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

Sponsor

Magenta Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05223699

Collaborator

(none)

Enrollment

Locations

Arm

19.5

Anticipated Duration (Months)

9.2

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Myelodysplasia	Biological: MGTA-117	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

55 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 14, 2022

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Oct 1, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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 [21 days]
Investigate area under the curve (AUC)
Pharmacokinetics profile of MGTA-117 [21 days]
Investigate maximum plasma concentration (Cmax)
Pharmacokinetics profile of MGTA-117 [21 days]
Investigate time of maximum concentration (Tmax)
Pharmacokinetics profile of MGTA-117 [21 days]
Investigate the half-life (t1/2)
Pharmacokinetics profile of MGTA-117 [21 days]
Investigate the plasma concentration
To establish a minimum safe and biologically effective dose [7 days]
Assess the CD117 receptor occupancy in circulating leukemic blasts
To establish a minimum safe and biologically effective dose [21 days]
The incidence of qualifying protocol-defined dose-limiting toxicities

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

The participant has a WHO-defined diagnosis of MDS-EB and has failed/is refractory to HMA

Presence of MRD in morphologic CR

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

Exclusion Criteria:

Acute promyelocytic leukemia (APL).
Known active central nervous system (CNS) leukemia or chloroma (granulocyte sarcoma).
Received HSCT within 6 months prior to dosing
Received chimeric antigen-receptor cell therapies 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	Moffitt Cancer Center	Tampa	Florida	United States	33612
3	The University of Kansas Cancer Center	Westwood	Kansas	United States	66205
4	University of Minnesota	Minneapolis	Minnesota	United States	55455
5	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
6	MD Anderson Cancer Center	Houston	Texas	United States	77030