RecruitingPhase 2

Induction and Consolidation With Fludarabine, Cytarabine, Idarubicin, and Venetoclax for the Treatment of Acute Myeloid Leukemia

A Phase II Randomized Clinical Trial of Venetoclax Combined With FLAG IDA Induction and Consolidation Compared to Standard of Care for Newly Diagnosed 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 to 65 Years
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

  • Time periods mentioned: 2 years
  • Procedures mentioned: Questionnaires, Blood draws, Biopsies

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "Assess participant quality of life (QoL) using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30)."
  • "Patients also undergo bone marrow aspiration and biopsy and blood sample collection throughout the trial."
  • "After completion of study treatment, patients are followed up at 30 days and then every 3 months for 2 years."
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 compares fludarabine, cytarabine, idarubicin, and venetoclax with chemotherapy using cytarabine and daunorubicin. Treatment aims to get the cancer under control, then kill any cancer cells left behind. It is for adults ages 18–65 with newly diagnosed acute myeloid leukemia (AML), a blood cancer, or certain cases of myelodysplastic syndrome (MDS), a bone marrow disease.

This phase II trial compares induction and consolidation therapy with fludarabine, cytarabine, idarubicin, and venetoclax to cytarabine and daunorubicin induction and cytarabine consolidation for the treatment of acute myeloid leukemia (AML). Patients with AML often receive induction and consolidation therapy. Induction therapy is given first to get the patient's AML under control (remission). Consolidation therapy is given after the cancer has disappeared following the initial therapy. Consolidation therapy is used to kill any cancer cells that may be left in the body. Chemotherapy drugs, such as fludarabine, cytarabine, idarubicin, and daunorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving fludarabine, cytarabine, idarubicin, and venetoclax for induction and consolidation therapy may be more effective in treating AML.

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

Eligibility

Who can join

  • Be ages 18–65, understand the study, and give written consent. People of all genders, races, and ethnic groups may join.
  • Have newly diagnosed, untreated AML or MDS with at least 10% blasts (young blood cells) in the bone marrow. Some treatment to lower blood cell counts is allowed.
  • Be fully active or able to do light work, even if hard physical activity is limited.
  • Be willing to have a stem cell transplant, which replaces blood-forming cells.
  • Be able to take medicine by mouth or feeding tube.
  • Meet the study’s blood count, heart, kidney, and liver test requirements.
  • Follow the study schedule and lifestyle rules, give bone marrow samples, and accept support care, including blood transfusions.
  • If able to become pregnant, have a negative pregnancy test within 3 days before treatment. Follow birth control and egg or sperm donation rules during treatment and for 3–6 months afterward, as required.

Who can't join

  • Have acute promyelocytic leukemia (APL) or certain leukemia gene changes: FLT3 ITD or core binding factor changes. FLT3 TKD changes are allowed.
  • Have AML in the brain or spinal cord, or another active cancer within the past 5 years. Some treated early skin cancers and doctor-approved exceptions are allowed.
  • Have recent major surgery, graft-versus-host disease (donor cells attacking the body), or a transplant using your own stem cells within the study’s time limits.
  • Have recent chemotherapy, study treatment, or a BCL-2 blocker, or take medicines that interfere with the study drugs. Timing rules and some exceptions apply. Allergies to study drugs or their ingredients also exclude you.
  • Have serious heart problems, a heart attack within 6 months, or a white blood cell count above the study limit. Have swallowing or gut problems that prevent taking in or absorbing the drugs.
  • Have active liver disease, hepatitis B or C, or HIV treatment that interferes with study drugs. Some controlled infections or changes in HIV treatment are allowed.
  • Have an uncontrolled infection, or mental health or social issues that prevent following study rules. Controlled infections must meet the study’s stability requirements.
  • Be unwilling to stop breastfeeding during the study and for 6 weeks after the last study drug dose.

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

Official eligibility criteria

Inclusion Criteria: * Ability to comprehend the investigational nature of the study and provide written informed consent * Age 18 to ≤ 65 years (yrs), at the time of consent * All gender identities, races, or ethnicities are eligible * Newly documented, previously untreated diagnosis of AML or myelodysplastic syndrome (MDS) with marrow blasts ≥ 10%, in agreement with 2022 European LeukemiaNet criteria (ELN22) * Leukapheresis and treatment with cytarabine or hydroxyurea prior to study initiation is permitted for cytoreduction in patients with proliferative disease. NOTE: Treatment with cytarabine is limited to up to 2 grams total at least 14 days prior to starting on protocol defined therapy * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 * Willingness to undergo hematopoietic stem cell transplant (HSCT) * Ability to take medications by mouth or feeding tube * Adequate hematologic and organ function * Institutional standards, New York Heart Association (NYHA) criteria for cardiac function * Calculated creatinine clearance (according to the Cockcroft-Gault equation) \> 40 mL/min * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) ≤ 3 x upper limit of normal (ULN), unless considered due to leukemic involvement * Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x ULN, unless considered due to leukemic involvement * Total bilirubin ≤ 1.5 x ULN, unless due to Gilbert's disease or leukemic involvement * Willing and able to * Adhere to study schedule of activities and lifestyle restrictions while on treatment; * Provide bone marrow (BM) aspirate and core biopsy samples; AND * Accept supportive and prophylactic care for hematologic toxicities, infection, and immediate sequelae, including transfusions * Negative pregnancy test within 3 days of start of treatment for persons of childbearing potential (PCBP) * Based on animal studies and the known pharmacology of the study drugs, PCBP and sperm-producing participants who are sexually active with a PCBP must comply with study requirements for contraception * PCBP (participants and PCBP partners of participants) must agree to use an approved contraception and to refrain from donating / cryopreserving ova from cycle (C) 1 day (D) 1 until 6 months following the last dose of study treatment * Participants who produce viable sperm and who have intercourse with PCBP must agree to use an approved contraception method and to refrain from donating sperm from C1D1 until 3 months following the last dose of study treatment Exclusion Criteria: * Documented t(15;17) (acute promyelocytic leukemia \[APL\]), and/or mutation(s) to FLT3 ITD or core binding factor (CBF). Point mutations within the tyrosine kinase domain (FLT3 TKD) are allowed * Another active malignancy within the previous 5 years, except treated early stage carcinomas of the skin, or at the investigator's discretion * Known, active central nervous system (CNS) involvement with AML * Recent and significant medical interventions, such as major surgery within 28 days of start of treatment * GVHD or autologous stem cell transplant within 100 days of start of treatment * Currently receiving investigational therapy or chemotherapy within 28 days, or 5 half-lives, whichever is longer, with the exception of hydroxyurea or cytarabine for cytoreduction purposes * Prior treatment with a BCL 2 inhibitor within 12 months prior to the start of treatment * Use of strong or moderate CYP3A4 inducers or inhibitors or P-gp inhibitors within 2 days or 3 half-lives, whichever is longer, prior to start of treatment with venetoclax or at the discretion of the investigator if dose reductions, based on the interaction, have been specified * History of allergic response to any of the interventional agents or any excipients in the formulations * Inadequate organ function, including the following (or at the discretion of the investigator): * History of New York Heart Association (NYHA) class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) \< 40% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan * Unstable/uncontrolled angina pectoris, history of severe and/or uncontrolled ventricular arrhythmias, or history of myocardial infarction within the last 6 months * A white blood cell count (WBC) \> 25 x 10\^⁹/L * Known dysphagia in the absence of a feeding tube, short-gut syndrome, or other conditions or causes that would affect the ingestion and/or gastrointestinal absorption of drugs administered orally * Active hepatic disorder or documented positive hepatitis B or C virus (HBV/HCV, respectively) status, except in cases of undetectable HBV/HCV viral load for at least 3 months prior to the start of treatment. (Hepatitis B or C testing is not required for eligibility assessment.) * Individuals with positive serology for human immunodeficiency virus (HIV) who are undergoing treatment with highly active antiretroviral therapy (HAART) (or another therapy that may interfere with metabolism of study agents) are not eligible. If the HIV infection is controlled with another medication type or if an acceptable alternative HIV treatment can be substituted for HAART, enrollment may proceed * Uncontrolled infection. Participants with controlled infection must be afebrile and hemodynamically stable for at least 72 hours prior to start of treatment and must be amenable to alternate treatment if current treatment will interact with investigational regimen * Psychiatric illness/social situations that would limit compliance with study requirements * Unwillingness to stop breastfeeding. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding is not allowed throughout the study for 6 weeks after the last dose of study drug

Study sites (1)

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