RightFit
RecruitingPhase 1

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

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests adding ziftomenib, an experimental drug, to standard treatments for acute myeloid leukemia (AML), a blood cancer. It checks safety, side effects, and early signs that treatment works. It is for people with certain gene changes whose AML is newly diagnosed, has come back, or has not responded to treatment.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Have AML with a confirmed NPM1 gene change or KMT2A gene rearrangement.
  • For intensive chemotherapy in Arm C: have NPM1 and FLT3-ITD gene changes, a FLT3-ITD test ratio of at least 0.05, and qualify for treatment targeting FLT3.
  • Have an ECOG activity score of 0, 1, or 2: be able to care for yourself and be out of bed or a chair for more than half of waking hours.
  • Have liver, kidney, and heart function that meets the study rules.
  • If able to become pregnant, agree to the required birth control, including two barrier methods, from screening until 180 days after the last study dose.
  • If male and able to father a child, agree to avoid sex or use two barrier birth control methods from screening until 180 days after the last study dose.
  • If able to become pregnant and taking quizartinib in Arm C, use highly effective birth control during treatment and for 7 months after the last dose.

Who can't join

  • Have acute promyelocytic leukemia, blast-phase chronic myeloid leukemia, a history of a BCR-ABL gene change, or AML in the brain or spinal cord.
  • Have an advanced cancerous liver tumor, or another active cancer that is being treated with chemotherapy, is not controlled, or is getting worse.
  • Have signs that leukemia cells are blocking blood flow, or a white blood cell count above 25,000 per microliter. Certain treatments to lower the count are allowed.
  • Still have more than mild side effects from past treatment that do not affect blood cells, except hair loss.
  • Have had prior leukemia chemotherapy if newly diagnosed, except certain allowed treatments. If AML returned or resisted treatment, recent cancer or experimental treatment may exclude you under the study's timing rules.
  • Have an uncontrolled illness or infection; active HIV, hepatitis B, or hepatitis C; or a heart rhythm test result called QTcF above 480 milliseconds in Arms A or B, or above 450 milliseconds in Arm C.
  • Are pregnant or breastfeeding, or received a live, weakened vaccine within 14 days before treatment, during treatment, or afterward before B cells, a type of immune cell, recover.
  • Have active graft-versus-host disease, where donor cells attack your body, requiring more than 0.5 mg/kg of prednisone, or new or increased immune-suppressing medicine for it in the past 2 weeks.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

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

Study sites (44)

AZ

CA

CO

CT

FL

GA

IA

IL

KS

KY

LA

MA

MD

MI

MN

NC

NJ

NY

OH

OK

PA

TN

TX

WI