Trial record 1 of 1 for:
KRT-232-104 | AML | Leipzig, Germany
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)
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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 |
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Recruitment Status :
Recruiting
First Posted : October 3, 2019
Last Update Posted : August 4, 2022
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Sponsor:
Kartos Therapeutics, Inc.
Information provided by (Responsible Party):
Kartos Therapeutics, Inc.
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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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Relapsed or Refractory Acute Myeloid Leukemia (AML) Acute Myeloid Leukemia (AML), Secondary to Myeloproliferative Neoplasms (MPN) | Drug: KRT-232 Drug: Cytarabine Drug: Decitabine | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 86 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel 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 When Administered Alone and in Combination 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 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Familial acute myeloid leukemia with mutated CEBPA
Cytogenetically normal acute myeloid leukemia
Core binding factor acute myeloid leukemia
| Arm | Intervention/treatment |
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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. |
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:
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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. |
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 |
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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. |
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 |
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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
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Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth. |
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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.
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Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth. |
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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.
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Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth. |
Primary Outcome Measures :
- 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
Secondary Outcome Measures :
- 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
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| 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 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
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
| Contact: John Mei | 650-542-0136 | jmei@kartosthera.com | |
| Contact: Timothy Sbardellati | tsbardellati@kartosthera.com |
Locations
Show 61 study locations
Sponsors and Collaborators
Kartos Therapeutics, Inc.
| Responsible Party: | Kartos Therapeutics, Inc. |
| ClinicalTrials.gov Identifier: | NCT04113616 |
| Other Study ID Numbers: |
KRT-232-104 |
| First Posted: | October 3, 2019 Key Record Dates |
| Last Update Posted: | August 4, 2022 |
| Last Verified: | August 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Kartos Therapeutics, Inc.:
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navtemadlin |
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 |