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No longer recruiting (closed or complete)Last updated: 7 February 2024

M16043 Viale-C: This phase III trial is evaluating the effectiveness of combining two chemotherapy drugs (Venetoclax with Low Dose Cytarabine) for patients with Acute Myeloid Leukaemia that have not previously received treatment and are ineligible for intense chemotherapyA Randomized, Double-Blind, Placebo Controlled Phase 3 Study of Venetoclax Co-Administered with Low Dose Cytarabine Versus Low Dose Cytarabine in Treatment Naïve Patients with Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy

Trial purpose

Medical clipboardCancer treatment

Tumor type

Blood Cancers Haematological

Age

People18+

Trial acronym

M16043 Viale-C

Clinical summary

Summary

This study aims to assess the benefits of adding venetoclax to a low dose cytarabine chemotherapy regime for Acute Myeloid Leukaemia. Patients eligible to participate in this trial will be treated daily with venetoclax, or a placebo, for 28 days and low dose cytarabine for the first 10 days of the 28-day cycle.

Conditions

This trial is treating people with Acute Myeloid Leukaemia

Eligibility

Inclusion

  1. Participant must have histological confirmation of acute myeloid leukemia (AML) by World Health Organization criteria, be ineligible for intensive induction chemotherapy and either be:

    • ≥ 75 years of age OR
    • ≥ 18 to 74 years of age and fulfill at least one criteria associated with lack of fitness for intensive induction chemotherapy:

      • Eastern Cooperative Oncology Group (ECOG) performance status of 2 - 3
      • Cardiac history of congestive heart failure (CHF) requiring treatment or ejection fraction ≤ 50% or chronic stable angina
      • Diffusing capacity of the lung for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume in 1 second (FEV1) ≤ 65%
      • Creatinine clearance ≥ 30 mL/min to < 45 ml/min
      • Moderate hepatic impairment with total bilirubin > 1.5 to ≤ 3.0 × upper limit of normal (ULN)
      • Other comorbidity that the physician judges to be incompatible with conventional intensive chemotherapy which must be reviewed and approved by the study medical monitor before study enrollment
  2. Participant must have an ECOG performance status:

    • of 0 to 2 for subjects ≥ 75 years of age OR
    • of 0 to 3 for subjects between 18 to 74 years of age
  3. Participant must have a projected life expectancy of at least 12 weeks.
  4. Participant must have adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24-hour urine collection.
  5. Participant must have adequate liver function as demonstrated by:

    • aspartate aminotransferase (AST) ≤ 3.0 × ULN*
    • alanine aminotransferase (ALT) ≤ 3.0 × ULN*
    • bilirubin ≤ 1.5 × ULN*

      • Subjects who are < 75 years of age may have bilirubin of ≤ 3.0 × ULN

    (*Unless considered to be due to leukemic organ involvement.)

  6. Female participants must be either postmenopausal defined as:

    • Age > 55 years with no menses for 12 or more months without an alternative medical cause.
    • Age ≤ 55 years with no menses for 12 or more months without an alternative medical cause AND a follicle-stimulating hormone (FSH) level > 40 IU/L.

    OR

    • Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).

    OR

    • A woman of childbearing potential (WOCBP) practicing at least one protocol specified method of birth control starting at Study Day 1 through at least 180 days after the last dose of study drug.
  7. Male participants who are sexually active, must agree, from Study Day 1 through at least 180 days after the last dose of study drug, to practice protocol specified methods of contraception. Male subjects must agree to refrain from sperm donation from initial study drug administration through at least 180 days after the last dose of study drug.
  8. Females of childbearing potential must have negative results for pregnancy test performed:

    • At Screening with a serum sample obtained within 14 days prior to the first study drug administration, and
    • Prior to dosing with urine sample obtained on Cycle 1 Day 1, if it has been > 7 days since obtaining the serum pregnancy test results.
    • Subjects with borderline pregnancy tests at Screening must have a serum pregnancy test ≥ 3 days later to document continued lack of a positive result.
  9. Participant must voluntarily sign and date an informed consent form, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.

Exclusion

  1. Participant has received any prior treatment for AML with the exception of hydroxyurea, allowed through the first cycle of study treatment. Note: Prior treatment for myelodysplastic syndrome is allowed except for use of cytarabine.
  2. Participant had an antecedent myeloproliferative neoplasm (MPN) including myelofibrosis, essential thrombocytosis, polycythemia vera, or chronic myelogenous leukemia (CML) with or without BCR-ABL 1 translocation and AML with BCR-ABL 1 translocation.
  3. Participants that have acute promyelocytic leukemia (APL).
  4. Participant has known central nervous system (CNS) involvement with AML.
  5. Participant has known human immunodeficiency virus (HIV) infection (due to potential drug-drug interactions between antiretroviral medications and venetoclax). HIV testing will be performed at Screening, if required per local guidelines or institutional standards.
  6. Participant is known to be positive for hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Inactive hepatitis carrier status or low viral hepatitis titer on antivirals (non-exclusionary medications) are not excluded.
  7. Participant has received strong or moderate cytochrome P450 3A4 (CYP3A) inducers 7 days prior to the initiation of study treatment.

    • Chinese subjects are excluded from receiving strong and/or moderate CYP3A inhibitors 7 days prior to the initiation of study treatment through the end of intensive pharmacokinetic (PK) collection (24 hours post dose on Cycle 1 Day 10).
  8. Participant has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or star fruit within 3 days prior to the initiation of study treatment.
  9. Participant has cardiovascular disability status of New York Heart Association Class > 2. Class 2 is defined as cardiac disease which subjects are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or angina pain. Class 3 is defined as cardiac disease which subjects are comfortable at rest but less than ordinary activity causes fatigue, palpitation, or dyspnea. Class 4 is defined as cardiac disease which subjects have an inability to carry on any physical activity without discomfort, symptoms of heart failure at rest, and if any physical activity is undertaken then discomfort increases.
  10. Participant has chronic respiratory disease that requires continuous oxygen, or significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, any other medical condition or known hypersensitivity to any of the study medications including excipients of LDAC that in the opinion of the investigator would adversely affect his/her participating in this study.
  11. Participant has a malabsorption syndrome or other condition that precludes enteral route of administration.
  12. Participant exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal).
  13. Participant has a history of other malignancies prior to study entry, with the exception of:

    • Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
    • Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
    • Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
  14. Participant has a white blood cell count > 25 × 10^9/L. (Note: hydroxyurea administration or leukapheresis is permitted to meet this criterion).
  15. Previous treatment with venetoclax and/or current participation in any other research study with investigational products.

Inclusion

  • You are able to swallow medication by mouth.
  • You have been diagnosed with cancer, but have not received any treatment.

Exclusion

  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
  • You are currently being treated on a clinical trial.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:

Trial sponsor

AbbVie

Scientific Title

A Randomized, Double-Blind, Placebo Controlled Phase 3 Study of Venetoclax Co-Administered with Low Dose Cytarabine Versus Low Dose Cytarabine in Treatment Naïve Patients with Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy

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