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RecruitingLast updated: 26 February 2024

ENHANCE-3: This phase III study is trying to understand the effectiveness of immunotherapy (magrolimab) versus placebo, in combination with targeted therapy and chemotherapy (venetoclax and azacitidine) in people with newly diagnosed, previously untreated acute myeloid leukaemiaA Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Magrolimab Versus Placebo in Combination With Venetoclax and Azacitidine in Newly Diagnosed, Previously Untreated Patients With Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy

Clinical summary

Summary

Eligible participants will be randomly allocated to either the Experimental Arm or the Placebo Comparator Arm.

In the Experimental Arm, participants will receive magrolimab + venetoclax + azacitidine. Magrolimab will be administered intravenously at a dose of 1mg/kg priming dose on Days 1 and 4; 15mg/kg on Day 8; and 30mg/kg on Days 11, 15 and then every week for 5 doses and every 2 weeks after that. Venetoclax will be administered orally at a dose of 100mg on Cycle 1 Day 1, 200mg on Cycle 1 Day 2, 400mg on Cycle 1 Day 3 and daily after that. Azacitidine will be administered either subcutaneously or intravenously, at a dose of 75mg/m^2 on Days 1-7 or Days 1-5 and 8-9 of each cycle. Each cycle is 28 days.

In the Placebo Comparator Arm, participants will receive a magrolimab placebo + venetoclax + azacitidine. Magrolimab placebo will be given intravenously on Days 1, 4, 8, 11 and 15, then every week for 5 doses and every 2 weeks after that. Venetoclax and Azacitidine will be administered the same as in the Experimental Arm.

Conditions

This trial is treating patients with acute myeloid leukaemia

Cancer

Blood Cancers Haematological

Age

People18+

Phase

III

Trial Acronym

ENHANCE-3

More information

Trial Identifiers

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Trial sponsor

Gilead Sciences, Inc.

Scientific Title

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Magrolimab Versus Placebo in Combination With Venetoclax and Azacitidine in Newly Diagnosed, Previously Untreated Patients With Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy

Eligibility

Inclusion

  • Previously untreated individuals with histological confirmation of acute myeloid leukemia (AML) by World Health Organization (WHO) criteria who are ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to age, or comorbidity. Individuals must be considered ineligible for intensive chemotherapy, defined by the following:

    • ≥ 75 years of age; Or
    • ≥ 18 to 74 years of age with at least 1 of the following comorbidities:

      • Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3
      • Diffusing capacity of the lung of carbon monoxide ≤ 65% or forced expiratory volume in 1 second ≤ 65%
      • Left ventricular ejection fraction ≤ 50%
      • Baseline creatinine clearance ≥ 30 mL/min to < 45 mL/min calculated by the Cockcroft Gault formula or measured by 24-hour urine collection
      • Hepatic disorder with total bilirubin > 1.5 x upper limit of normal (ULN)
      • Any other comorbidity that the investigator judges to be incompatible with intensive chemotherapy
    • ECOG performance status:

      • Of 0 to 2 for individuals ≥ 75 years of age Or
      • Of 0 to 3 for individuals ≥ 18 to 74 years of age
  • Individuals with white blood cell (WBC) count ≤ 20 x 10^3/μL prior to randomization. If the individual's WBC is > 20 x10^3/μL prior to randomization, the individual can be enrolled, assuming all other eligibility criteria are met. However, the WBC should be ≤ 20 x 10^3/μL prior to the first dose of study treatment and prior to each magrolimab/placebo dose during Cycle 1.

    • Note: Individuals can be treated with hydroxyurea and/or leukapheresis prior to randomization and throughout the study to reduce the WBC to ≤ 20 x 10^3/μL to enable eligibility for study drug dosing
  • Hemoglobin must be ≥ 9 g/dL prior to initial dose of study treatment

    • Note: Transfusions are allowed to meet hemoglobin eligibility
  • Pretreatment blood cross-match completed

Exclusion

  • Prior treatment with any of the following:

    • cluster of differentiation 47 (CD47) or signal regulatory protein alpha (SIRPα)-targeting agents
    • Antileukemic therapy for the treatment of AML (eg, hypomethylating agents (HMAs), low-dose cytarabine, and/or venetoclax), excluding hydroxyurea

      • Note: Individuals with prior MDS who have not received prior HMAs or venetoclax or chemotherapeutic agents for MDS may be enrolled in the study. Prior treatment with myelodysplastic syndrome (MDS) therapies including, but not limited to lenalidomide, erythroid-stimulating agents, or similar red blood cell negative (RBC-), white blood cell negative (WBC-), or platelet-direct therapies or growth factors is allowed for these individuals.
  • Clinical suspicion of or documented active central nervous system (CNS) involvement with AML
  • Individuals who have acute promyelocytic leukemia
  • Second malignancy, except MDS, treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which individuals are not on active anticancer therapies and have had no evidence of active malignancy for at least 1 year

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Inclusion

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

Exclusion

  • You have been diagnosed with a prior or secondary type of cancer.
  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria.

Ask your doctor if this trial could be right for you.

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