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An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 Combined With Low-Dose Cytarabine (LDAC) or Decitabine in Patients With Acute Myeloid Leukemia (AML)

NCT04113616

Description:

This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, combined with low-dose cytarabine (LDAC) or Decitabine for the treatment of adults with Acute Myeloid Leukemia (AML) and AML secondary to myeloproliferative neoplasms (MPN). Participants must be relapsed/refractory (having failed prior therapy) and will be assigned to receive KRT+232 with LDAC or KRT-232 with Decitabine.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 Combined With Low-Dose Cytarabine (LDAC) or Decitabine in Patients With Acute Myeloid Leukemia (AML)
  • Official Title: An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 Combined With Low-Dose Cytarabine (LDAC) or Decitabine in Patients With Acute Myeloid Leukemia (AML)

Clinical Trial IDs

  • ORG STUDY ID: KRT-232-104
  • NCT ID: NCT04113616

Conditions

  • Acute Myeloid Leukemia (AML)
  • Acute Myeloid Leukemia (AML), Secondary to Myeloproliferative Neoplasms (MPN)

Interventions

DrugSynonymsArms
KRT-232KRT-232+LDAC
Cytarabinecytosine arabinoside, Cytosar-U, Depocyt, Arabinosylcytosine, Ara-CKRT-232+LDAC
DecitabineDacogenKRT-232(7-Day)+Decitabine

Purpose

This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, combined with low-dose cytarabine (LDAC) or Decitabine for the treatment of adults with Acute Myeloid Leukemia (AML) and AML secondary to myeloproliferative neoplasms (MPN). Participants must be relapsed/refractory (having failed prior therapy) and will be assigned to receive KRT+232 with LDAC or KRT-232 with Decitabine.

Trial Arms

NameTypeDescriptionInterventions
KRT-232+LDACExperimentalKRT-232 will be administered orally, once daily (QD), on Days 1-7 in combination with LDAC administered at 20 mg/m2/day subcutaneously on Days 1-10 in a 28-day cycle.
  • KRT-232
  • Cytarabine
KRT-232(7-Day)+DecitabineExperimentalKRT-232 will be administered orally, once daily (QD), on Days 1-7 in combination with Decitabine administered at 20 mg/m2/day intravenously on Days 1-5 in a 28-day cycle.
  • KRT-232
  • Decitabine
KRT-232(14-Day)+DecitabineExperimentalKRT-232 will be administered orally, once daily (QD), on Days 1-7 and Days 15-21 (7 days on/7 days off/7 days on/7 days off) in combination with Decitabine administered at 20 mg/m2/day intravenously on Days 1-5 in a 28-day cycle.
  • KRT-232
  • Decitabine

Eligibility Criteria

        Key Inclusion Criteria:

          -  Part A: Patients with relapsed or refractory AML, or newly-diagnosed AML secondary to
             MPN

          -  Part B: Patients with AML secondary to MPN or JAK2 mutation positive AML; patients may
             have been treated with 0 to 2 prior lines of therapy for their AML

          -  Adequate hepatic and renal function

          -  Appropriate prior treatment with an FLT3 or IDH1/2 inhibitor where applicable

        Key Exclusion Criteria:

          -  Patients who are TP53 mutation positive

          -  Prior treatment with an MDM2 antagonist therapy

          -  Patients treated with ≥ 18 g/m2 of cytarabine within the prior 90 days are not
             eligible to be treated with cytarabine on this study (but may be treated with
             decitabine)

          -  Patients previously treated with decitabine are not eligible to receive decitabine on
             this study (but may be treated with cytarabine)

          -  Patients who have received an allogeneic HSCT within 90 days of enrollment or are
             eligible for an allogeneic HSCT and have a donor (unless transplant is refused)

          -  Active graft-versus-host disease requiring active therapy or who have received
             immunosuppressive therapy for graft-versus-host disease within 1 month prior

          -  Patients with known CNS involvement with AML, acute promyelocytic leukemia (APL), or a
             history of bleeding diathesis

          -  Patients who have had major surgery within 28 days prior

          -  Women who are pregnant or breastfeeding
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part A: To determine the KRT-232 recommended phase 2 dose (RP2D) in combination with Cytarabine or Decitabine.
Time Frame:28 Days
Safety Issue:
Description:To assess dose-limiting toxicities (DLTs) of KRT-232 in combination with cytarabine and DLTs of KRT-232 in combination with decitabine at multiple dose levels.

Secondary Outcome Measures

Measure:Part A: To determine the rates of complete remission (CR) and complete remission with partial hematological improvement (CRh)
Time Frame:28 Days
Safety Issue:
Description:The proportion of patients achieving a CR or PR as determined by Eurpean LeukemiaNet (ELN) response criteria after at least 1 cycle of treatment at each dose level.
Measure:To determine the overall response rate (ORR)
Time Frame:28 Days
Safety Issue:
Description:The proportion of patients achieving a morphologic leukemia-free state (MLFS), or complete remission with incomplete hematology recovery (CRi), or composite complete remission (CRc = CR + CRh), or partial remission (PR).

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Kartos Therapeutics, Inc.

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