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

Acute Myeloid Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05223699
• Other study ID #: 117-HEM-101
• Status: Terminated
• Phase: Phase 1
• Start date: February 14, 2022
• Est. completion date: February 2, 2023

Study information

• Verified date: February 2023
• Source: Magenta Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 22
• Est. completion date: February 2, 2023
• Est. primary completion date: February 2, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplasia
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Biological:
• MGTA-117
MGTA-117 will be administered as an IV infusion

Locations

Country	Name	City	State
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	Sarah Cannon Research Institute at HealthONE	Denver	Colorado
United States	City of Hope	Duarte	California
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Minnesota	Minneapolis	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Moffitt Cancer Center	Tampa	Florida
United States	The University of Kansas Cancer Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Magenta Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

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