Study of MGTA-117 in Patients With Adult Acute Myeloid Leukemia (AML) and Myelodysplasia-Excess Blasts (MDS-EB)

A Phase I/II, Dose-Escalation Study of MGTA-117 in Patients With Adult Acute Myeloid Leukemia (AML) and Myelodysplasia-Excess Blasts (MDS-EB)

This research study is designed to selectively deplete CD117-positive cells from participants with AML and MDS-EB.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia; Myelodysplasia
• Intervention / Treatment: Biological: MGTA-117

Detailed Description

This is a multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and potential anti-leukemia activity and to establish the minimum safe and biologically-effective dose of a single dose of MGTA-117 in relapsed/refractory (R/R) CD117+ AML participants and participants with MDS-EB. The study consists of escalating single-dose cohorts using a standard 3+3 design.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute at HealthONE
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Kansas
    • Westwood, Kansas, United States, 66205
      • The University of Kansas Cancer Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Buffalo, New York, United States, 14203
      • Roswell Park Comprehensive Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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

   OR

   - Presence of MRD in morphologic CR

2. CD117+ based on IHC or flow cytometry
3. Participant must have an identified HSC donor (related donor or unrelated donor), haplo-identical transplant donor, or umbilical blood donor.
4. Participant's Eastern Cooperative Oncology Group (ECOG) performance status must be ≤2.
5. 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.
6. Estimated creatinine clearance ≥60 mL/min
7. Adequate cardiac function as demonstrated by cardiac left ventricular ejection fraction ≥40% or perform New York Heart Association (NYHA) classification I and II

Exclusion Criteria:

1. Acute promyelocytic leukemia (APL).
2. Known active central nervous system (CNS) leukemia or chloroma (granulocyte sarcoma).
3. Received HSCT within 6 months prior to dosing
4. Received chimeric antigen-receptor cell therapies within 6 months prior to dosing
5. Has active graft-versus-host disease (GVHD).
6. Active hepatitis B (Hep-B) or hepatitis C (Hep-C) infection or history of human immunodeficiency virus (HIV).
7. Participant with a QTc value >470 msec
8. Participant has received another investigational drug or device within 14 days or 5 half-lives of dosing, whichever is longer.
9. Participant has any clinically significant medical condition, which in the opinion of the Investigator may place the participant at an unacceptable risk.
10. Active uncontrolled systemic bacterial, fungal, or viral infection
11. Participant has a history of serious allergic reactions, which in the opinion of the Investigator may pose an increased risk of serious infusion reactions.
12. Participant has had any systemic antileukemia treatment within 14 days except hydroxyurea, which is permitted until 24 hours prior to MGTA-117 dosing.
13. Participant has received prior anti-CD117 antibody treatment.
14. Participant has received gemtuzumab ozogamicin (Mylotarg) within the last 3 months prior to dosing.
15. Participant has received recent monoclonal antibody as anti-leukemic therapy within the last 30 days or 5 half-lives, whichever is longer.
16. Participant has received recent vaccination within the last 14 days prior to dosing.
17. Participant has Grade 2 or higher electrolyte abnormality at screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Single dose MGTA-117; Dosing of MGTA-117 prepared and administered by IV infusion.	Biological: MGTA-117; MGTA-117 will be administered as an IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence rate of treatment emergent adverse events (TEAEs) leading to study drug discontinuation		21 days
Incidence rate of treatment emergent >= Grade 3 clinical laboratory abnormalities as assessed by CTCAE v5.0		21 days
Assess the clinically significant changes from baseline in vital signs, ECGs and laboratory parameters		21 days
Pharmacokinetics profile of MGTA-117	Investigate area under the curve (AUC)	21 days
Pharmacokinetics profile of MGTA-117	Investigate maximum plasma concentration (Cmax)	21 days
Pharmacokinetics profile of MGTA-117	Investigate time of maximum concentration (Tmax)	21 days
Pharmacokinetics profile of MGTA-117	Investigate the half-life (t1/2)	21 days
Pharmacokinetics profile of MGTA-117	Investigate the plasma concentration	21 days
To establish a minimum safe and biologically effective dose	Assess the CD117 receptor occupancy in circulating leukemic blasts	7 days
To establish a minimum safe and biologically effective dose	The incidence of qualifying protocol-defined dose-limiting toxicities	21 days

Collaborators and Investigators

• Sponsor: Magenta Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 14, 2022
• Primary Completion (ACTUAL): February 2, 2023
• Study Completion (ACTUAL): February 2, 2023

Study Registration Dates

• First Submitted: January 14, 2022
• First Submitted That Met QC Criteria: February 3, 2022
• First Posted (ACTUAL): February 4, 2022

Study Record Updates

• Last Update Posted (ESTIMATE): February 9, 2023
• Last Update Submitted That Met QC Criteria: February 6, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; Hematopoietic stem cell transplant; Myelodysplasia-Excess Blasts; MGTA-117
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia
• Other Study ID Numbers: 117-HEM-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No