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

Phase 1

Terminated

• Conditions: Myelodysplasia; Acute Myeloid Leukemia
• Interventions: Biological: MGTA-117

• Registration Number: NCT05223699
• Lead Sponsor: Magenta Therapeutics, Inc.

Brief Summary

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

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 Timeline

• Study First Submitted: 2022-01-14
• Study First Submitted QC: 2022-02-03
• Study First Posted: 2022-02-04
• Study Start: 2022-02-14
• Status Verified: 2023-02
• Primary Completion: 2023-02-02
• Study Completion: 2023-02-02
• Last Update Submitted: 2023-02-06
• Last Update Posted: 2023-02-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 22

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Single dose MGTA-117	MGTA-117	Dosing of MGTA-117 prepared and administered by IV infusion.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics profile of MGTA-117	21 days	Investigate the plasma concentration
Incidence rate of treatment emergent adverse events (TEAEs) leading to study drug discontinuation	21 days
To establish a minimum safe and biologically effective dose	21 days	The incidence of qualifying protocol-defined dose-limiting toxicities
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

Trial Locations

Locations (8)

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

Sarah Cannon Research Institute at HealthONE; 🇺🇸 Denver, Colorado, United States

Roswell Park Comprehensive Cancer Center; 🇺🇸 Buffalo, New York, United States

City of Hope; 🇺🇸 Duarte, California, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

The University of Kansas Cancer Center; 🇺🇸 Westwood, Kansas, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States