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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

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

The University of Kansas Medical Center Research Institute
Fairway 4271358, Kansas 4273857 66205
Contact:
Thania Medrano
913-945-7552
CTNurseNav@kumc.edu

More Details

Status
Recruiting
Sponsor
Kura Oncology, Inc.

Study Contact

Clinical Operations
617-588-3755
KO-MEN-007@kuraoncology.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.