Study of MGTA-117 in Patients With Adult Acute Myeloid Leukemia (AML) and Myelodysplasia-Excess Blasts (MDS-EB)
Primary Purpose
Acute Myeloid Leukemia, Myelodysplasia
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
MGTA-117
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Acute Myeloid Leukemia, Myelodysplasia-Excess Blasts, MGTA-117, Hematopoietic stem cell transplant
Eligibility Criteria
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
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
- 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
Sites / Locations
- City of Hope
- Sarah Cannon Research Institute at HealthONE
- Moffitt Cancer Center
- The University of Kansas Cancer Center
- University of Minnesota
- Washington University School of Medicine
- Roswell Park Comprehensive Cancer Center
- MD Anderson Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single dose MGTA-117
Arm Description
Dosing of MGTA-117 prepared and administered by IV infusion.
Outcomes
Primary Outcome Measures
Incidence rate of treatment emergent adverse events (TEAEs) leading to study drug discontinuation
Incidence rate of treatment emergent >= Grade 3 clinical laboratory abnormalities as assessed by CTCAE v5.0
Assess the clinically significant changes from baseline in vital signs, ECGs and laboratory parameters
Pharmacokinetics profile of MGTA-117
Investigate area under the curve (AUC)
Pharmacokinetics profile of MGTA-117
Investigate maximum plasma concentration (Cmax)
Pharmacokinetics profile of MGTA-117
Investigate time of maximum concentration (Tmax)
Pharmacokinetics profile of MGTA-117
Investigate the half-life (t1/2)
Pharmacokinetics profile of MGTA-117
Investigate the plasma concentration
To establish a minimum safe and biologically effective dose
Assess the CD117 receptor occupancy in circulating leukemic blasts
To establish a minimum safe and biologically effective dose
The incidence of qualifying protocol-defined dose-limiting toxicities
Secondary Outcome Measures
Full Information
NCT ID
NCT05223699
First Posted
January 14, 2022
Last Updated
February 6, 2023
Sponsor
Magenta Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05223699
Brief Title
Study of MGTA-117 in Patients With Adult Acute Myeloid Leukemia (AML) and Myelodysplasia-Excess Blasts (MDS-EB)
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)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Terminated
Why Stopped
Sponsor Decision
Study Start Date
February 14, 2022 (Actual)
Primary Completion Date
February 2, 2023 (Actual)
Study Completion Date
February 2, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Magenta Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Myelodysplasia
Keywords
Acute Myeloid Leukemia, Myelodysplasia-Excess Blasts, MGTA-117, Hematopoietic stem cell transplant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single dose MGTA-117
Arm Type
Experimental
Arm Description
Dosing of MGTA-117 prepared and administered by IV infusion.
Intervention Type
Biological
Intervention Name(s)
MGTA-117
Intervention Description
MGTA-117 will be administered as an IV infusion
Primary Outcome Measure Information:
Title
Incidence rate of treatment emergent adverse events (TEAEs) leading to study drug discontinuation
Time Frame
21 days
Title
Incidence rate of treatment emergent >= Grade 3 clinical laboratory abnormalities as assessed by CTCAE v5.0
Time Frame
21 days
Title
Assess the clinically significant changes from baseline in vital signs, ECGs and laboratory parameters
Time Frame
21 days
Title
Pharmacokinetics profile of MGTA-117
Description
Investigate area under the curve (AUC)
Time Frame
21 days
Title
Pharmacokinetics profile of MGTA-117
Description
Investigate maximum plasma concentration (Cmax)
Time Frame
21 days
Title
Pharmacokinetics profile of MGTA-117
Description
Investigate time of maximum concentration (Tmax)
Time Frame
21 days
Title
Pharmacokinetics profile of MGTA-117
Description
Investigate the half-life (t1/2)
Time Frame
21 days
Title
Pharmacokinetics profile of MGTA-117
Description
Investigate the plasma concentration
Time Frame
21 days
Title
To establish a minimum safe and biologically effective dose
Description
Assess the CD117 receptor occupancy in circulating leukemic blasts
Time Frame
7 days
Title
To establish a minimum safe and biologically effective dose
Description
The incidence of qualifying protocol-defined dose-limiting toxicities
Time Frame
21 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
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
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
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Sarah Cannon Research Institute at HealthONE
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
The University of Kansas Cancer Center
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Roswell Park Comprehensive Cancer Center
City
Buffalo
State/Province
New York
ZIP/Postal Code
14203
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study of MGTA-117 in Patients With Adult Acute Myeloid Leukemia (AML) and Myelodysplasia-Excess Blasts (MDS-EB)
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