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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04113616
Recruitment Status : Recruiting
First Posted : October 3, 2019
Last Update Posted : May 13, 2020
Sponsor:
Information provided by (Responsible Party):
Kartos Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE October 1, 2019
First Posted Date  ICMJE October 3, 2019
Last Update Posted Date May 13, 2020
Actual Study Start Date  ICMJE September 25, 2019
Estimated Primary Completion Date December 15, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 22, 2019)
  • Part A: Number of dose-limiting toxicities (DLTs) of KRT-232 in combination with cytarabine or decitabine [ Time Frame: 28 Days ]
  • Part B: Proportion of patients achieving complete remission (CR) or complete remission with partial hematological improvement (CRh) as determined by European LeukemiaNet (ELN) response criteria [ Time Frame: 28 Days ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 1, 2019)
  • Part A: To determine the KRT-232 recommended phase 2 dose (RP2D) in combination with Cytarabine or Decitabine. [ Time Frame: 28 Days ]
    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.
  • Part B: To determine the rates of complete remission (CR) and complete remission with partial hematological improvement (CRh) [ Time Frame: 28 Days ]
    The proportion of patients achieving a CR or PR as determined by Eurpean LeukemiaNet (ELN) response criteria after at least 1 cycle of treatment of the recommended dose (RP2D) from Part A.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 22, 2019)
  • Part A: Proportion of patients achieving complete remission (CR) or complete remission with partial hematological improvement (CRh) as determined by European LeukemiaNet (ELN) response criteria [ Time Frame: 28 Days ]
  • 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) [ Time Frame: 28 Days ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 1, 2019)
  • Part A: To determine the rates of complete remission (CR) and complete remission with partial hematological improvement (CRh) [ Time Frame: 28 Days ]
    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.
  • To determine the overall response rate (ORR) [ Time Frame: 28 Days ]
    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).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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)
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukemia (AML)
  • Acute Myeloid Leukemia (AML), Secondary to Myeloproliferative Neoplasms (MPN)
Intervention  ICMJE
  • Drug: KRT-232
    KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth.
  • Drug: Cytarabine
    Cytarabine is an anti-cancer chemotherapy drug taken via injection.
    Other Names:
    • cytosine arabinoside
    • Cytosar-U
    • Depocyt
    • Arabinosylcytosine
    • Ara-C
  • Drug: Decitabine
    Decitabine is an anti-cancer chemotherapy drug taken via injection.
    Other Name: Dacogen
Study Arms  ICMJE
  • Experimental: KRT-232+LDAC
    KRT-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.
    Interventions:
    • Drug: KRT-232
    • Drug: Cytarabine
  • Experimental: KRT-232(7-Day)+Decitabine
    KRT-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.
    Interventions:
    • Drug: KRT-232
    • Drug: Decitabine
  • Experimental: KRT-232(14-Day)+Decitabine
    KRT-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.
    Interventions:
    • Drug: KRT-232
    • Drug: Decitabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 1, 2019)
160
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 15, 2024
Estimated Primary Completion Date December 15, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Yulia Khalina 908-656-2799 ykhalina@kartosthera.com
Contact: John Mei 650-542-0136 jmei@kartosthera.com
Listed Location Countries  ICMJE Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04113616
Other Study ID Numbers  ICMJE KRT-232-104
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Kartos Therapeutics, Inc.
Study Sponsor  ICMJE Kartos Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Kartos Therapeutics, Inc.
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP