We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 When Administered Alone and in Combination 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 : August 4, 2022
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 August 4, 2022
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: August 27, 2021)
  • Part A: To determine KRT-232 recommended phase 2 dose (RP2D) [ Time Frame: 28 Days ]
    Number of dose-limiting toxicities (DLTs) of KRT-232 in combination with cytarabine or decitabine
  • Part B: To determine the RP2D of KRT-232 [ Time Frame: 2 years after last patient enrolled ]
    The safety review committee (SRC) will determine the RP2D based on safety and tolerability data obtained from each arm
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: August 27, 2021)
  • Part A: To determine the rates of complete remission (CR) and complete remission with partial hematological improvement (CRh) [ Time Frame: 12 weeks ]
    Proportion of patients achieving complete remission (CR) or complete remission with partial hematological improvement (CRh) as determined by Modified 2017 European LeukemiaNet (ELN) response criteria
  • Part B: To determine the rates of complete remission (CR), CR with partial hematological improvement (CRh) and CR with incomplete hematologic recovery (CRi) [ Time Frame: 12 weeks ]
    Proportion of patients achieving complete remission (CR), complete remission with partial hematological improvement (CRh), and CR with incomplete hematologic recovery (CRi) as determined by Modified 2017 European LeukemiaNet (ELN) response criteria
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 When Administered Alone and in Combination 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 When Administered Alone and in Combination 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, when administered alone and in combination 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 monotherapy (KRT-232 alone) or combination therapy (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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Relapsed or Refractory 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: Part A - Arm 1

    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: Part A - Arm 2

    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: Part A - Arm 3

    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
  • Experimental: Part B - Arm 1
    KRT-232 administered at 360 mg orally, once daily (QD) on Days 1-7 with 21 days off on a 28-day treatment cycle
    Intervention: Drug: KRT-232
  • Experimental: Part B - Arm 2
    KRT-232 administered at 360 mg orally, once daily (QD) on Days 1-7 with 21 days off on a 28-day treatment cycle in Cycle 1, followed by 240 mg orally, once daily (QD) on Days 1-7 with 21 days off on a 28-day cycle, in the subsequent cycles.
    Intervention: Drug: KRT-232
  • Experimental: Part B - Arm 3
    KRT-232 administered at 180 mg orally, once daily (QD) on Days 1-7 with 14 days off on a 21-day treatment cycle.
    Intervention: Drug: KRT-232
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: August 27, 2021)		 86
Original Estimated Enrollment  ICMJE
 (submitted: October 1, 2019)		 160
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 relapsed or refractory AML secondary to MPN (myelofibrosis [MF], polycythemia vera [PV], or essential thrombocythemia [ET]); patients may have been treated with ≥1 prior lines of therapy for their AML secondary to MPN.
  • 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 (for Part A) .
  • Patients previously treated with decitabine are not eligible to receive decitabine on this study but may be treated with cytarabine (for Part A) .
  • Patients who have received an allogeneic HSCT within 90 days of enrollment or who have active graft-versus-host disease requiring active therapy (for Part A)
  • Allogeneic stem cell transplant within 3 months; autologous stem cell transplant within 3 months or active graft-versus-host disease prior to first dose of study treatment (for Part B)
  • Patients who have received immunosuppressive therapy for graft-versus-host disease within 1 month prior to enrollment into this study
  • Patients who are eligible for an allogeneic HSCT per the opinion of the investigator and have a donor. Patients who are HSCT-eligible in the opinion of the investigator, but who refuse a transplant, are eligible for the study.
  • 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 to the first treatment with KRT-232
  • 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: John Mei 650-542-0136 jmei@kartosthera.com
Contact: Timothy Sbardellati tsbardellati@kartosthera.com
Listed Location Countries  ICMJE Australia,   Belgium,   France,   Germany,   Hungary,   Israel,   Italy,   Korea, Republic of,   Poland,   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
Current Responsible Party Kartos Therapeutics, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Kartos Therapeutics, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Kartos Therapeutics, Inc.
Verification Date August 2022

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