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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)

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ClinicalTrials.gov Identifier: NCT04113616
Recruitment Status : Recruiting
First Posted : October 3, 2019
Last Update Posted : November 26, 2019
Sponsor:
Information provided by (Responsible Party):
Kartos Therapeutics, Inc.

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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia (AML) Acute Myeloid Leukemia (AML), Secondary to Myeloproliferative Neoplasms (MPN) Drug: KRT-232 Drug: Cytarabine Drug: Decitabine Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : September 25, 2019
Estimated Primary Completion Date : December 15, 2023
Estimated Study Completion Date : July 15, 2024


Arm Intervention/treatment
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.
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

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.
Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth.

Drug: Decitabine
Decitabine is an anti-cancer chemotherapy drug taken via injection.
Other Name: Dacogen

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.
Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth.

Drug: Decitabine
Decitabine is an anti-cancer chemotherapy drug taken via injection.
Other Name: Dacogen




Primary Outcome Measures :
  1. Part A: Number of dose-limiting toxicities (DLTs) of KRT-232 in combination with cytarabine or decitabine [ Time Frame: 28 Days ]
  2. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04113616


Contacts
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Contact: Josh Martino 858-692-4700 jmartino@kartosthera.com
Contact: John Mei 650-542-0136 jmei@kartosthera.com

Locations
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United States, Ohio
The Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Kartos Therapeutics, Inc.

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Responsible Party: Kartos Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04113616     History of Changes
Other Study ID Numbers: KRT-232-104
First Posted: October 3, 2019    Key Record Dates
Last Update Posted: November 26, 2019
Last Verified: November 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myeloproliferative Disorders
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Cytarabine
Decitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors