Efficacy of MT-401 in Patients With AML Following Stem Cell Transplant

Study Overview
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Brief Summary
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This study is a Phase 2 multicenter study with a Safety Lead-in evaluating safety and efficacy of MT-401 administration to patients with AML, who have received their first allogeneic HSCT. The dose administered is 50 x 10^6 cells (flat dosing).

Detailed Description
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This study is in patients aged ≥18 years old undergoing or having relapsed after their first allogeneic HSCT (matched sibling, matched unrelated donor, or haploidentical transplants) for AML. Potential patients for the study may be screened/enrolled: • Prior to their first allogeneic HSCT. or • Patients experiencing their first relapse post-allogeneic transplant. Patients eligible for the study will be placed into one of two groups: Adjuvant (Group 1): Patients screened prior to their HSCT with CR without minimal residual disease (CRMRD-) at 85-130 days post transplant will be randomized (1:1) in an unblinded fashion to: MT-401 (Arm A) SOC (Arm B) Active Disease: (Group 2): Patients meeting the following criteria will be assigned to Group 2 and will receive MT 401: Patients who experience relapse (patients with MRD [MRD+] or frank relapse) at or prior to post-transplant Day 85-130 Patients in Arm B of Group 1 (SOC) who develop relapse (MRD+ or frank relapse) post-HSCT (crossover patients) Patients who do not consent prior to HSCT but are experiencing their first relapse (MRD+ or frank relapse) and have the same donor available for manufacturing

Official Title
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A Phase 2 Study of Donor-Derived Multi-Tumor-Associated Antigen Specific T Cells (MT-401) Administered to Patients With Acute Myeloid Leukemia (AML) Following Hematopoietic Stem Cell Transplantation

Conditions
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Acute Myeloid Leukemia, Stem Cell Transplantation

Intervention / Treatment
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* Drug: MT-401


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria First allogeneic HSCT, in ≤ CR2, and MRD negative prior to transplant (including matched sibling, MUD with at least 6 of 8 HLA markers, or haploidentical with at least 5 of 10 HLA markers) as: Adjuvant therapy for AML (Group 1) at 85-130 days post-HSCT defined as patients with CRMRD; or Treatment for refractory/relapsed AML (first relapse post-HSCT) when disease occurs after transplant (Group 2) defined as First relapse (MRD+ or frank relapse) post-HSCT Patients in Arm 1B (SOC) who experience first relapse (MRD+ or frank relapse) post HSCT Safety Lead-in defined as patients who fit all the criteria for Group 2 only Are ≥18 years of age Karnofsky/Lansky score of ≥60 Life expectancy ≥12 weeks Adequate blood, liver, and renal function Blood: Hemoglobin ≥7.0 g/dL (can be transfused) Liver: Bilirubin ≤2X upper limit of normal; aspartate aminotransferase ≤3X upper limit of normal Renal: Serum creatinine ≤2X upper limit of normal or measured or calculated creatinine clearance ≥45mL/min 7. Patients are allowed to be on experimental conditioning regimens prior to transplant if no planned maintenance therapy post-transplant. 8. In Group 2, patients may receive bridging therapy at the investigators' discretion in situations where MT-401 is not ready for administration or the treating physician believes the patient would benefit Exclusion Criteria Clinically significant or severely symptomatic intercurrent infection Pregnant or lactating For Group 1, anti-neoplastic therapy after HSCT and prior to or during dosing of MT-401 For Group 2, concomitant anti-neoplastic therapy during or after dosing of MT-401 Evidence of acute or chronic GVHD ≥Grade 2 (exception: acute or chronic Grade 2 GVHD of skin allowed if stable) within one week prior to receiving MT-401

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MT-401 following HSCT<br>Treatment with MT-401 at 90 days following HSCT | Drug: MT-401<br>* MT-401 (zedenoleucel) is an allogeneic multi-tumor-associated antigen (MultiTAA)-specific T cell product manufactured under Good Manufacturing Practice (GMP) using donor-derived T cells obtained from apheresis.<br>* Other names: zedenoleucel;|
| No Intervention: Standard of Care following HSCT<br>Standard of Care | |
| Experimental: MT-401 following relapse<br>Treatment with MT-401 following relapse after first HSCT | Drug: MT-401<br>* MT-401 (zedenoleucel) is an allogeneic multi-tumor-associated antigen (MultiTAA)-specific T cell product manufactured under Good Manufacturing Practice (GMP) using donor-derived T cells obtained from apheresis.<br>* Other names: zedenoleucel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Lead-In | Number of participants with MT-401 Dose Limiting Toxicities (DLTs) | Baseline through Cycle 1 (28 Days) | 
| Phase 2 Adjuvant Group | Relapse Free Survival (RFS), defined as the time from randomization to first disease recurrence or death from any cause. | Up to 24 months after the first participant is randomized | 
| Phase 2 Active Disease Group | Complete Remission (CR), per European LeukemiaNet (ELN) 2017 criteria | Up to 12 months | 
| Phase 2 Active Disease Group | Duration of CR (DOCR), defined as the time from the first observation of CR through disease recurrence or death from any cause | Up to 24 months |