Acute Myeloid LeukemiaPhase 1NCT05735184
A Study to Investigate the Safety and Tolerability of Ziftomenib in Combination With Venetoclax/Azacitidine, Venetoclax, 7+3, or 7+3+Quizartinib in Patients With AML
A Phase 1 study testing Ziftomenib, Venetoclax and Azacitidine in people with Acute Myeloid Leukemia and Mixed Lineage Leukemia Gene Mutation, run by Kura Oncology, Inc. at 44 sites in United States.
Trial summary
Ziftomenib is an investigational drug in development for the treatment of patients with acute myeloid leukemia (AML) with certain genetic alterations. This protocol has 3 separate arms that will investigate the benefits and risks of adding ziftomenib to standard-of-care (SOC) drug treatments in patients who have AML… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Mixed Lineage Leukemia Gene Mutation, Refractory AML
- What is being tested?
- Ziftomenib, Venetoclax and Azacitidine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 420 participants
- Where
- 44 sitesUnited States
- Study dates
- 18 Jul 2023to Apr 2030
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- Patients must have a documented NPM1 mutation or KMT2A rearrangement and have either newly diagnosed or relapsed/refractory AML
- Those intending treatment with intensive chemotherapy in Arm C should be NPM1-m and FLT3-ITD+ with an allelic ratio ≥0.05 and eligible for FLT3-targeted treatment
- 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 as well as a double barrier method 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 use a double barrier method of contraception from the time of screening through 180 days following the last dose of study intervention
- Female patients of childbearing potential who receive quizartinib in Arm C should use a highly effective method of contraception during quizartinib treatment and for 7 months after the last dose
Who cannot join
- Diagnosis of either acute promyelocytic leukemia or blast phase chronic myeloid leukemia
- Known history of BCR-ABL alteration
- Advanced malignant hepatic tumor
- 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 and/or up to 2 doses of cytarabine if used per institutional SOC for control of leukocytosis are permitted to meet this criterion
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- 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 and/or up to 2 doses of cytarabine per institutional standards to control leukocytosis, or prior treatment with all-transretinoic acid for initially suspected acute promyelocytic leukemia
- 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 QT interval corrected for heart rate by Fredericia's formula (QTcF)
- Arm A and Arm B: >480 ms on triplicate ECGs
- Arm C: >450 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
- Patients who have active GVHD requiring >0.5 mg/kg prednisone or any new or increase in immunosuppressants in the prior 2 weeks for GVHD treatment
Trial locations and contacts
44 sites in 1 country. Contact the study team or a site near you to ask about taking part.
44 sites in 1 country
United States44 sites, 44 recruiting
- Recruiting
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
Cancer AnswerLine, 800-865-1125, CancerAnswerLine@med.umich.edu
- Recruiting
Emory Healthcare - The Emory Clinic
Atlanta, Georgia, 30308
Gigi Stoneback, gissela.blanco.stoneback@emory.edu
- Recruiting
Georgia Cancer Center at Augusta University
Augusta, Georgia, 30912
Amanda Spires, amspires@augusta.edu
- Recruiting
University of Colorado
Aurora, Colorado, 80045
- Recruiting
Sarah Cannon Research Institute - St. David's South Austin Medical Center / Texas Oncology South Austin
Austin, Texas, 78704
Amy Hammack, amy.hammack@sarahcannon.com
- Recruiting
Johns Hopkins School of Medicine
Baltimore, Maryland, 21205
I. Gojo, igojo1@jhmi.edu
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Christine Connelly, 617-724-1124, cconnolly1@mgh.harvard.edu
- Recruiting
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14203
877-275-7724, askrpci@roswellpark.org
- Recruiting
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago, Illinois, 60611
312-695-9367, cancer@northwestern.edu
- Recruiting
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Sarah Gollwitzer, Sarah.Gollwitzer@UHhospitals.org
- Recruiting
Cleveland Clinic Taussig Cancer Institute
Cleveland, Ohio, 44195
Cancer Answer Line, 866-223-8100, ADVANIA@ccf.org
- Recruiting
The James Cancer Hospital and Solove Research Institute
Columbus, Ohio, 43210
Hanna Cordes, Hanna.cordes@osumc.edu
- Recruiting
UT Southwestern - Simmons Cancer Center
Dallas, Texas, 75235
Phase I Team, 214-648-7097, HemeTeam@groups.utsouthwestern.edu
- Recruiting
Colorado Blood Cancer Institute
Denver, Colorado, 80218
Patient Clinic, 720-754-4800, PSLMDLCBCINewClinicPatient@HCAHealthcare.com
- Recruiting
Karmanos Cancer Institute
Detroit, Michigan, 48201
Carmen Rush, 800-527-6266, rushc@karmanos.org
- Recruiting
Duke Blood Cancer Center
Durham, North Carolina, 27705
Quinna Lawson, quinna.marshburn@duke.edu
- Recruiting
The University of Kansas Medical Center Research Institute
Fairway, Kansas, 66205
Thania Medrano, 913-945-7552, CTNurseNav@kumc.edu
- Recruiting
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Oncology Clinical Research Referral Office, 551-996-1777, OncologyResearchReferral@hmhn.org
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Ramya Ganesh, 713-792-5640, rganesh@mdanderson.org
- Recruiting
University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242
Cena Jones, cena-jones@uiowa.edu
- Recruiting
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224
Clinical Trials Referral Office, 855-776-0015
- Recruiting
Ochsner MD Anderson Cancer Center
Jefferson, Louisiana, 70121
Amanda Woolery, RN, 504-842-0275, amanda.woolery@ochsner.org
- Recruiting
Moores UC San Diego Cancer Center
La Jolla, California, 92093
Krisma Montalvo, k1montalvo@health.ucsd.edu
- Recruiting
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Christine Duran, 323-865-0371, duran_c@med.usc.edu
- Recruiting
UCLA - Bowyer Oncology Center
Los Angeles, California, 90095
Bruck Habtemariam, 310-794-0242, bhabtemariam@mednet.ucla.edu
- Recruiting
University of Kentucky Markey Cancer Center
Louisville, Kentucky, 40202
Ashley Walton-Robbins, Ashley.Walton-Robbins@uky.edu
- Recruiting
Norton Cancer Institute - St. Matthews
Louisville, Kentucky, 40207
502-899-3366, leukemia-NCIResearch@nortonhealthcare.org
- Recruiting
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792
UW Cancer Connect, 800-622-8922, clinicaltrials@cancer.wisc.edu
- Recruiting
Loyola University Medical Center
Maywood, Illinois, 60153
- Recruiting
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, 53226
Medical College of WI Cancer Center Clinical Trials Office, 414-805-8900, cccto@mcw.edu
- Recruiting
University of Minnesota
Minneapolis, Minnesota, 55455
- Recruiting
TriStar Bone Marrow Transplant
Nashville, Tennessee, 37203
Ask Sarah, 844-482-4812
- Recruiting
Rutgers Cancer Institute
New Brunswick, New Jersey, 08903
Anita Trupiano, ar2069@cinj.rutgers.edu
- Recruiting
Yale Cancer Center and Smilow Cancer Hospital
New Haven, Connecticut, 06510
Farah Fasihuddin, 203-737-3472, farah.fasihuddin@yale.edu
- Recruiting
New York - Presbyterian / Weill Cornell Medicine
New York, New York, 10021
Tania J Curcio, tjc9003@med.cornell.edu
- Recruiting
Mount Sinai - Ruttenberg Treatment Center
New York, New York, 10029
Tina Czaplinska, tina.czaplinska@mssm.edu
- Recruiting
Columbia University Medical Center
New York, New York, 10032
Research Nurse Navigator, 212-342-5162, cancerclinicaltrials@cumc.columbia.edu
- Recruiting
OU Health Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Cynthia Lowery, Cynthia-Lowery@ouhsc.edu
- Recruiting
UC Irvine Health Chao Family Comprehensive Cancer Center
Orange, California, 92868
Research Line, 877-827-8839, ucstudy@hs.uci.edu
- Recruiting
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Jessica Ritter, Jessica.Ritter@pennmedicine.upenn.edu
Camilla Ludlow, camila.ludlow@pennmedicine.upenn.edu
- Recruiting
Mayo Clinic - Phoenix
Phoenix, Arizona, 85054
Clinical Trials Referral Office, 855-776-0015
- Recruiting
Mayo Clinic - Rochester
Rochester, Minnesota, 55905
Clinical Trials Referral Office, 855-776-0015
- Recruiting
Stony Brook University Hospital
Stony Brook, New York, 11794
Pushpa Talanki, 631-638-0815, Pushpa.Talanki@stonybrookmedicine.edu
- Recruiting
UMass Chan Medical School
Worcester, Massachusetts, 01655
508-856-3216, Cancer.research@umassmed.edu
About this study
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
Ziftomenib is an investigational drug in development for the treatment of patients with acute myeloid leukemia (AML) with certain genetic alterations.
This protocol has 3 separate arms that will investigate the benefits and risks of adding ziftomenib to standard-of-care (SOC) drug treatments in patients who have AML with certain genetic mutations. Both newly diagnosed and relapsed refractory patients with AML will be assigned to different cohorts based on specific study criteria and physician discretion.
The purpose of this study is to assess the safety, tolerability, and early signs of efficacy of ziftomenib in combination with SOC drugs to treat AML.
- Conditions
- Acute Myeloid Leukemia, Mixed Lineage Leukemia Gene Mutation, Refractory AML, AML With Mutated NPM1, Acute Myeloid Leukemia Recurrent, Acute Myeloid Leukemia, in Relapse
- Being tested
- Ziftomenib, Venetoclax, Azacitidine, Daunorubicin, Cytarabine
- Keywords
- Leukemia, Myeloid, AML, Hematological malignancy, KMT2A, NPM1, Menin, Acute Leukemia, Newly diagnosed AML, Untreated AML, venetoclax, cytarabine, daunorubicin, KMT2A-r, NPM1 mutation, Refractory AML, Acute Myeloid Leukemia, in Relapse, quizartinib
- Medical subject headings
- Leukemia, Myeloid, Acute, Sarcoma, Myeloid, Leukemia, Hematologic Neoplasms
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
VenetoclaxDrug
Also called Venclexta, Venclyxto
Oral Administration
AzacitidineDrug
Also called Azadine, Vidaza
Subcutaneous or Intravenous Administration
DaunorubicinDrug
Also called Cerubidine, daunomycin
Intravenous Administration
CytarabineDrug
Also called cytosine arabinoside (ara-C), Cytosar-U, Tarabine PFS
Intravenous Administration
QuizartinibDrug
Also called Vanflyta
Oral Administration
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation: Ziftomenib with Venetoclax and Azacitidine in R/R NPM1-m (A-1) | Experimental | Ziftomenib with Venetoclax and Azacitidine in relapsed/refractory NPM1-m AML patients who have failed at least one prior line of therapy Receives: Drug: Ziftomenib; Drug: Venetoclax; Drug: Azacitidine |
| Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in R/R NPM1-m (A-1) | Experimental | Ziftomenib with Venetoclax and Azacitidine in relapsed/refractory NPM1-m AML patients who have failed at least one prior line of therapy Receives: Drug: Ziftomenib; Drug: Venetoclax; Drug: Azacitidine |
| Dose Escalation: Ziftomenib with 7+3 in 1L NPM1-m/FLT3 wildtype (A-2) | Experimental | Ziftomenib with 7+3 in newly diagnosed NPM1-m AML patients who are candidates for intensive chemotherapy and must be FLT3 wildtype or ITD ratio <0.05 Receives: Drug: Ziftomenib; Drug: Daunorubicin; Drug: Cytarabine |
| Dose Validation/Expansion: Ziftomenib with 7+3 in 1L NPM1-m/FLT3 wildtype (A-2) | Experimental | Ziftomenib with 7+3 in newly diagnosed NPM1-m AML patients who are candidates for intensive chemotherapy and must be FLT3 wildtype or ITD ratio <0.05 Receives: Drug: Ziftomenib; Drug: Daunorubicin; Drug: Cytarabine |
| Dose Validation/Expansion: Ziftomenib with Venetoclax in R/R NPM1-m (A-3) | Experimental | Ziftomenib with Venetoclax in relapsed/refractory NPM1-m AML patients who have failed at least one prior line of therapy Receives: Drug: Ziftomenib; Drug: Venetoclax |
| Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in 1L NPM1-m (A-4) | Experimental | Ziftomenib with Venetoclax and Azacitidine in newly diagnosed NPM1-m AML patients Receives: Drug: Ziftomenib; Drug: Venetoclax; Drug: Azacitidine |
| Dose Escalation: Ziftomenib with Venetoclax and Azacitidine in R/R KMT2A-r (B-1) | Experimental | Ziftomenib with Venetoclax and Azacitidine in relapsed/refractory KMT2A-r AML patients who have failed at least one prior line of therapy Receives: Drug: Ziftomenib; Drug: Venetoclax; Drug: Azacitidine |
| Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in R/R KMT2A-r (B-1) | Experimental | Ziftomenib with Venetoclax and Azacitidine in relapsed/refractory KMT2A-r AML patients who have failed at least one prior line of therapy Receives: Drug: Ziftomenib; Drug: Venetoclax; Drug: Azacitidine |
| Dose Escalation: Ziftomenib with 7+3 in 1L KMT2A-r (B-2) | Experimental | Ziftomenib with 7+3 in newly diagnosed KMT2A-r AML patients who are candidates for intensive chemotherapy Receives: Drug: Ziftomenib; Drug: Daunorubicin; Drug: Cytarabine |
| Dose Validation/Expansion: Ziftomenib with 7+3 in 1L KMT2A-r (B-2) | Experimental | Ziftomenib with 7+3 in newly diagnosed KMT2A-r AML patients who are candidates for intensive therapy Receives: Drug: Ziftomenib; Drug: Daunorubicin; Drug: Cytarabine |
| Dose Validation/Expansion: Ziftomenib with Venetoclax + Azacitidine in 1L KMT2A-r (B-3) | Experimental | Ziftomenib with Venetoclax and Azacitidine in newly diagnosed KMT2A-r AML patients Receives: Drug: Ziftomenib; Drug: Venetoclax; Drug: Azacitidine |
| Dose Escalation: Ziftomenib with 7+3+quizartinib in 1L NPM1-m/FLT3-ITD+ AML patients (C-1) | Experimental | Ziftomenib with 7+3 and quizartinib in newly diagnosed NPM1-m and FLT3-ITD+ (with allelic ratio ≥0.05) AML patients who are candidates for IC and eligible to receive FLT3-targeted therapy Receives: Drug: Ziftomenib; Drug: Daunorubicin; Drug: Cytarabine; Drug: Quizartinib |
| Dose Validation/Expansion: Ziftomenib with 7+3+quizartinib in 1L NPM1-m/FLT3-ITD+ AML patients (C-1) | Experimental | Ziftomenib with 7+3 and quizartinib in newly diagnosed NPM1-m and FLT3-ITD+ (with allelic ratio ≥0.05) AML patients who are candidates for IC and eligible to receive FLT3-targeted therapy Receives: Drug: Ziftomenib; Drug: Daunorubicin; Drug: Cytarabine; Drug: Quizartinib |
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 (Part 1a only)
Assessed by the NCI-CTCAE v5.0
Measured: During the first 28 days of ziftomenib in combination with SOC backbone treatment (1 cycle)
Descriptive statistics of adverse events
Assessed by the NCI-CTCAE v5.0
Measured: From Cycle 1 Day 1 up to and including 28 days following the end of 36 months of treatment
Complete remission (CR) rate
Assessed by the ELN 2022 criteria
Measured: Until relapse, new anti-cancer therapy, death, or up to 36 months of treatment, whichever occurs first
Secondary outcomes (23)
Composite Complete Remission (CRc)
Assessed by the ELN 2022 criteria
Measured: Until relapse, new anti-cancer therapy, death, or up to 36 months of treatment, whichever occurs first
Morphologic leukemia-free state (MLFS) rate
Assessed by the ELN 2022 criteria
Measured: Until relapse, new anti-cancer therapy, death, or up to 36 months of treatment, whichever comes first
Measurable residual disease (MRD)
Assessed by multiparameter flow cytometry (MFC) and/or molecular analysis (NGS, PCR)
Measured: Until relapse, new anti-cancer therapy, death, or up to 36 months of treatment, whichever occurs first
Median OS
To assess overall survival of ziftomenib
Measured: From Cycle 1 Day 1 to date of death from any cause, assessed up to 36 months of treatment
Proportion of patients alive
To assess proportion of patients alive at 1 year following start of treatment with ziftomenib
Measured: From Cycle 1 Day 1 until death from any cause, assessed up to 1 year following start of treatment
Median EFS
To assess median event free survival
Measured: From Cycle 1 Day 1 to treatment failure, hematologic relapse following CR, or death from any cause, whichever comes first, assessed up to 36 months of treatment
EFS
To assess event free survival at 1 year
Measured: From Cycle 1 Day 1 to treatment failure, hematologic relapse following CR, or death from any cause, whichever comes first, assessed up to 1 year following start of treatment
Median DOR
To assess median duration of remission
Measured: From time of first remission to relapse or death, whichever occurs first, assessed up to 36 months from start of treatment
Proportion of patients who undergo HSCT
To assess proportion of patients who undergo hematopoietic stem cell transplant
Measured: From Cycle 1 Day 1 until date of HSCT, assessed up to 36 months of treatment
TI
To assess rate of transfusion independence
Measured: From 28 days prior to Cycle 1 Day 1 up to and including 28 days following the end of 36 months of treatment
Cmax
Maximum plasma concentration (Cmax) of ziftomenib and metabolites
Measured: Cycle 1; each cycle is 28 days
Tmax
Time to maximum plasma concentration (Tmax) of ziftomenib and metabolites
Measured: Cycle 1; each cycle is 28 days
AUC0-last
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
Measured: Cycle 1; each cycle is 28 days
AUCtau
Area under the concentration-time curve over a dosing interval (AUCtau) of ziftomenib
Measured: Cycle 1; each cycle is 28 days
Accumulation ratio of ziftomenib and metabolites
To assess accumulation ratio of ziftomenib and metabolites
Measured: Cycle 1; each cycle is 28 days
Cmax of venetoclax
Maximum plasma concentration (Cmax) of venetoclax
Measured: Cycle 1; each cycle is 28 days
Tmax of venetoclax
Time to maximum plasma concentration (Tmax) of venetoclax
Measured: Cycle 1; each cycle is 28 days
AUC0-last of venetoclax
Area under the concentration-time curve from time zero to the time of the last quantifiable concentration after dosing (AUC0-last) of venetoclax
Measured: Cycle 1; each cycle is 28 days
AUCtau of venetoclax
Area under the concentration-time curve over a dosing interval (AUCtau) of venetoclax
Measured: Cycle 1; each cycle is 28 days
Cmax of quizartinib
Maximum plasma concentration (Cmax) of quizartinib
Measured: Cycle 1; each cycle is 28 days
Tmax of quizartinib
Time to maximum plasma concentration (Tmax) of quizartinib
Measured: Cycle 1; each cycle is 28 days
AUC0-last of quizartinib
Area under the concentration-time curve from time zero to the time of the last quantifiable concentration after dosing (AUC0-last) of quizartinib
Measured: Cycle 1; each cycle is 28 days
AUCtau of quizartinib
Area under the concentration-time curve over a dosing interval (AUCtau) of quizartinib
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 Feb 2023
- Study start18 Jul 2023
- Primary completionApr 2030 (estimated)
- Study completionApr 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies 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
- 420 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
- NCT05735184
- Sponsor's protocol ID
- KO-MEN-007
- Status last verified
- Mar 2026
- First submitted
- 9 Feb 2023
- Last updated
- 13 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
- Expanded access
- Available
Publications
Wang ES, Erba HP, Zeidan AM, Roboz GJ, Altman JK, Advani AS, Lin TL, Strickland SA, Juckett MB, Pratz KW, Mangan JK, McMahon CM, Alsfeld LC, Balasubramanian SK, Guru Murthy GS, Rotta M, Palmisiano N, McCloskey J, Saliba AN, Khawandanah M, Madanat YF, Naqvi K, Qasrawi AH, Schiller GJ, Badar T, Gojo I, Yaghmour G, Osman D, Zhang H, Tian Y, Soifer HS, Riches M, Corum D, Leoni M, Fathi AT, Issa GC. Ziftomenib with venetoclax and azacitidine in relapsed/refractory NPM1-mutated acute myeloid leukemia. Blood. 2026 Jun 2:blood.2026034043. doi: 10.1182/blood.2026034043. Online ahead of print.
PubMed 42227701
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05735184
- Acronym / sponsor ID
- KO-MEN-007
- Conditions
- Acute Myeloid Leukemia, Mixed Lineage Leukemia Gene Mutation, Refractory AML, AML With Mutated NPM1, Acute Myeloid Leukemia Recurrent, Acute Myeloid Leukemia, in Relapse
- Keywords
- Leukemia, Myeloid, AML, Hematological malignancy, KMT2A, NPM1, Menin, Acute Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 420 participants (estimated)
- Lead sponsor
- Kura Oncology, Inc.Industry (pharma, biotech, devices)
- Study start
- 18 Jul 2023 (actual)
- Primary completion
- Apr 2030 (estimated)
- Study completion
- Apr 2030 (estimated)
- First posted
- 21 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ziftomenib is an investigational drug in development for the treatment of patients with acute myeloid leukemia (AML) with certain genetic alterations.
This protocol has 3 separate arms that will investigate the benefits and risks of adding ziftomenib to standard-of-care (SOC) drug treatments in patients who have AML with certain genetic mutations. Both newly diagnosed and relapsed refractory patients with AML will be assigned to different cohorts based on specific study criteria and physician discretion.
The purpose of this study is to assess the safety, tolerability, and early signs of efficacy of ziftomenib in combination with SOC drugs to treat AML.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 13
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation: Ziftomenib with Venetoclax and Azacitidine in R/R NPM1-m (A-1) | Experimental | Drug: Ziftomenib, Drug: Venetoclax, Drug: AzacitidineZiftomenib with Venetoclax and Azacitidine in relapsed/refractory NPM1-m AML patients who have failed at least one prior line of therapy |
| Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in R/R NPM1-m (A-1) | Experimental | Drug: Ziftomenib, Drug: Venetoclax, Drug: AzacitidineZiftomenib with Venetoclax and Azacitidine in relapsed/refractory NPM1-m AML patients who have failed at least one prior line of therapy |
| Dose Escalation: Ziftomenib with 7+3 in 1L NPM1-m/FLT3 wildtype (A-2) | Experimental | Drug: Ziftomenib, Drug: Daunorubicin, Drug: CytarabineZiftomenib with 7+3 in newly diagnosed NPM1-m AML patients who are candidates for intensive chemotherapy and must be FLT3 wildtype or ITD ratio <0.05 |
| Dose Validation/Expansion: Ziftomenib with 7+3 in 1L NPM1-m/FLT3 wildtype (A-2) | Experimental | Drug: Ziftomenib, Drug: Daunorubicin, Drug: CytarabineZiftomenib with 7+3 in newly diagnosed NPM1-m AML patients who are candidates for intensive chemotherapy and must be FLT3 wildtype or ITD ratio <0.05 |
| Dose Validation/Expansion: Ziftomenib with Venetoclax in R/R NPM1-m (A-3) | Experimental | Drug: Ziftomenib, Drug: VenetoclaxZiftomenib with Venetoclax in relapsed/refractory NPM1-m AML patients who have failed at least one prior line of therapy |
| Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in 1L NPM1-m (A-4) | Experimental | Drug: Ziftomenib, Drug: Venetoclax, Drug: AzacitidineZiftomenib with Venetoclax and Azacitidine in newly diagnosed NPM1-m AML patients |
| Dose Escalation: Ziftomenib with Venetoclax and Azacitidine in R/R KMT2A-r (B-1) | Experimental | Drug: Ziftomenib, Drug: Venetoclax, Drug: AzacitidineZiftomenib with Venetoclax and Azacitidine in relapsed/refractory KMT2A-r AML patients who have failed at least one prior line of therapy |
| Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in R/R KMT2A-r (B-1) | Experimental | Drug: Ziftomenib, Drug: Venetoclax, Drug: AzacitidineZiftomenib with Venetoclax and Azacitidine in relapsed/refractory KMT2A-r AML patients who have failed at least one prior line of therapy |
| Dose Escalation: Ziftomenib with 7+3 in 1L KMT2A-r (B-2) | Experimental | Drug: Ziftomenib, Drug: Daunorubicin, Drug: CytarabineZiftomenib with 7+3 in newly diagnosed KMT2A-r AML patients who are candidates for intensive chemotherapy |
| Dose Validation/Expansion: Ziftomenib with 7+3 in 1L KMT2A-r (B-2) | Experimental | Drug: Ziftomenib, Drug: Daunorubicin, Drug: CytarabineZiftomenib with 7+3 in newly diagnosed KMT2A-r AML patients who are candidates for intensive therapy |
| Dose Validation/Expansion: Ziftomenib with Venetoclax + Azacitidine in 1L KMT2A-r (B-3) | Experimental | Drug: Ziftomenib, Drug: Venetoclax, Drug: AzacitidineZiftomenib with Venetoclax and Azacitidine in newly diagnosed KMT2A-r AML patients |
| Dose Escalation: Ziftomenib with 7+3+quizartinib in 1L NPM1-m/FLT3-ITD+ AML patients (C-1) | Experimental | Drug: Ziftomenib, Drug: Daunorubicin, Drug: Cytarabine, Drug: QuizartinibZiftomenib with 7+3 and quizartinib in newly diagnosed NPM1-m and FLT3-ITD+ (with allelic ratio ≥0.05) AML patients who are candidates for IC and eligible to receive FLT3-targeted therapy |
| Dose Validation/Expansion: Ziftomenib with 7+3+quizartinib in 1L NPM1-m/FLT3-ITD+ AML patients (C-1) | Experimental | Drug: Ziftomenib, Drug: Daunorubicin, Drug: Cytarabine, Drug: QuizartinibZiftomenib with 7+3 and quizartinib in newly diagnosed NPM1-m and FLT3-ITD+ (with allelic ratio ≥0.05) AML patients who are candidates for IC and eligible to receive FLT3-targeted therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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 as well as a double barrier method 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 use a double barrier method of contraception from the time of screening through 180 days following the last dose of study intervention
Key exclusion criteria (18 listed)
- Diagnosis of either acute promyelocytic leukemia or blast phase chronic myeloid leukemia
- Known history of BCR-ABL alteration
- Advanced malignant hepatic tumor
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZiftomenibAlso: KO-539Oral Administration | Drug | Dose Escalation: Ziftomenib with 7+3 in 1L KMT2A-r (B-2), Dose Escalation: Ziftomenib with 7+3 in 1L NPM1-m/FLT3 wildtype (A-2), Dose Escalation: Ziftomenib with 7+3+quizartinib in 1L NPM1-m/FLT3-ITD+ AML patients (C-1), Dose Escalation: Ziftomenib with Venetoclax and Azacitidine in R/R KMT2A-r (B-1), Dose Escalation: Ziftomenib with Venetoclax and Azacitidine in R/R NPM1-m (A-1), Dose Validation/Expansion: Ziftomenib with 7+3 in 1L KMT2A-r (B-2), Dose Validation/Expansion: Ziftomenib with 7+3 in 1L NPM1-m/FLT3 wildtype (A-2), Dose Validation/Expansion: Ziftomenib with 7+3+quizartinib in 1L NPM1-m/FLT3-ITD+ AML patients (C-1), Dose Validation/Expansion: Ziftomenib with Venetoclax + Azacitidine in 1L KMT2A-r (B-3), Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in 1L NPM1-m (A-4), Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in R/R KMT2A-r (B-1), Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in R/R NPM1-m (A-1), Dose Validation/Expansion: Ziftomenib with Venetoclax in R/R NPM1-m (A-3) |
| VenetoclaxAlso: Venclexta, VenclyxtoOral Administration | Drug | Dose Escalation: Ziftomenib with Venetoclax and Azacitidine in R/R KMT2A-r (B-1), Dose Escalation: Ziftomenib with Venetoclax and Azacitidine in R/R NPM1-m (A-1), Dose Validation/Expansion: Ziftomenib with Venetoclax + Azacitidine in 1L KMT2A-r (B-3), Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in 1L NPM1-m (A-4), Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in R/R KMT2A-r (B-1), Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in R/R NPM1-m (A-1), Dose Validation/Expansion: Ziftomenib with Venetoclax in R/R NPM1-m (A-3) |
| AzacitidineAlso: Azadine, VidazaSubcutaneous or Intravenous Administration | Drug | Dose Escalation: Ziftomenib with Venetoclax and Azacitidine in R/R KMT2A-r (B-1), Dose Escalation: Ziftomenib with Venetoclax and Azacitidine in R/R NPM1-m (A-1), Dose Validation/Expansion: Ziftomenib with Venetoclax + Azacitidine in 1L KMT2A-r (B-3), Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in 1L NPM1-m (A-4), Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in R/R KMT2A-r (B-1), Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in R/R NPM1-m (A-1) |
| DaunorubicinAlso: Cerubidine, daunomycinIntravenous Administration | Drug | Dose Escalation: Ziftomenib with 7+3 in 1L KMT2A-r (B-2), Dose Escalation: Ziftomenib with 7+3 in 1L NPM1-m/FLT3 wildtype (A-2), Dose Escalation: Ziftomenib with 7+3+quizartinib in 1L NPM1-m/FLT3-ITD+ AML patients (C-1), Dose Validation/Expansion: Ziftomenib with 7+3 in 1L KMT2A-r (B-2), Dose Validation/Expansion: Ziftomenib with 7+3 in 1L NPM1-m/FLT3 wildtype (A-2), Dose Validation/Expansion: Ziftomenib with 7+3+quizartinib in 1L NPM1-m/FLT3-ITD+ AML patients (C-1) |
| CytarabineAlso: cytosine arabinoside (ara-C), Cytosar-U, Tarabine PFSIntravenous Administration | Drug | Dose Escalation: Ziftomenib with 7+3 in 1L KMT2A-r (B-2), Dose Escalation: Ziftomenib with 7+3 in 1L NPM1-m/FLT3 wildtype (A-2), Dose Escalation: Ziftomenib with 7+3+quizartinib in 1L NPM1-m/FLT3-ITD+ AML patients (C-1), Dose Validation/Expansion: Ziftomenib with 7+3 in 1L KMT2A-r (B-2), Dose Validation/Expansion: Ziftomenib with 7+3 in 1L NPM1-m/FLT3 wildtype (A-2), Dose Validation/Expansion: Ziftomenib with 7+3+quizartinib in 1L NPM1-m/FLT3-ITD+ AML patients (C-1) |
| QuizartinibAlso: VanflytaOral Administration | Drug | Dose Escalation: Ziftomenib with 7+3+quizartinib in 1L NPM1-m/FLT3-ITD+ AML patients (C-1), Dose Validation/Expansion: Ziftomenib with 7+3+quizartinib in 1L NPM1-m/FLT3-ITD+ AML patients (C-1) |
Primary outcome
Rate of dose limiting toxicities (DLTs) per dose level (Part 1a only)
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: From Cycle 1 Day 1 up to and including 28 days following the end of 36 months of treatment
Assessed by the NCI-CTCAE v5.0
Complete remission (CR) rate
Time frame: Until relapse, new anti-cancer therapy, death, or up to 36 months of treatment, whichever occurs first
Assessed by the ELN 2022 criteria
23 secondary outcomes
Composite Complete Remission (CRc)
Time frame: Until relapse, new anti-cancer therapy, death, or up to 36 months of treatment, whichever occurs first
Morphologic leukemia-free state (MLFS) rate
Time frame: Until relapse, new anti-cancer therapy, death, or up to 36 months of treatment, whichever comes first
Measurable residual disease (MRD)
Time frame: Until relapse, new anti-cancer therapy, death, or up to 36 months of treatment, whichever occurs first
Median OS
Time frame: From Cycle 1 Day 1 to date of death from any cause, assessed up to 36 months of treatment
Proportion of patients alive
Time frame: From Cycle 1 Day 1 until death from any cause, assessed up to 1 year following start of treatment
Median EFS
Time frame: From Cycle 1 Day 1 to treatment failure, hematologic relapse following CR, or death from any cause, whichever comes first, assessed up to 36 months of treatment
EFS
Time frame: From Cycle 1 Day 1 to treatment failure, hematologic relapse following CR, or death from any cause, whichever comes first, assessed up to 1 year following start of treatment
Median DOR
Time frame: From time of first remission to relapse or death, whichever occurs first, assessed up to 36 months from start of treatment
Proportion of patients who undergo HSCT
Time frame: From Cycle 1 Day 1 until date of HSCT, assessed up to 36 months of treatment
TI
Time frame: From 28 days prior to Cycle 1 Day 1 up to and including 28 days following the end of 36 months of treatment
Cmax
Time frame: Cycle 1; each cycle is 28 days
Tmax
Time frame: Cycle 1; each cycle is 28 days
AUC0-last
Time frame: Cycle 1; each cycle is 28 days
AUCtau
Time frame: Cycle 1; each cycle is 28 days
Accumulation ratio of ziftomenib and metabolites
Time frame: Cycle 1; each cycle is 28 days
Cmax of venetoclax
Time frame: Cycle 1; each cycle is 28 days
Tmax of venetoclax
Time frame: Cycle 1; each cycle is 28 days
AUC0-last of venetoclax
Time frame: Cycle 1; each cycle is 28 days
AUCtau of venetoclax
Time frame: Cycle 1; each cycle is 28 days
Cmax of quizartinib
Time frame: Cycle 1; each cycle is 28 days
Tmax of quizartinib
Time frame: Cycle 1; each cycle is 28 days
AUC0-last of quizartinib
Time frame: Cycle 1; each cycle is 28 days
AUCtau of quizartinib
Time frame: Cycle 1; each cycle is 28 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2026.
- Derived from this study: PubMed 42227701Wang ES, Erba HP, Zeidan AM, Roboz GJ, Altman JK, Advani AS, Lin TL, Strickland SA, Juckett MB, Pratz KW, Mangan JK, McMahon CM, Alsfeld LC, Balasubramanian SK, Guru Murthy GS, Rotta M, Palmisiano N, McCloskey J, Saliba AN, Khawandanah M, Madanat YF, Naqvi K, Qasrawi AH, Schiller GJ, Badar T, Gojo I, Yaghmour G, Osman D, Zhang H, Tian Y, Soifer HS, Riches M, Corum D, Leoni M, Fathi AT, Issa GC. Ziftomenib with venetoclax and azacitidine in relapsed/refractory NPM1-mutated acute myeloid leukemia. Blood. 2026 Jun 2:blood.2026034043. doi: 10.1182/blood.2026034043. Online ahead of print.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
44 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ziftomenib, Venetoclax and Azacitidine in people with Acute Myeloid Leukemia and Mixed Lineage Leukemia Gene Mutation, run by Kura Oncology, Inc. at 44 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 44 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kura Medical Information (844-KURAONC ext. (844-587-2662), medinfo@kuraoncology.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of dose limiting toxicities (DLTs) per dose level (Part 1a only) (time frame: During the first 28 days of ziftomenib in combination with SOC backbone treatment (1 cycle)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05735184, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2026.