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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Myeloid Leukemia; Stem Cell Transplantation
• Intervention / Treatment: Drug: MT-401

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

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mythilli Koneru, MD, PhD; Phone Number: 713.400.6400; Email: mkoneru@markertherapeutics.com
• Study Contact Backup: Name: Gerald Garrett; Phone Number: 713.400.6400; Email: ggarrett@markertherapeutics.com

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • La Jolla, California, United States, 92093
      • Moores Cancer Center at University of Californa San Diego
    • Los Angeles, California, United States, 90095
      • UCLA Department of Medicine
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale Cancer Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinical Cancer Center-Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 303222
      • Winship Cancer Institute of Emory University
  • Illinois
    • Chicago, Illinois, United States, 77027
      • University of Chicago
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals & Clinics
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center-Rochester
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center At Hackensack UMC
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10027
      • Weill Cornell Medicine | NewYork-Presbyterian
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MT-401 following HSCT; Treatment with MT-401 at 90 days following HSCT	Drug: MT-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.; Other Names: zedenoleucel
No Intervention: Standard of Care following HSCT; Standard of Care
Experimental: MT-401 following relapse; Treatment with MT-401 following relapse after first HSCT	Drug: MT-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.; Other Names: zedenoleucel

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Marker Therapeutics, Inc.
• Investigators: Study Director: Mythili Koneru, MD, PhD, Marker Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2020
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: July 30, 2020
• First Submitted That Met QC Criteria: August 10, 2020
• First Posted (Actual): August 13, 2020

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: MRKR-19-401; FD-R-7272 (Other Grant/Funding Number: Office of Orphan Products Development)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No