Investigating Ziftomenib with Other Treatments for Acute Myeloid Leukemia

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This Phase 1 study aims to evaluate the safety and tolerability of ziftomenib when combined with venetoclax and azacitidine, venetoclax alone, or the 7+3 regimen in patients with acute myeloid leukemia (AML) who have specific genetic mutations. The study will focus on two molecularly-defined groups: those with NPM1 mutations and those with KMT2A rearrangements. Participants will be monitored for preliminary antileukemic activity and overall safety of the treatment combinations. The study is designed for patients who are newly diagnosed or have relapsed/refractory AML.

Why it matters

Who can join: the full rules

Key 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

Key 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

Where it's running

• Mayo Clinic - Phoenix
  Phoenix, Arizona, United States Recruiting
• Moores UC San Diego Cancer Center
  La Jolla, California, United States Recruiting
• USC / Norris Comprehensive Cancer Center
  Los Angeles, California, United States Recruiting
• UCLA - Bowyer Oncology Center
  Los Angeles, California, United States Recruiting
• UC Irvine Health Chao Family Comprehensive Cancer Center
  Orange, California, United States Recruiting
• University of Colorado
  Aurora, Colorado, United States Recruiting

Study contacts

• Study coordinator: Kura Medical Information
• Email: medinfo@kuraoncology.com
• Phone: 844-KURAONC

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Examining the safety of ziftomenib combinations for patients with relapsed acute myeloid leukemia

  This study is testing if combining ziftomenib with standard treatments can safely help people with relapsed acute myeloid leukemia feel better and improve their chances of recovery.

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• Personalized T-cell therapy with a DC/AML fusion vaccine plus decitabine and venetoclax for AML

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• APL-like A Cute Myeloid Leukemia in NPM1-M mutated patients: distinctive features and early vascular events

  This observational study tests whether an APL-like appearance in NPM1-mutated AML can predict early clotting problems and vascular events.

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• VAM (liposomal mitoxantrone) for secondary AML and myeloid sarcoma

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• Quizartinib maintenance at two doses for FLT3‑ITD positive AML in first complete remission

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  Recruiting at 50 sites Phase 2 Daiichi Sankyo · Birmingham, Alabama and 63 other locations · NCT06824168

• Ziftomenib plus quizartinib dose-finding for relapsed/refractory AML with NPM1, KMT2A, or NUP98 alterations

  This trial tests an all-oral combination of ziftomenib and quizartinib in adults with relapsed or refractory AML that has NPM1 mutations, KMT2A rearrangements, or NUP98 rearrangements.

  Recruiting Phase 1 M.D. Anderson Cancer Center · Houston, Texas · NCT06769490

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.