL
FL
MZL
MCL (for Arm C only)
BL (for Arm C only)
Life expectancy of at least 24 weeks according to Investigator's judgement
Need of systemic treatment for any of the listed indications as assessed by the investigator, including indolent B-NHLs (e.g. FL and MZL)
Measurable disease as defined by the 2014 Lugano Classification
Availability of formalin-fixed paraffin-embedded tumor tissue block
ECOG performance status 0 to 2
Adequate organ function
Women of childbearing potential (WOCBP) must agree to use a highly effective method of contraception from the time of giving informed consent until at least 10 months after the last dose of loncastuximab tesirine. Men with female partners who are of childbearing potential must agree to use a condom when sexually active or practice total abstinence from the time of giving informed consent the first dose until at least 7 months after the last dose of loncastuximab tesirine. Men must refrain from donating sperm during this same period. For the arm that includes glofitamab, WOCBP must agree to use contraceptive methods that result in a failure of <1% per year or remain abstinent (refrain from heterosexual intercourse) during the treatment period and for at least 18 months after pretreatment with obinutuzumab. For the arm that includes mosunetuzumab, WOCBP must agree to use contraceptive methods that result in a failure of <1% per year or remain abstinent (refrain from heterosexual intercourse) during the treatment period and for at least 3 months after the final dose of mosunetuzumab and tocilizumab (if applicable).
Exclusion Criteria:
Known history of hypersensitivity resulting in treatment discontinuation to or positive serum human ADA to a CD19 antibody
Previous therapy with loncastuximab tesirine
Previous treatment with polatuzumab vedotin, glofitamab or mosunetuzumab (applied to relevant arm and/or cohort of the specific drug administered)
Participants who received previous treatment of polatuzumab vedotin containing regimen will be excluded from Arm C
Participants who received previous treatment of glofitamab containing regimen will be excluded from Arm E
Participants who received previous treatment of mosunetuzumab containing regimen will be excluded from Arm F
Allogenic or autologous stem cell transplant within 60 days prior to start of study drug (C1 D1)
Human immunodeficiency virus (HIV) seropositive
Serologic evidence of chronic hepatitis B virus (HBV) infection and unable or unwilling to receive standard prophylactic antiviral therapy or with detectable HBV viral load
Serologic evidence of hepatitis C virus (HCV) infection without completion of curative treatment or with detectable HCV viral load
History of confirmed progressive multifocal leukoencephalopathy
History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or macrophage activation syndrome (MAS)/hemophagocytic lymphohistiocytosis (HLH)
Lymphoma with active central nervous system (CNS) involvement at the time of screening, including leptomeningeal disease
Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath)
Breastfeeding or pregnant
Significant medical comorbidities
Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy, within 14 days prior to start of study drugs (C1 D1), except shorter if approved by the Sponsor
Live vaccine within 4 weeks prior to C1D1
Failure to recover to Grade ≤1 (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) from acute non-hematologic toxicity (Grade ≤2 alopecia) due to previous therapy prior to screening
Active second primary malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the Sponsor's medical monitor and Investigator agree and document should not be exclusionary
Extra Exclusion Criteria for Arms E (includes glofitamab) and F (includes mosunetuzumab) Note: as applicable, the arm-specific exclusion criteria may supersede the general ones, such as stem cell transplant.
Prior allogeneic stem cell transplant and solid organ transplant
Autologous stem cell transplant within 100 days prior to C1D1
History of CNS lymphoma or leptomeningeal infiltration
Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
Known active infection, reactivation of a latent infection, whether bacterial, viral, fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within four weeks prior to C1D1
Active or history of autoimmune disease or immune deficiency, including but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain Barré syndrome, or multiple sclerosis, with certain exceptions
Prior treatment with anti-cancer/lymphoma targeted therapies (e.g., tyrosine kinase inhibitors, systemic immunotherapeutic/immunostimulating agents, including, but not limited to, cluster of differentiation 137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), anti-programmed cell death protein 1 (PD1), and anti-programmed death ligand 1 (PDL1) therapeutic antibodies, radio-immunoconjugates, ADCs, immune/cytokines and monoclonal antibodies) or treatment with systemic immunosuppressive medication (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to C1D1, or anticipation of need for systemic immunosuppressive medication during study treatment, with certain exceptions
Prior treatment with chimeric antigen receptor T-cell therapy within 30 days prior to C1D1
Toxicities from prior anti-cancer therapy including immunotherapy that did not resolve to ≤ Grade 1 with the exception of alopecia, endocrinopathy managed with replacement therapy and stable vitiligo
Any history of immune-related Grade ≥3 AE with the exception of endocrinopathy managed with replacement therapy
Ongoing corticosteroid use >25 mg/day of prednisone or equivalent within 4 weeks prior and during study treatment
Administration of a live attenuated vaccine within 4 weeks prior to the first dose of study treatment or anticipation that such a live attenuated vaccine will be required during the study or within 5 months after last dose of study treatment
Extra Exclusion Criteria for Arm E (includes glofitamab) only.
• Known history of hypersensitivity to obinutuzumab Clinics and Surgery Center (CSC)
MT2017-17: Alpha/Beta T Cell Depleted (alpha/beta TCD) Hematopoietic Cell Transplantation in Patients with Fanconi Anemia
The primary objective is to determine the incidence of grade II-IV acute graft versus host disease (GVHD) by Day 100 using an alpha/beta T cell depleted peripheral blood stem cells (PBSC) and without routine GVHD prophylaxis.
Margaret MacMillan, MD
STUDY00003182
Clinics and Surgery Center (CSC)