Phase III Study of Induction and Consolidation Chemotherapy With Venetoclax in Patients With Newly Diagnosed AML or MDS-EB-2

Sponsor
University of Ulm
Study ID
NCT04628026
Phase
PHASE3
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Venetoclax — DRUG
    Venetoclax will be administered in Induction cycle 1, Induction cycle 2 and in the chemo consolidation therapy in addition to the standard chemotherapy
  • Placebo — DRUG
    Placebo will be administered in Induction cycle 1, Induction cycle 2 and in the chemo consolidation therapy in addition to the standard chemotherapy
  • Standard chemotherapy — COMBINATION_PRODUCT
    Induction cycle 1: Patients will receive cytarabine 200 mg/m2 continuous IV (days 1-7) and daunorubicin 60 mg/m2 IV (days 1-3). Induction cycle 2: Patients ≤ 60 yrs will receive cytarabine 1000 mg/m2 BID (3h IV), days 1-4, and daunorubicin 60 mg/m2 IV (days 1-3). Patients \>60 yrs will receive cytarabine 1000 mg/m2 BID (3h IV), days 1-4 without daunorubicin. Consolidation chemotherapy with intermediate doses of cytarabine. Patients ≤60 yrs will receive up to 3 cycles of IDAC (single dose 1500 mg/m2 every 12 hours, days 1-3). Patients who are \>60 yrs will receive up to 3 cycles of IDAC with single doses of 1000 mg/m2, every 12 hours, days 1-3. In patients \>60 yrs less than 3 cycles of IDAC or dose-reduced IDAC (500 mg/m2 per single dose) may be given based on an individual risk assessment.
  • Allogeneic stem cell transplantation — OTHER
    Generally, patients will proceed to allogeneic HCT upon completion of remission induction chemotherapy. It is however allowed, as per investigator's discretion, for a patient to receive 'bridging' consolidation chemotherapy in exceptional cases of delay towards transplantation. At baseline, HLA-compatible donor search must be initiated as soon as possible, first among siblings and second in the world donor bank for unrelated donors or cord blood. In order to avoid inappropriate delay in cases where no suitable sibling is present, high-resolution HLA typing should be performed immediately after registration, enabling a more rapid matched-unrelated donor search. In case no sibling or unrelated donor can be identified, haploidentical allogeneic HCT is allowed. Conditioning and GVHD prophylaxis will take place according to institutional guidelines. Patients who undergo allogeneic HCT will not receive venetoclax during conditioning, engraftment or after hematologic recovery.

Study Details

A Randomized, Placebo-Controlled Phase III Study of Induction and Consolidation Chemotherapy With Venetoclax in Adult Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome With Excess Blasts-2

Key Dates

Start date
Sep 13, 2022
Status verified
Mar 2026
Primary completion
Mar 31, 2029
Completion
Feb 29, 2032

Study Design

Enrollment
650 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: 1
    standard chemotherapy in combination with venetoclax
  • Placebo Comparator: 2
    standard chemotherapy in combination with placebo

Primary Outcome Measure

Event Free Survival (EFS) [ Time Frame: 6 months/16 months after inclusion of last patient ]

Central Contacts

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