A Study to Investigate the Safety and Tolerability of Ziftomenib in Combination With Venetoclax/Azacitidine, Venetoclax, or 7+3 in Patients With AML
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| ClinicalTrials.gov Identifier: NCT05735184 |
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Recruitment Status :
Recruiting
First Posted : February 21, 2023
Last Update Posted : May 16, 2024
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Sponsor:
Kura Oncology, Inc.
Information provided by (Responsible Party):
Kura Oncology, Inc.
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Brief Summary:
This Phase 1 study will assess the safety, tolerability, and preliminary antileukemic activity of ziftomenib in combination with venetoclax and azacitidine (ven/aza), ven, and 7+3 for two different molecularly-defined arms, NPM1-m and KMT2A-r.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Acute Myeloid Leukemia Mixed Lineage Acute Leukemia Mixed Lineage Leukemia Gene Mutation Mixed Phenotype Acute Leukemia Refractory AML AML With Mutated NPM1 Acute Myeloid Leukemia Recurrent Acute Myeloid Leukemia, in Relapse NPM1 Mutation KMT2Ar Myeloid Sarcoma | Drug: Ziftomenib Drug: Venetoclax Drug: Azacitidine Drug: Daunorubicin Drug: Cytarabine | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 212 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase 1 Study of Venetoclax/Azacitidine or Venetoclax in Combination With Ziftomenib or Standard Induction Cytarabine/Daunorubicin (7+3) Chemotherapy in Combination With Ziftomenib for the Treatment of Patients With Acute Myeloid Leukemia |
| Actual Study Start Date : | July 18, 2023 |
| Estimated Primary Completion Date : | May 2026 |
| Estimated Study Completion Date : | May 2027 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Dose Escalation: Ziftomenib/Venetoclax/Azacitidine in R/R NPM1-m (A-1)
Ziftomenib/Venetoclax/Azacitidine in relapsed/refractory NPM1-m AML patients who have failed at least one prior line of therapy
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Drug: Ziftomenib
Oral Administration Drug: Venetoclax Oral Administration Drug: Azacitidine Subcutaneous or Intravenous Administration |
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Experimental: Dose Escalation: Ziftomenib/7+3 in 1L NPM1-m (A-2)
Ziftomenib/7+3 in newly diagnosed NPM1-m AML patients who are candidates for intensive chemotherapy and meet the protocol definition of high-risk disease
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Drug: Ziftomenib
Oral Administration Drug: Daunorubicin Intravenous Administration Drug: Cytarabine Intravenous Administration |
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Experimental: Dose Escalation: Ziftomenib/Venetoclax/Azacitidine in R/R KMT2A-r (B-1)
Ziftomenib/Venetoclax/Azacitidine in relapsed/refractory KMT2A-r AML patients who have failed at least one prior line of therapy
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Drug: Ziftomenib
Oral Administration Drug: Venetoclax Oral Administration Drug: Azacitidine Subcutaneous or Intravenous Administration |
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Experimental: Dose Escalation: Ziftomenib/7+3 in 1L KMT2A-r (B-2)
Ziftomenib/7+3 in newly diagnosed KMT2A-r AML patients who are candidates for intensive chemotherapy and meet the protocol definition of high-risk disease
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Drug: Ziftomenib
Oral Administration Drug: Daunorubicin Intravenous Administration Drug: Cytarabine Intravenous Administration |
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Experimental: Dose Validation/Expansion: Ziftomenib/Venetoclax/Azacitidine in R/R NPM1-m (A-1)
Ziftomenib/Venetoclax/Azacitidine in relapsed/refractory NPM1-m AML patients who have failed at least one prior line of therapy
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Drug: Ziftomenib
Oral Administration Drug: Venetoclax Oral Administration Drug: Azacitidine Subcutaneous or Intravenous Administration |
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Experimental: Dose Validation/Expansion: Ziftomenib/7+3 in 1L NPM1-m (A-2)
Ziftomenib/7+3 in newly diagnosed NPM1-m AML patients who are candidates for intensive chemotherapy and meet the protocol definition of high-risk disease
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Drug: Ziftomenib
Oral Administration Drug: Daunorubicin Intravenous Administration Drug: Cytarabine Intravenous Administration |
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Experimental: Dose Validation/Expansion: Ziftomenib/Venetoclax in R/R NPM1-m (A-3)
Ziftomenib/Venetoclax in relapsed/refractory NPM1-m AML patients who have failed at least one prior line of therapy
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Drug: Ziftomenib
Oral Administration Drug: Venetoclax Oral Administration |
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Experimental: Dose Validation/Expansion: Ziftomenib/Venetoclax/Azacitidine in 1L NPM1-m (A-4)
Ziftomenib/Venetoclax/Azacitidine in newly diagnosed NPM1-m AML patients
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Drug: Ziftomenib
Oral Administration Drug: Venetoclax Oral Administration Drug: Azacitidine Subcutaneous or Intravenous Administration |
|
Experimental: Dose Validation/Expansion: Ziftomenib/Venetoclax/Azacitidine in R/R KMT2A-r (B-1)
Ziftomenib/Venetoclax/Azacitidine in relapsed/refractory KMT2A-r AML patients who have failed at least one prior line of therapy
|
Drug: Ziftomenib
Oral Administration Drug: Venetoclax Oral Administration Drug: Azacitidine Subcutaneous or Intravenous Administration |
|
Experimental: Dose Validation/Expansion: Ziftomenib/7+3 in 1L KMT2A-r (B-2)
Ziftomenib/7+3 in newly diagnosed KMT2A-r AML patients who are candidates for intensive chemotherapy
|
Drug: Ziftomenib
Oral Administration Drug: Daunorubicin Intravenous Administration Drug: Cytarabine Intravenous Administration |
|
Experimental: Dose Validation/Expansion: Ziftomenib/Venetoclax/Azacitidine in 1L KMT2A-r (B-3)
Ziftomenib/Venetoclax/Azacitidine in newly diagnosed KMT2A-r AML patients
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Drug: Ziftomenib
Oral Administration Drug: Venetoclax Oral Administration Drug: Azacitidine Subcutaneous or Intravenous Administration |
Primary Outcome Measures :
- Rate of dose limiting toxicities (DLTs) per dose level [ Time Frame: During the first 28 days of ziftomenib in combination with SOC backbone treatment (1 cycle) ]Assessed by the NCI-CTCAE v5.0
- Descriptive statistics of adverse events [ Time Frame: First dose of ziftomenib up to and including 28 days after last dose of ziftomenib, or if the patient is lost to follow-up, whichever comes first ]Assessed by the NCI-CTCAE v5.0
- Complete remission (CR) rate [ Time Frame: Up to 1 year following end of treatment with ziftomenib ]Assessed by the ELN 2022 criteria
Secondary Outcome Measures :
- Composite Complete Remission (CRc) or MLFS rate [ Time Frame: Up to 1 year following end of treatment with ziftomenib ]Assessed by the ELN 2022 criteria
- Measurable residual disease (MRD) [ Time Frame: Up to 1 year following end of treatment with ziftomenib ]Assessed by multiparameter flow cytometry (MFC) and molecular analysis
- Median OS [ Time Frame: Up to 1 year following end of treatment with ziftomenib ]To assess overall survival of ziftomenib
- Proportion of patients alive [ Time Frame: 1 year following end of treatment with ziftomenib ]To assess proportion of patients alive at 1 year following treatment with ziftomenib
- Median EFS [ Time Frame: Up to 1 year following end of treatment with ziftomenib ]To assess median event free survival
- EFS [ Time Frame: 1 year following end of treatment with ziftomenib ]To assess event free survival
- Median DOR [ Time Frame: Up to 1 year following end of treatment with ziftomenib ]To assess median duration of remission
- Proportion of patients who undergo HSCT [ Time Frame: Up to 1 year following end of treatment with ziftomenib ]To assess proportion of patients who undergo hematopoietic stem cell transplant
- TI [ Time Frame: Up to 1 year following end of treatment with ziftomenib ]To assess rate of transfusion independence
- Cmax [ Time Frame: Cycle 1. Each cycle is 28 days. ]Maximum plasma concentration (Cmax) of ziftomenib and metabolites
- Tmax [ Time Frame: Cycle 1. Each cycle is 28 days. ]Time to maximum plasma concentration (Tmax) of ziftomenib and metabolites
- AUC0-last [ Time Frame: Cycle 1. Each cycle is 28 days. ]Area under the concentration-time curve from time zero to the time of the last quantifiable concentration after dosing (AUC0-last) of ziftomenib and metabolites
- AUCtau [ Time Frame: Cycle 1. Each cycle is 28 days. ]Area under the concentration-time curve over a dosing interval (AUCtau) of ziftomenib
- Accumulation ratio of ziftomenib and metabolites [ Time Frame: Cycle 1. Each cycle is 28 days. ]To assess accumulation ratio of ziftomenib and metabolites
- Cmax of venetoclax [ Time Frame: Cycle 1. Each cycle is 28 days. ]Maximum plasma concentration (Cmax) of venetoclax
- Tmax of venetoclax [ Time Frame: Cycle 1. Each cycle is 28 days. ]Time to maximum plasma concentration (Tmax) of venetoclax
- AUC0-last of venetoclax [ Time Frame: Cycle 1. Each cycle is 28 days. ]Area under the concentration-time curve from time zero to the time of the last quantifiable concentration after dosing (AUC0-last) of venetoclax
- AUCtau of venetoclax [ Time Frame: Cycle 1. Each cycle is 28 days. ]Area under the concentration-time curve over a dosing interval (AUCtau) of venetoclax
Information from the National Library of Medicine
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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:
- Patients must have a documented NPM1 mutation or KMT2A rearrangement and have either newly diagnosed or relapsed/refractory AML
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Adequate liver, renal, and cardiac function according to protocol defined criteria
- A female of childbearing potential must agree to use adequate contraception from the time of screening through 180 days following the last dose of study intervention. A male of childbearing potential must agree to use abstinence or adequate contraception from the time of screening through 90 days following the last dose of study intervention
Key Exclusion Criteria:
- Diagnosis of either acute promyelocytic leukemia or blast chronic myelomonocytic leukemia
- Known history of BCR-ABL alteration
- Advanced malignant hepatic tumor [for patients receiving ven/aza combination]
- Administration of live attenuated vaccines within 14 days prior to, during, or after treatment until B-cell recovery
- Active central nervous system (CNS) involvement by AML.
- Clinical signs/symptoms of leukostasis or WBC > 25,000 / microliter. Hydroxyurea and/or leukapheresis are permitted to meet this criterion
- Not recovered to Grade ≤1 (NCI-CTCAE v5.0) from all nonhematological toxicities except for alopecia
- Known clinically active human immunodeficiency virus, active hepatitis B or active hepatitis C infection
- For newly diagnosed cohorts: received prior chemotherapy for leukemia, except hydroxyurea and/or leukapheresis to control leukocytosis, prior treatment with all-transretinoic acid for initially suspected acute promyelocytic leukemia, or non-HMA therapy for prior myelodysplastic syndrome
- For relapsed/refractory cohorts: received chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy that is considered to be investigational < 14 days prior to the first dose of ziftomenib or within 5 drug half-lives prior to the first dose of study drug
- Uncontrolled intercurrent illness including, but not limited to, cardiac illness as defined in the protocol
- Mean corrected QT interval corrected for heart rate by Fredericia's formula (QTcF) >480 ms on triplicate ECGs
- Uncontrolled infection
- Women who are pregnant or lactating
- An active malignancy and currently receiving chemotherapy for that malignancy or disease that is uncontrolled/progressing
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): NCT05735184
Contacts
| Contact: Clinical Operations | 858 500 8800 | KO-MEN-007@kuraoncology.com |
Locations
Show 28 study locations
Sponsors and Collaborators
Kura Oncology, Inc.
| Responsible Party: | Kura Oncology, Inc. |
| ClinicalTrials.gov Identifier: | NCT05735184 |
| Other Study ID Numbers: |
KO-MEN-007 |
| First Posted: | February 21, 2023 Key Record Dates |
| Last Update Posted: | May 16, 2024 |
| Last Verified: | May 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| 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 Sarcoma, Myeloid Leukemia, Biphenotypic, Acute Acute Disease Neoplasms by Histologic Type Neoplasms Hematologic Diseases Sarcoma Neoplasms, Connective and Soft Tissue Disease Attributes Pathologic Processes Leukemia, Lymphoid Lymphoproliferative Disorders |
Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Cytarabine Azacitidine Venetoclax Daunorubicin Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antiviral Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors |