Safety and Tolerability of Ziftomenib Combinations in Patients With Relapsed/Refractory Acute Myeloid Leukemia

NCT06001788
clinicaltrials.gov
Phase
Phase 1
clinicaltrials.gov
Recruitment status
Recruiting
clinicaltrials.gov
Participants
171
clinicaltrials.gov
Lead sponsor
Kura Oncology, Inc.
clinicaltrials.gov
Start date
2024-02-22
clinicaltrials.gov
Number of sites
45
clinicaltrials.gov

Summary
The safety, tolerability, and antileukemic response of ziftomenib in combination with standard of care treatments for patients with relapsed/refractory acute myeloid leukemia will be examined with the following agents: FLAG-IDA, low-dose cytarabine, and gilteritinib.
clinicaltrials.gov
Short title
Safety and Tolerability of Ziftomenib Combinations in Patients With Relapsed/Refractory Acute Myeloid Leukemia
clinicaltrials.gov
Official title
Phase 1 Study to Determine the Safety and Tolerability of Ziftomenib Combinations for the Treatment of KMT2A-rearranged or NPM1-mutant Relapsed/Refractory Acute Myeloid Leukemia
clinicaltrials.gov

Control arm
Open label
clinicaltrials.gov
Registry reports results
No
clinicaltrials.gov
Listing at source
Listed
clinicaltrials.gov
Recruitment status
Recruiting
clinicaltrials.gov
Phase
Phase 1
clinicaltrials.gov
Study type
Interventional
clinicaltrials.gov

Completion date
2027-08-01
clinicaltrials.gov
First posted
2023-08-21
clinicaltrials.gov
Registry last updated
2026-08-20
clinicaltrials.gov
Primary completion date
2026-12-01
clinicaltrials.gov
Start date
2024-02-22
clinicaltrials.gov

Participants
171
clinicaltrials.gov
Participant count basis
Estimated
clinicaltrials.gov
Planned participants
171
clinicaltrials.gov
Protocol amendments
4
clinicaltrials.gov
Number of sites
45
clinicaltrials.gov

Data monitoring committee
Yes
clinicaltrials.gov
Registry sponsor category
Industry
clinicaltrials.gov
Lead sponsor
Kura Oncology, Inc.
clinicaltrials.gov
Source registry
ClinicalTrials.gov
clinicaltrials.gov

Registry ID
NCT06001788
clinicaltrials.gov
ClinicalTrials.gov ID
NCT06001788
clinicaltrials.gov
Registry record
Open registry record
clinicaltrials.gov

Allocation
Not randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Rate of dose limiting toxicities (DLTs) per dose level

    Timeframe: During the first 28 days of ziftomenib in combination with SOC treatment (1 cycle)

    Assessed by the NCI-CTCAE v5.0

  2. Descriptive statistics of adverse events

    Timeframe: 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

  1. Complete remission (CR) rate for cohorts A-1, A-2, B-1, and B-2

    Timeframe: Up to 12 months following discontinuation of treatment

    Assessed by ELN 2022 criteria

  2. Complete remission (CR) / Complete remission with partial hematologic recovery (CRh) rate for cohort A-3

    Timeframe: Up to 12 months following discontinuation of treatment

    Assessed by ELN 2022 criteria

  3. Composite complete remission (CRc) rate

    Timeframe: Up to 12 months following discontinuation of treatment

    Assessed by ELN 2022 criteria

  4. Morphologic leukemia-free state (MLFS) rate

    Timeframe: Up to 12 months following discontinuation of treatment

    Assessed by ELN 2022 criteria

  5. OS

    Timeframe: Up to 12 months following discontinuation of treatment

    To assess overall survival

  6. 6-month OS

    Timeframe: Up to 6 months following discontinuation of treatment

    To assess proportion of patients alive at 6 months

  7. Median EFS

    Timeframe: Up to 12 months following discontinuation of treatment

    To assess median event free survival

  8. 6-month EFS

    Timeframe: Up to 6 months following discontinuation of treatment

    To assess 6-month event free survival

  9. DOR

    Timeframe: Up to 12 months following discontinuation of treatment

    To assess duration of remission

  10. MRD assessment

    Timeframe: Up to 12 months following discontinuation of treatment

    To assess minimum residual disease in bone marrow as assessed by multiparameter flow cytometry (MFC) and molecular analysis

  11. HSCT

    Timeframe: Up to 12 months following discontinuation of treatment

    To assess proportion of patients that undergo a hematopoietic stem-cell transplant

  12. Transfusion independence

    Timeframe: Up to 12 months following discontinuation of treatment

    To assess rate of transfusion independence

  13. Ziftomenib Cmax

    Timeframe: Cycle 1 (Each cycle is 28 days)

    To assess the maximum plasma combination of ziftomenib and its metabolites

  14. Ziftomenib Tmax

    Timeframe: Cycle 1 (Each cycle is 28 days)

    To assess the time to observed maximum plasma concentration of ziftomenib and its metabolites

  15. Ziftomenib AUC(0-last)

    Timeframe: Cycle 1 (Each cycle is 28 days)

    To assess the area under the plasma concentration-time-curve from time 0 to time of last measurable concentration of ziftomenib and its metabolites

  16. Ziftomenib AUC(tau)

    Timeframe: Cycle 1 (Each cycle is 28 days)

    To assess the area under the plasma concentration-time-curve over a dosing interval for ziftomenib and its metabolites

  17. Gilteritinib Cmax

    Timeframe: Cycle 1 (Each cycle is 28 days)

    To assess the maximum plasma combination of gilteritinib

  18. Gilteritinib Tmax

    Timeframe: Cycle 1 (Each cycle is 28 days)

    To assess the time to observed maximum plasma concentration of gilteritinib

  19. Gilteritinib AUC(0-last)

    Timeframe: Cycle 1 (Each cycle is 28 days)

    To assess the area under the plasma concentration-time-curve from time 0 to time of last measurable concentration of gilteritinib

  20. Gilteritinib AUC(tau)

    Timeframe: Cycle 1 (Each cycle is 28 days)

    To assess the area under the plasma concentration-time-curve over a dosing interval for gilteritinib

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

Key Inclusion Criteria:

  • Has been diagnosed with relapsed/refractory AML.
  • Has a documented NPM1 mutation or KMT2A rearrangement.
  • Has a documented FLT3 mutation (cA-3 only).
  • Has an Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2.
  • Has adequate hepatic and renal function as defined per protocol.
  • Has an ejection fraction above a protocol defined limit.
  • Participant, or legally authorized representative, must be able to understand and provide written informed consent prior to the first screening procedure.
  • Has agreed to use contraception as defined per protocol.

Key Exclusion Criteria:

  • Has a diagnosis of acute promyelocytic leukemia or blast chronic myeloid leukemia.
  • Has clinically active central nervous system leukemia.
  • Has an active and uncontrolled infection.
  • Has a mean corrected QT interval (QTcF) > 480ms.
  • Has uncontrolled intercurrent illness, including, but not limited to protocol defined cardiac disease.
  • Has received radiation, chemotherapy, immunotherapy, or any other anticancer therapy including investigational therapy <14 days or within 5 drug half-lives prior to the first dose of study intervention.
  • Has had major surgery within 4 weeks prior to the first dose of study intervention.
  • Has received a hematopoietic stem cell transplant (HSCT) and has not previously had adequate recovery per protocol defined criteria.
  • Has active graft-versus-host disease (GvHD) and or on immunosuppressive drugs for the treatment of GvHD
  • Participant is pregnant or lactating.
Sources for eligibility
clinicaltrials.gov

  • Banner MD Anderson Cancer CenterGilbert, United StatesRecruiting
  • USC Norris Comprehensive Cancer CenterLos Angeles, United StatesRecruiting
  • UCLA Health - Bowyer Oncology CenterLos Angeles, United StatesRecruiting
  • UC Irvine Health Chao Family Comprehensive Cancer CenterOrange, United StatesRecruiting
  • University of California San FranciscoSan Francisco, United StatesRecruiting
  • Colorado Blood Cancer InstituteDenver, United StatesRecruiting
  • Smilow Cancer Hospital at Yale New HavenNew Haven, United StatesRecruiting
  • Emory Healthcare - The Emory ClinicAtlanta, United StatesRecruiting
  • Georgia Cancer Center at Augusta UniversityAugusta, United StatesRecruiting
  • Robert H. Lurie Comprehensive Cancer Center of Northwestern UniversityChicago, United StatesRecruiting
  • Loyola University Medical CenterMaywood, United StatesRecruiting
  • Simmons Cancer InstituteSpringfield, United StatesWithdrawn
  • University of Iowa Hospitals & ClinicsIowa City, United StatesRecruiting
  • The University of Kansas Cancer CenterKansas City, United StatesRecruiting
  • Beth Israel Deaconess Medical CenterBoston, United StatesRecruiting
  • Karmanos Cancer InstituteDetroit, United StatesRecruiting
  • Henry Ford Cancer InstituteDetroit, United StatesRecruiting
  • Washington University School of MedicineSt Louis, United StatesRecruiting
  • University of Nebraska Medical CenterOmaha, United StatesRecruiting
  • John Theurer Cancer Center at Hackensack University Medical CenterHackensack, United StatesRecruiting
  • Roswell Park Comprehensive Cancer CenterBuffalo, United StatesRecruiting
  • Northwell Health, LLC PRIMELake Success, United StatesRecruiting
  • Memorial Sloan Kettering Cancer CenterNew York, United StatesRecruiting
  • Weill Cornell Medical College-NY Presbyterian HospitalNew York, United StatesRecruiting
  • Wilmot Cancer Institute, University of RochesterRochester, United StatesRecruiting

And 20 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

Related records

Drugs (6)

Lead sponsors (1)

Conditions (6)

Targets (17)