Acute Myeloid Leukemia, Stem Cell Transplantation
Conditions
Brief summary
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
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
Interventions
DRUGMT-401
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.
Sponsors
Marker Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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 2. Are ≥18 years of age 3. Karnofsky/ Lansky score of ≥60 4. Life expectancy ≥12 weeks 5. 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
1. Clinically significant or severely symptomatic intercurrent infection 2. Pregnant or lactating 3. For Group 1, anti-neoplastic therapy after HSCT and prior to or during dosing of MT-401 4. For Group 2, concomitant anti-neoplastic therapy during or after dosing of MT-401 5. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Lead-In | Baseline through Cycle 1 (28 Days) | Number of participants with MT-401 Dose Limiting Toxicities (DLTs) |
| Phase 2 Adjuvant Group | Up to 24 months after the first participant is randomized | Relapse Free Survival (RFS), defined as the time from randomization to first disease recurrence or death from any cause. |
| Phase 2 Active Disease Group | Up to 12 months | Complete Remission (CR), per European LeukemiaNet (ELN) 2017 criteria |
Countries
United States
Outcome results
None listed