AMLPhase 1NCT06001788
Safety and Tolerability of Ziftomenib Combinations in Patients With Relapsed/Refractory Acute Myeloid Leukemia
A Phase 1 study testing Ziftomenib, Fludarabine and Idarubicin in people with AML and AML With Mutated NPM1, run by Kura Oncology, Inc. at 45 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- AML, AML With Mutated NPM1, Hematologic Malignancy
- What is being tested?
- Ziftomenib, Fludarabine and Idarubicin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 171 participants
- Where
- 45 sitesin 3 countries
- Study dates
- 22 Feb 2024to Aug 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
45 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
45 sites in 3 countries
United States38 sites, 36 recruiting
- Withdrawn
Lehigh Valley Topper Cancer Institute
Allentown, Pennsylvania, 18103
- Recruiting
Emory Healthcare - The Emory Clinic
Atlanta, Georgia, 30322
Gigi Stoneback, gissela.blanco.stoneback@emory.edu
- Recruiting
Georgia Cancer Center at Augusta University
Augusta, Georgia, 30912
Amanda Spires, amspires@augusta.edu
- Recruiting
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
- Recruiting
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14263
877-275-7724, askrpci@roswellpark.org
- Recruiting
University of Vermont
Burlington, Vermont, 05401
Stephanie Stahl, 802-656-2021, Stephanie.Stahl@uvmhealth.org
- Recruiting
Atrium Health Levine Cancer Center
Charlotte, North Carolina, 60201
Chari Granger, Chari.Granger@atriumhealth.org
- Recruiting
University of Virginia Comprehensive Cancer Center
Charlottesville, Virginia, 22903
Avani Hopkins, 434-243-8108, Ajh7jqe@uvahealth.org
- Recruiting
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago, Illinois, 60611
312-695-9367, cancer@northwestern.edu
- Recruiting
UH Seidman Cancer Center
Cleveland, Ohio, 44106
Leslie Ortega, 216-844-8129, ctgov@case.edu
- Recruiting
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246
Christine Terraciano, Christine.Terraciano@usoncology.com
- Recruiting
Colorado Blood Cancer Institute
Denver, Colorado, 80218
New Patient Contact, 720-754-4835, PLSMDLCBCINewPatient@HCAHealthcare.com
- Recruiting
Karmanos Cancer Institute
Detroit, Michigan, 48201
- Recruiting
Henry Ford Cancer Institute
Detroit, Michigan, 48202
Kristyn Dailey, KDailey6@hfhs.org
- Recruiting
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234
480-256-6444, BMDACCResearch@bannerhealth.com
- Recruiting
Prisma Health
Greenville, South Carolina, 29615
Lisa Johnson, 864-455-3735, lisa.johnson@prismahealth.org
Fiona Davidson, 864-455-3737, fiona.davidson@prismahealth.org
- Recruiting
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601
Oncology Clinical Reference Referral Office, 551-996-1777, OncologyResearchReferral@hmhn.org
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Ann Mosely, aemosley@mdanderson.org
- Recruiting
University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242
Grerk Sutamtewagul, 319-353-8383, Grerk-sutamtewagul@uiowa.edu
- Recruiting
The University of Kansas Cancer Center
Kansas City, Kansas, 66160
KUCC Navigation Team, 913-588-3671, kucc_navigation@kumc.edu
- Recruiting
Northwell Health, LLC PRIME
Lake Success, New York, 11042
- Recruiting
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90089
Christine Duran, 323-865-0371, duran_c@med.usc.edu
- Recruiting
UCLA Health - Bowyer Oncology Center
Los Angeles, California, 90095
Bruck Habtemariam, 310-794-0242, bhabtemariam@mednet.ucla.edu
- Recruiting
Loyola University Medical Center
Maywood, Illinois, 60153
Esteban Orozco Espiricueta, 708-327-3221, eespiricuetaorozco@luc.edu
- Recruiting
Froedtert & Medical College Clinics
Milwaukee, Wisconsin, 53226
- Recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Recruitment and Eligibility Office, 800-811-8480, cip@vumc.org
- Recruiting
Smilow Cancer Hospital at Yale New Haven
New Haven, Connecticut, 06511
Farah Fasihuddin, 203-737-3472, farah.fasihuddin@yale.edu
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10021
646-888-4167
- Recruiting
Weill Cornell Medical College-NY Presbyterian Hospital
New York, New York, 10065
Tania Curcio, 212-746-2571, tjc9003@med.cornell.edu
- Recruiting
OU Health Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Cynthia J Lowery, Cynthia-Lowery@ouhsc.edu
- Recruiting
University of Nebraska Medical Center
Omaha, Nebraska, 68198
- Recruiting
UC Irvine Health Chao Family Comprehensive Cancer Center
Orange, California, 92868
Research Line, 877-827-8839, ucstudy@hs.uci.edu
- Recruiting
Wilmot Cancer Institute, University of Rochester
Rochester, New York, 14642
Clinical Trials Referral Office, 855-776-0015, wcictoresearch@urmc.rochester.edu
- Recruiting
University of California San Francisco
San Francisco, California, 94115
- Recruiting
University of Washington
Seattle, Washington, 98109
- Withdrawn
Simmons Cancer Institute
Springfield, Illinois, 62702
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
- Recruiting
Stony Brook Cancer Center
Stony Brook, New York, 11794
Zita Makselyte, zita.makselyte@stonybrookmedicine.edu
Spain4 sites, 4 recruiting
- Recruiting
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Olga Salamero, 34932746100 ext. 4894, osalamero@vhio.net
- Recruiting
Hospital Universitario Central de Asturias
Oviedo, 33011
Teresa Bernal del Castillo, 34618753904, Bernaldelcastillo@gmail.com
- Recruiting
Hospital Universitario Virgen del Rocío
Seville, 41013
Eduardo Rodríguez-Arbolí, 34955013277, edurodarb@gmail.com
- Recruiting
Hospital Universitari y Politecnic La Fe
Valencia, 46026
Pau Montesinos Fernandez, 34961244925, montesinos_pau@gva.es
Italy3 sites, 3 recruiting
- Recruiting
IRCCS Azienda Ospedaliero-Universitaria do Bologna - Policlinico di Sant'Orsola
Bologna, 40138
Cristina Papayannidis, 39512144177, cristina.papayannidis@unibo.it
- Recruiting
Ospedale Santa Maria delle Croci
Ravenna, 48121
Francesco Lanza, 390544285734, francesco.lanza@auslromagna.it
- Recruiting
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Roma, 00168
Simona Sica, 390635503953, simona.sica@unicatt.it
About this study
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
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.
- Conditions
- AML, AML With Mutated NPM1, Hematologic Malignancy, KMT2Ar, NPM1 Mutation, MLL Rearrangement
- Being tested
- Ziftomenib, Fludarabine, Idarubicin, Cytarabine, Gilteritinib
- Medical subject headings
- Hematologic Neoplasms, Leukemia, Leukemia, Myeloid, Acute, Leukemia, Myeloid, Neoplasms by Histologic Type
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZiftomenibDrug
Also called KO-539
Oral administration
FludarabineDrug
Intravenous infusion
IdarubicinDrug
Intravenous infusion
CytarabineDrug
Intravenous Infusion
GilteritinibDrug
Also called Xospata
Oral administration
Granulocyte colony-stimulating factorBiological
Subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Phase 1a | Experimental | Oral ziftomenib; sequential cohorts of escalating dose levels of ziftomenib to identify the safety and tolerability of the combination regimens. Participants will be enrolled in 1 of 5 dose escalation cohorts:
A-1: Participants with a NPM1 mutation: ziftomenib plus FLAG-IDA
A-2: Participants with a NPM1 mutation: ziftomenib plus low-dose cytarabine (LDAC)
A-3: Participants with a NPM1 mutation: ziftomenib plus gilteritinib
B-1: Participants with a KMT2A rearrangement: ziftomenib plus FLAG-IDA
B-2: Participants with a KMT2A rearrangement: ziftomenib plus low-dose cytarabine (LDAC) Receives: Drug: Ziftomenib; Drug: Fludarabine; Drug: Idarubicin; Drug: Cytarabine; Drug: Gilteritinib; Biological: Granulocyte colony-stimulating factor |
| Phase 1b | Experimental | Oral ziftomenib; Following the determination of the maximum tolerated dose in Phase 1a, participants will be enrolled in 1 of 5 dose validation/expansion cohorts:
A-1: Participants with a NPM1 mutation: ziftomenib plus FLAG-IDA
A-2: Participants with a NPM1 mutation: ziftomenib plus low-dose cytarabine (LDAC)
A-3: Participants with a NPM1 mutation: ziftomenib plus gilteritinib
B-1: Participants with a KMT2A rearrangement: ziftomenib plus FLAG-IDA
B-2: Participants with a KMT2A rearrangement: ziftomenib plus low-dose cytarabine (LDAC) Receives: Drug: Ziftomenib; Drug: Fludarabine; Drug: Idarubicin; Drug: Cytarabine; Drug: Gilteritinib; Biological: Granulocyte colony-stimulating factor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of dose limiting toxicities (DLTs) per dose level
Assessed by the NCI-CTCAE v5.0
Measured: During the first 28 days of ziftomenib in combination with SOC treatment (1 cycle)
Descriptive statistics of adverse events
Assessed by the NCI-CTCAE v5.0
Measured: 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 (20)
Complete remission (CR) rate for cohorts A-1, A-2, B-1, and B-2
Assessed by ELN 2022 criteria
Measured: Up to 12 months following discontinuation of treatment
Complete remission (CR) / Complete remission with partial hematologic recovery (CRh) rate for cohort A-3
Assessed by ELN 2022 criteria
Measured: Up to 12 months following discontinuation of treatment
Composite complete remission (CRc) rate
Assessed by ELN 2022 criteria
Measured: Up to 12 months following discontinuation of treatment
Morphologic leukemia-free state (MLFS) rate
Assessed by ELN 2022 criteria
Measured: Up to 12 months following discontinuation of treatment
OS
To assess overall survival
Measured: Up to 12 months following discontinuation of treatment
6-month OS
To assess proportion of patients alive at 6 months
Measured: Up to 6 months following discontinuation of treatment
Median EFS
To assess median event free survival
Measured: Up to 12 months following discontinuation of treatment
6-month EFS
To assess 6-month event free survival
Measured: Up to 6 months following discontinuation of treatment
DOR
To assess duration of remission
Measured: Up to 12 months following discontinuation of treatment
MRD assessment
To assess minimum residual disease in bone marrow as assessed by multiparameter flow cytometry (MFC) and molecular analysis
Measured: Up to 12 months following discontinuation of treatment
HSCT
To assess proportion of patients that undergo a hematopoietic stem-cell transplant
Measured: Up to 12 months following discontinuation of treatment
Transfusion independence
To assess rate of transfusion independence
Measured: Up to 12 months following discontinuation of treatment
Ziftomenib Cmax
To assess the maximum plasma combination of ziftomenib and its metabolites
Measured: Cycle 1 (Each cycle is 28 days)
Ziftomenib Tmax
To assess the time to observed maximum plasma concentration of ziftomenib and its metabolites
Measured: Cycle 1 (Each cycle is 28 days)
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
Measured: Cycle 1 (Each cycle is 28 days)
Ziftomenib AUC(tau)
To assess the area under the plasma concentration-time-curve over a dosing interval for ziftomenib and its metabolites
Measured: Cycle 1 (Each cycle is 28 days)
Gilteritinib Cmax
To assess the maximum plasma combination of gilteritinib
Measured: Cycle 1 (Each cycle is 28 days)
Gilteritinib Tmax
To assess the time to observed maximum plasma concentration of gilteritinib
Measured: Cycle 1 (Each cycle is 28 days)
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
Measured: Cycle 1 (Each cycle is 28 days)
Gilteritinib AUC(tau)
To assess the area under the plasma concentration-time-curve over a dosing interval for gilteritinib
Measured: Cycle 1 (Each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2023
- Study start22 Feb 2024
- Primary completionDec 2026 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AMLStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 171 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kura Oncology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06001788
- Sponsor's protocol ID
- KO-MEN-008
- Status last verified
- Aug 2026
- First submitted
- 7 Aug 2023
- Last updated
- 20 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
- Expanded access
- Available