Clinical trial NCT04511130: Efficacy of MT-401 in Patients With AML Following Stem Cell Transplant
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Stem Cell Transplantation
Lead sponsor: Marker Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2020-08-13
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Safety Lead-In
timeFrame: Baseline through Cycle 1 (28 Days)
measure: Phase 2 Adjuvant Group
timeFrame: Up to 24 months after the first participant is randomized
measure: Phase 2 Active Disease Group
timeFrame: Up to 12 months
measure: Phase 2 Active Disease Group
timeFrame: Up to 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: La Jolla
country: United States
facility: Moores Cancer Center at University of Californa San Diego
state: California
city: Los Angeles
country: United States
facility: UCLA Department of Medicine
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinical Cancer Center-Florida
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center-Rochester
state: Minnesota
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack UMC
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine | NewYork-Presbyterian
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Marker Therapeutics
name: Mythili Koneru, MD, PhD
role: STUDY_DIRECTOR
References: