MT2021-14 A PHASE I/II, DOSE-ESCALATION STUDY OF MGTA-117 IN PATIENTS WITH ADULT ACUTE MYELOID LEUKEMIA (AML) AND MYELODYSPLASIA-EXCESS BLASTS (MDS-EB)
The overall objective of this study is to investigate the safety, tolerability, PK, PD, and potential anti-leukemia activity of MGTA-117 given intravenously (IV) as a single dose in adults with R/R AML or MDS-EB. Once adequate data are available, the protocol will be amended to assess the safety/tolerability and preliminary efficacy of MGTA-117 in combination with reduced intensity conditioning (RIC) in patients with AML who are proceeding to HSCT.
• Participant must have a World Health Organization (WHO)-defined diagnosis of R/R AML and meet one of the following criteria:
• The participant has experienced primary AML induction failure or R/R AML OR The participant has a WHO-defined diagnosis of MDS-EB and has failed/is refractory to HMA
• CD117+ based on IHC or flow cytometry
• Participant must have an identified HSC donor (related donor or unrelated donor), haplo-identical transplant donor, or umbilical blood donor.
• Participant's Eastern Cooperative Oncology Group (ECOG) performance status must be ≤2.
• Participant must have adequate baseline hepatic function. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤2 x upper limit of normal (ULN), and serum bilirubin ≤1.5 x ULN.
• Estimated creatinine clearance ≥60 mL/min
• Adequate cardiac function as demonstrated by cardiac left ventricular ejection fraction ≥40% or perform New York Heart Association (NYHA) classification I and II
• Acute promyelocytic leukemia (APL).
• Known active central nervous system (CNS) leukemia or chloroma (granulocyte sarcoma).
• Received HSCT within 6 months prior to dosing
• Has active graft-versus-host disease (GVHD).
• Active hepatitis B (Hep-B) or hepatitis C (Hep-C) infection or history of human immunodeficiency virus (HIV).
• Participant with a QTc value >470 msec
• Participant has received another investigational drug or device within 14 days or 5 half-lives of dosing, whichever is longer.
• Participant has any clinically significant medical condition, which in the opinion of the Investigator may place the participant at an unacceptable risk.
• Active uncontrolled systemic bacterial, fungal, or viral infection
• Participant has a history of serious allergic reactions, which in the opinion of the Investigator may pose an increased risk of serious infusion reactions.
• Participant has had any systemic antileukemia treatment within 14 days except hydroxyurea, which is permitted until 24 hours prior to MGTA-117 dosing.
• Participant has received prior anti-CD117 antibody treatment.
• Participant has received gemtuzumab ozogamicin (Mylotarg) within the last 3 months prior to dosing.
• Participant has received recent monoclonal antibody as anti-leukemic therapy within the last 30 days or 5 half-lives, whichever is longer.
• Participant has received recent vaccination within the last 14 days prior to dosing.
• Participant has Grade 2 or higher electrolyte abnormality at screening
Acute Myeloid Leukemia, Myelodysplasia
Acute Myeloid Leukemia, Myelodysplasia-Excess Blasts, MGTA-117, Hematopoietic stem cell transplant, Clinics and Surgery Center (CSC)