Clinical trial NCT06001788: Safety and Tolerability of Ziftomenib Combinations in Patients With Relapsed/Refractory Acute Myeloid Leukemia
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: AML
AML With Mutated NPM1
Hematologic Malignancy
KMT2Ar
NPM1 Mutation
MLL Rearrangement
Leukemia
Acute Myeloid Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Acute Leukemia
Neoplasms by Histologic Type
Lead sponsor: Kura Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2023-08-21
Enrollment: 171
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Rate of dose limiting toxicities (DLTs) per dose level
timeFrame: During the first 28 days of ziftomenib in combination with SOC treatment (1 cycle)
measure: 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
Secondary outcomes:
measure: Complete remission (CR) rate for cohorts A-1, A-2, B-1, and B-2
timeFrame: Up to 12 months following discontinuation of treatment
measure: Complete remission (CR) / Complete remission with partial hematologic recovery (CRh) rate for cohort A-3
timeFrame: Up to 12 months following discontinuation of treatment
measure: Composite complete remission (CRc) rate
timeFrame: Up to 12 months following discontinuation of treatment
measure: Morphologic leukemia-free state (MLFS) rate
timeFrame: Up to 12 months following discontinuation of treatment
measure: OS
timeFrame: Up to 12 months following discontinuation of treatment
measure: 6-month OS
timeFrame: Up to 6 months following discontinuation of treatment
measure: Median EFS
timeFrame: Up to 12 months following discontinuation of treatment
measure: 6-month EFS
timeFrame: Up to 6 months following discontinuation of treatment
measure: DOR
timeFrame: Up to 12 months following discontinuation of treatment
measure: MRD assessment
timeFrame: Up to 12 months following discontinuation of treatment
measure: HSCT
timeFrame: Up to 12 months following discontinuation of treatment
measure: Transfusion independence
timeFrame: Up to 12 months following discontinuation of treatment
measure: Ziftomenib Cmax
timeFrame: Cycle 1 (Each cycle is 28 days)
measure: Ziftomenib Tmax
timeFrame: Cycle 1 (Each cycle is 28 days)
measure: Ziftomenib AUC(0-last)
timeFrame: Cycle 1 (Each cycle is 28 days)
measure: Ziftomenib AUC(tau)
timeFrame: Cycle 1 (Each cycle is 28 days)
measure: Gilteritinib Cmax
timeFrame: Cycle 1 (Each cycle is 28 days)
measure: Gilteritinib Tmax
timeFrame: Cycle 1 (Each cycle is 28 days)
measure: Gilteritinib AUC(0-last)
timeFrame: Cycle 1 (Each cycle is 28 days)
measure: Gilteritinib AUC(tau)
timeFrame: Cycle 1 (Each cycle is 28 days)
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA Health - Bowyer Oncology Center
state: California
city: Orange
country: United States
facility: UCI Health Chao Family Comprehensive Cancer Center
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale New Haven
state: Connecticut
city: Kansas City
country: United States
facility: The University of Kansas
state: Kansas
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Cancer Institute
state: Michigan
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook Cancer Center
state: New York
city: Charlotte
country: United States
facility: Atrium Health Levine Cancer Center
state: North Carolina
city: Oklahoma City
country: United States
facility: OU Health Stephenson Cancer Center
state: Oklahoma
city: Allentown
country: United States
facility: Lehigh Valley Topper Cancer Institute
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health
state: South Carolina
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria do Bologna - Policlinico di Sant'Orsola
city: Ravenna
country: Italy
facility: Ospedale Santa Maria delle Croci
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Valencia
country: Spain
facility: Hospital Universitari y Politecnic La Fe
Study officials:
affiliation: Kura Oncology
name: Clinical Development
role: STUDY_DIRECTOR
References: