Clinical Trial 21763

• Overview

  Study Title:

  MRKR-21-401-OTS - A Phase 1 Study of Allogeneic Off-the-Shelf Multi-Tumor-Associated Antigen-Specific T Cells (MT-401-OTS) Administered to Patients with Relapsed Acute Myeloid Leukemia or Myelodysplastic Syndromes (RAPID)

  Objective:

  Primary: To assess the safety and tolerability of MT-401-OTS Secondary: To assess the efficacy of MT-401-OTS in participants with high risk or very-high-risk MDS per IPSS-M who have evidence of disease following at least 4 cycles of an HMA To assess the efficacy of MT-401-OTS in participants with intermediate or high-risk AML per 2002 ELN criteria who have evidence of disease following induction therapy or at least 4 cycles of nonintensive treatment Exploratory: To evaluate additional measures of efficacy To examine the expansion, persistence, clonality, and anti-tumor immune effects of MT-401-OTS in all dose cohorts

• Treatments

  Therapies:

  Cell Therapy; Chemotherapy (NOS)

  Medications:

  Azacitidine (5-azacitidine); Bendamustine (); MESNA (); MT-401-OTS (); cyclophosphamide (); cytoxan (cyclophosphamide); decitabine (5-aza-2'-deoxycytidine); fludarabine (Fludarabine phosphate)

• Inclusion Criteria

  Key Inclusion Criteria:
  • Must be ≥ 65 years of age and capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in the protocol, at the time of signing the ICF
  • Must have a life expectancy ≥ 12 weeks
  • Must have an ECOG performance status of 0-2
  • Must have available MT-401-OTS product with a ≥ 2/8 HLA match Disease Characteristics
  • For participants with AML: Must have a confirmed diagnosis of AML or MDS/AML per 2022 WHO Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms or 2022 International Consensus Criteria. Must have intermediate or high-risk disease based on ELN 2022 criteria. If no targetable mutation is present, must have received 1 prior standard regimen with at least 4 cycles of standard therapy containing an HMA or a standard cytarabine-containing induction therapy If targetable mutation is present, must have received a regimen that includes commercially available targeted therapy unless unable to tolerate or the participant declines (must be documented in the informed consent). If targeted therapy was not administered as part of first-line of therapy, a second regimen is allowed. Must have either: ≤ 10% bone marrow blasts and ≤ 5% peripheral blasts during screening and not be considered to have hyperproliferating disease at diagnosis or after treatment OR Evidence of MRD based on evaluation at a local laboratory.
  • For participants with MDS: Must have confirmed diagnosis of MDS based on 2022 WHO Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms or 2022 ICC criteria. Must have high-risk or very-high-risk disease based on IPSS-M (ie, not evolved to AML) Must have received standard treatment with at least 4 cycles of an HMA and have evidence of continued disease, including morphologic disease or MRD-positive Must have bone marrow blasts ≤ 10% at screening Health Status
  • Must have adequate coagulation, hepatic, renal, and cardiac function.
  • Additional criteria may apply.

• Exclusion Criteria

  Key Exclusion Criteria:
  • Have leukemic involvement in the CNS.
  • Have other extramedullary disease involvement (except hepatosplenic involvement).
  • Have APL Medical Conditions.
  • Have primary immunodeficiency.
  • Have severe or uncontrolled autoimmune disorder.
  • Have a history or presence of clinically relevant CNS pathology, such as epilepsy, seizure, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome or psychosis.
  • Have active malignancies (ie, those that are progressing or have required treatment change in the last 24 months) other than the disease being treated under study.
  • Have any active systemic infection requiring therapy (viral, bacterial, or fungal), including HIV.
  • Have active hepatitis B or C infection or other clinically active liver diseases.
  • Have Class III or IV congestive heart failure per New York Association.
  • Have unstable angina.
  • Have a history or evidence of current, uncontrolled, clinically significant, unstable arrhythmias.
  • Have an oxygen saturation on room air of ≤ 92%.
  • Have clinically significant reversible nonhematologic toxicities from prior cancer therapy that have not recovered to Grade 1 or baseline Note: Participants with clinically nonsignificant toxicities, such as asymptomatic laboratory values, will be allowed on study.
  • Received prior treatments for underlying malignancy, except as specified in the Inclusion Criteria. Participants with AML secondary to MDS may have received prior treatment for MDS.
  • Have had prior HSCT.
  • Are receiving concurrent therapies other than HMA, as delineated in the study design.
  • Have received hematopoietic growth factors within 2 days of lymphodepleting conditioning regimen.
  • Have a history of severe allergic reactions/intolerance to any of the study intervention components, including the conditioning regimen, HMA, or DSMO, or to tocilizumab.
  • Have had major surgery within 14 days (central line placement allowed).
  • Have received systemic steroids (exception: physiological doses of steroids allowed) or other immunosuppressive therapies within 14 days prior to lymphodepleting conditioning regimen.
  • Are unable to be matched with MT-401-OTS product inventory.
  • Are pregnant or breastfeeding.
  • Have any other issue that, in the opinion of the treating physician, would make the participant ineligible for the study or unable to comply with its requirements.
  • Additional criteria may apply.

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