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

Purpose

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
  • NPM1 Mutation
  • KMT2Ar
  • Myeloid Sarcoma
  • Nucleophosmin 1-mutated Acute Myeloid Leukemia

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • 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

Exclusion Criteria

  • 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 - 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

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Dose Escalation: Ziftomenib with Venetoclax and Azacitidine in R/R NPM1-m (A-1) 		Ziftomenib with Venetoclax and Azacitidine in relapsed/refractory NPM1-m AML patients who have failed at least one prior line of therapy
  • Drug: Ziftomenib
    Oral Administration
    Other names:
    • KO-539
  • Drug: Venetoclax
    Oral Administration
    Other names:
    • Venclexta
    • Venclyxto
  • Drug: Azacitidine
    Subcutaneous or Intravenous Administration
    Other names:
    • Azadine
    • Vidaza
Experimental
Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in R/R NPM1-m (A-1) 		Ziftomenib with Venetoclax and Azacitidine in relapsed/refractory NPM1-m AML patients who have failed at least one prior line of therapy
  • Drug: Ziftomenib
    Oral Administration
    Other names:
    • KO-539
  • Drug: Venetoclax
    Oral Administration
    Other names:
    • Venclexta
    • Venclyxto
  • Drug: Azacitidine
    Subcutaneous or Intravenous Administration
    Other names:
    • Azadine
    • Vidaza
Experimental
Dose Escalation: Ziftomenib with 7+3 in 1L NPM1-m/FLT3 wildtype (A-2) 		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
  • Drug: Ziftomenib
    Oral Administration
    Other names:
    • KO-539
  • Drug: Daunorubicin
    Intravenous Administration
    Other names:
    • Cerubidine
    • daunomycin
  • Drug: Cytarabine
    Intravenous Administration
    Other names:
    • cytosine arabinoside (ara-C)
    • Cytosar-U
    • Tarabine PFS
Experimental
Dose Validation/Expansion: Ziftomenib with 7+3 in 1L NPM1-m/FLT3 wildtype (A-2) 		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
  • Drug: Ziftomenib
    Oral Administration
    Other names:
    • KO-539
  • Drug: Daunorubicin
    Intravenous Administration
    Other names:
    • Cerubidine
    • daunomycin
  • Drug: Cytarabine
    Intravenous Administration
    Other names:
    • cytosine arabinoside (ara-C)
    • Cytosar-U
    • Tarabine PFS
Experimental
Dose Validation/Expansion: Ziftomenib with Venetoclax in R/R NPM1-m (A-3) 		Ziftomenib with Venetoclax in relapsed/refractory NPM1-m AML patients who have failed at least one prior line of therapy
  • Drug: Ziftomenib
    Oral Administration
    Other names:
    • KO-539
  • Drug: Venetoclax
    Oral Administration
    Other names:
    • Venclexta
    • Venclyxto
Experimental
Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in 1L NPM1-m (A-4) 		Ziftomenib with Venetoclax and Azacitidine in newly diagnosed NPM1-m AML patients
  • Drug: Ziftomenib
    Oral Administration
    Other names:
    • KO-539
  • Drug: Venetoclax
    Oral Administration
    Other names:
    • Venclexta
    • Venclyxto
  • Drug: Azacitidine
    Subcutaneous or Intravenous Administration
    Other names:
    • Azadine
    • Vidaza
Experimental
Dose Escalation: Ziftomenib with Venetoclax and Azacitidine in R/R KMT2A-r (B-1) 		Ziftomenib with Venetoclax and Azacitidine in relapsed/refractory KMT2A-r AML patients who have failed at least one prior line of therapy
  • Drug: Ziftomenib
    Oral Administration
    Other names:
    • KO-539
  • Drug: Venetoclax
    Oral Administration
    Other names:
    • Venclexta
    • Venclyxto
  • Drug: Azacitidine
    Subcutaneous or Intravenous Administration
    Other names:
    • Azadine
    • Vidaza
Experimental
Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in R/R KMT2A-r (B-1) 		Ziftomenib with Venetoclax and Azacitidine in relapsed/refractory KMT2A-r AML patients who have failed at least one prior line of therapy
  • Drug: Ziftomenib
    Oral Administration
    Other names:
    • KO-539
  • Drug: Venetoclax
    Oral Administration
    Other names:
    • Venclexta
    • Venclyxto
  • Drug: Azacitidine
    Subcutaneous or Intravenous Administration
    Other names:
    • Azadine
    • Vidaza
Experimental
Dose Escalation: Ziftomenib with 7+3 in 1L KMT2A-r (B-2) 		Ziftomenib with 7+3 in newly diagnosed KMT2A-r AML patients who are candidates for intensive chemotherapy
  • Drug: Ziftomenib
    Oral Administration
    Other names:
    • KO-539
  • Drug: Daunorubicin
    Intravenous Administration
    Other names:
    • Cerubidine
    • daunomycin
  • Drug: Cytarabine
    Intravenous Administration
    Other names:
    • cytosine arabinoside (ara-C)
    • Cytosar-U
    • Tarabine PFS
Experimental
Dose Validation/Expansion: Ziftomenib with 7+3 in 1L KMT2A-r (B-2) 		Ziftomenib with 7+3 in newly diagnosed KMT2A-r AML patients who are candidates for intensive therapy
  • Drug: Ziftomenib
    Oral Administration
    Other names:
    • KO-539
  • Drug: Daunorubicin
    Intravenous Administration
    Other names:
    • Cerubidine
    • daunomycin
  • Drug: Cytarabine
    Intravenous Administration
    Other names:
    • cytosine arabinoside (ara-C)
    • Cytosar-U
    • Tarabine PFS
Experimental
Dose Validation/Expansion: Ziftomenib with Venetoclax + Azacitidine in 1L KMT2A-r (B-3) 		Ziftomenib with Venetoclax and Azacitidine in newly diagnosed KMT2A-r AML patients
  • Drug: Ziftomenib
    Oral Administration
    Other names:
    • KO-539
  • Drug: Venetoclax
    Oral Administration
    Other names:
    • Venclexta
    • Venclyxto
  • Drug: Azacitidine
    Subcutaneous or Intravenous Administration
    Other names:
    • Azadine
    • Vidaza
Experimental
Dose Escalation: Ziftomenib with 7+3+quizartinib in 1L NPM1-m/FLT3-ITD+ AML patients (C-1) 		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
  • Drug: Ziftomenib
    Oral Administration
    Other names:
    • KO-539
  • Drug: Daunorubicin
    Intravenous Administration
    Other names:
    • Cerubidine
    • daunomycin
  • Drug: Cytarabine
    Intravenous Administration
    Other names:
    • cytosine arabinoside (ara-C)
    • Cytosar-U
    • Tarabine PFS
  • Drug: Quizartinib
    Oral Administration
    Other names:
    • Vanflyta
Experimental
Dose Validation/Expansion: Ziftomenib with 7+3+quizartinib in 1L NPM1-m/FLT3-ITD+ AML patients (C-1) 		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
  • Drug: Ziftomenib
    Oral Administration
    Other names:
    • KO-539
  • Drug: Daunorubicin
    Intravenous Administration
    Other names:
    • Cerubidine
    • daunomycin
  • Drug: Cytarabine
    Intravenous Administration
    Other names:
    • cytosine arabinoside (ara-C)
    • Cytosar-U
    • Tarabine PFS
  • Drug: Quizartinib
    Oral Administration
    Other names:
    • Vanflyta

Recruiting Locations

Mayo Clinic - Phoenix
Phoenix, Arizona 85054
Contact:
Clinical Trials Referral Office
855-776-0015

Moores UC San Diego Cancer Center
La Jolla, California 92093
Contact:
Krisma Montalvo
k1montalvo@health.ucsd.edu

USC / Norris Comprehensive Cancer Center
Los Angeles, California 90033
Contact:
Christine Duran
323-865-0371
duran_c@med.usc.edu

UCLA - Bowyer Oncology Center
Los Angeles, California 90095
Contact:
Bruck Habtemariam
310-794-0242
bhabtemariam@mednet.ucla.edu

UC Irvine Health Chao Family Comprehensive Cancer Center
Orange, California 92868
Contact:
Research Line
877-827-8839
ucstudy@hs.uci.edu

University of Colorado
Aurora, Colorado 80045

Colorado Blood Cancer Institute
Denver, Colorado 80218
Contact:
Patient Clinic
720-754-4800
PSLMDLCBCINewClinicPatient@HCAHealthcare.com

Yale Cancer Center and Smilow Cancer Hospital
New Haven, Connecticut 06510
Contact:
Farah Fasihuddin
203-737-3472
farah.fasihuddin@yale.edu

Mayo Clinic Jacksonville
Jacksonville, Florida 32224
Contact:
Clinical Trials Referral Office
855-776-0015

Emory Healthcare - The Emory Clinic
Atlanta, Georgia 30308
Contact:
Gigi Stoneback
gissela.blanco.stoneback@emory.edu

Georgia Cancer Center at Augusta University
Augusta, Georgia 30912
Contact:
Amanda Spires
amspires@augusta.edu

Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago, Illinois 60611
Contact:
312-695-9367
cancer@northwestern.edu

Loyola University Medical Center
Maywood, Illinois 60153

University of Iowa Hospitals & Clinics
Iowa City, Iowa 52242
Contact:
Cena Jones
cena-jones@uiowa.edu

The University of Kansas Medical Center Research Institute
Fairway, Kansas 66205
Contact:
Thania Medrano
913-945-7552
CTNurseNav@kumc.edu

University of Kentucky Markey Cancer Center
Louisville, Kentucky 40202
Contact:
Ashley Walton-Robbins
Ashley.Walton-Robbins@uky.edu

Norton Cancer Institute - St. Matthews
Louisville, Kentucky 40207
Contact:
502-899-3366
leukemia-NCIResearch@nortonhealthcare.org

Ochsner MD Anderson Cancer Center
Jefferson, Louisiana 70121
Contact:
Amanda Woolery, RN
504-842-0275
amanda.woolery@ochsner.org

Johns Hopkins School of Medicine
Baltimore, Maryland 21205
Contact:
I. Gojo
igojo1@jhmi.edu

Massachusetts General Hospital
Boston, Massachusetts 02114
Contact:
Christine Connelly
617-724-1124
cconnolly1@mgh.harvard.edu

UMass Chan Medical School
Worcester, Massachusetts 01655
Contact:
508-856-3216
Cancer.research@umassmed.edu

University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan 48109
Contact:
Cancer AnswerLine
800-865-1125
CancerAnswerLine@med.umich.edu

Karmanos Cancer Institute
Detroit, Michigan 48201
Contact:
Carmen Rush
800-527-6266
rushc@karmanos.org

University of Minnesota
Minneapolis, Minnesota 55455

Mayo Clinic - Rochester
Rochester, Minnesota 55905
Contact:
Clinical Trials Referral Office
855-776-0015

Hackensack University Medical Center
Hackensack, New Jersey 07601
Contact:
Oncology Clinical Research Referral Office
551-996-1777
OncologyResearchReferral@hmhn.org

Rutgers Cancer Institute
New Brunswick, New Jersey 08903
Contact:
Anita Trupiano
ar2069@cinj.rutgers.edu

Roswell Park Comprehensive Cancer Center
Buffalo, New York 14203
Contact:
877-275-7724
askrpci@roswellpark.org

New York - Presbyterian / Weill Cornell Medicine
New York, New York 10021
Contact:
Tania J Curcio
tjc9003@med.cornell.edu

Mount Sinai - Ruttenberg Treatment Center
New York, New York 10029
Contact:
Tina Czaplinska
tina.czaplinska@mssm.edu

Columbia University Medical Center
New York, New York 10032
Contact:
Research Nurse Navigator
212-342-5162
cancerclinicaltrials@cumc.columbia.edu

Stony Brook University Hospital
Stony Brook, New York 11794
Contact:
Pushpa Talanki
631-638-0815
Pushpa.Talanki@stonybrookmedicine.edu

Duke Blood Cancer Center
Durham, North Carolina 27705
Contact:
Quinna Lawson
quinna.marshburn@duke.edu

University Hospitals Cleveland Medical Center
Cleveland, Ohio 44106
Contact:
Sarah Gollwitzer
Sarah.Gollwitzer@UHhospitals.org

Cleveland Clinic Taussig Cancer Institute
Cleveland, Ohio 44195
Contact:
Cancer Answer Line
866-223-8100
ADVANIA@ccf.org

The James Cancer Hospital and Solove Research Institute
Columbus, Ohio 43210
Contact:
Hanna Cordes
Hanna.cordes@osumc.edu

OU Health Stephenson Cancer Center
Oklahoma City, Oklahoma 73104
Contact:
Cynthia Lowery
Cynthia-Lowery@ouhsc.edu

Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania 19104
Contact:
Jessica Ritter
Jessica.Ritter@pennmedicine.upenn.edu

TriStar Bone Marrow Transplant
Nashville, Tennessee 37203
Contact:
Ask Sarah
844-482-4812

Sarah Cannon Research Institute - St. David's South Austin Medical Center / Texas Oncology South Austin
Austin, Texas 78704
Contact:
Amy Hammack
amy.hammack@sarahcannon.com

UT Southwestern - Simmons Cancer Center
Dallas, Texas 75235
Contact:
Phase I Team
214-648-7097
HemeTeam@groups.utsouthwestern.edu

MD Anderson Cancer Center
Houston, Texas 77030
Contact:
Ramya Ganesh
713-792-5640
rganesh@mdanderson.org

University of Wisconsin Hospital and Clinics
Madison, Wisconsin 53792
Contact:
UW Cancer Connect
800-622-8922
clinicaltrials@cancer.wisc.edu

Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin 53226
Contact:
Medical College of WI Cancer Center Clinical Trials Office
414-805-8900
cccto@mcw.edu

More Details

NCT ID
NCT05735184
Status
Recruiting
Sponsor
Kura Oncology, Inc.

Study Contact

Kura Medical Information
844-KURAONC
medinfo@kuraoncology.com

For help using this page: trialstoday@researchmatch.org or call 855-514-7001

ResearchMatch is funded in part by the National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program, led by the NIH’s National Center for Advancing Translational Sciences (NCATS), grants UL1TR000445 and 1U54RR032646-01, and grant U24TR001579 from NCATS and the National Library of Medicine. The content of this website is solely the responsibility of ResearchMatch and Vanderbilt University and does not necessarily represent the official views of the NIH, NCATS, or NLM.

Vanderbilt University Medical Center