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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06001788
• Other study ID #: KO-MEN-008
• Status: Recruiting
• Phase: Phase 1
• Start date: February 22, 2024
• Est. completion date: August 2027

Study information

• Verified date: April 2024
• Source: Kura Oncology, Inc.
• Contact: Clinical Operations
• Phone: 858 500 8800
• Email: KO-MEN-008[@]kuraoncology.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 171
• Est. completion date: August 2027
• Est. primary completion date: August 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Has been diagnosed with relapsed/refractory AML.
• Has a documented NPM1 mutation or KMT2A rearrangement.
• Has a documented FLT3 mutation (cohort A-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.

Related Conditions & MeSH terms

• Acute Leukemia
• Acute Myeloid Leukemia
• AML
• Hematologic Malignancy
• Hematologic Neoplasms
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Neoplasms by Histologic Type

Intervention

Drug:
• Ziftomenib
Oral administration
• Fludarabine
Intravenous infusion
• Idarubicin
Intravenous infusion
• Cytarabine
Intravenous Infusion
• Gilteritinib
Oral administration

Biological:
• Granulocyte colony-stimulating factor
Subcutaneous injection

Locations

Country	Name	City	State
United States	Henry Ford Cancer Institute	Detroit	Michigan
United States	Prisma Health	Greenville	South Carolina
United States	The University of Kansas	Kansas City	Kansas
United States	Smilow Cancer Hospital at Yale New Haven	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Kura Oncology, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of dose limiting toxicities (DLTs) per dose level	Assessed by the NCI-CTCAE v5.0	During the first 28 days of ziftomenib in combination with SOC treatment (1 cycle)
Primary	Descriptive statistics of adverse events	Assessed by the NCI-CTCAE v5.0	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
Secondary	Complete remission (CR) rate for cohorts A-1, A-2, B-1, and B-2	Assessed by ELN 2022 criteria	Up to 12 months following discontinuation of treatment
Secondary	Complete remission (CR) / Complete remission with partial hematologic recovery (CRh) rate for cohort A-3	Assessed by ELN 2022 criteria	Up to 12 months following discontinuation of treatment
Secondary	Composite complete remission (CRc) rate	Assessed by ELN 2022 criteria	Up to 12 months following discontinuation of treatment
Secondary	Morphologic leukemia-free state (MLFS) rate	Assessed by ELN 2022 criteria	Up to 12 months following discontinuation of treatment
Secondary	OS	To assess overall survival	Up to 12 months following discontinuation of treatment
Secondary	6-month OS	To assess proportion of patients alive at 6 months	Up to 6 months following discontinuation of treatment
Secondary	Median EFS	To assess median event free survival	Up to 12 months following discontinuation of treatment
Secondary	6-month EFS	To assess 6-month event free survival	Up to 6 months following discontinuation of treatment
Secondary	DOR	To assess duration of remission	Up to 12 months following discontinuation of treatment
Secondary	MRD assessment	To assess minimum residual disease in bone marrow as assessed by multiparameter flow cytometry (MFC) and molecular analysis	Up to 12 months following discontinuation of treatment
Secondary	HSCT	To assess proportion of patients that undergo a hematopoietic stem-cell transplant	Up to 12 months following discontinuation of treatment
Secondary	Transfusion independence	To assess rate of transfusion independence	Up to 12 months following discontinuation of treatment
Secondary	Ziftomenib Cmax	To assess the maximum plasma combination of ziftomenib and its metabolites	Cycle 1 (Each cycle is 28 days)
Secondary	Ziftomenib Tmax	To assess the time to observed maximum plasma concentration of ziftomenib and its metabolites	Cycle 1 (Each cycle is 28 days)
Secondary	Ziftomenib AUC(0-last)	To assess the area under the plasma concentration-time-curve from time 0 to time of last measurable concentration of ziftomenib and its metabolites	Cycle 1 (Each cycle is 28 days)
Secondary	Ziftomenib AUC(tau)	To assess the area under the plasma concentration-time-curve over a dosing interval for ziftomenib and its metabolites	Cycle 1 (Each cycle is 28 days)
Secondary	Gilteritinib Cmax	To assess the maximum plasma combination of gilteritinib	Cycle 1 (Each cycle is 28 days)
Secondary	Gilteritinib Tmax	To assess the time to observed maximum plasma concentration of gilteritinib	Cycle 1 (Each cycle is 28 days)
Secondary	Gilteritinib AUC(0-last)	To assess the area under the plasma concentration-time-curve from time 0 to time of last measurable concentration of gilteritinib	Cycle 1 (Each cycle is 28 days)
Secondary	Gilteritinib AUC(tau)	To assess the area under the plasma concentration-time-curve over a dosing interval for gilteritinib	Cycle 1 (Each cycle is 28 days)