High Dose Daunorubicin Vs. Standard Dose Daunorubicin in Induction Treatment of AML (ADcomparison)

Cooperative Study Group A for Hematology

Status and phase: Completed; Phase 3

Conditions: ACUTE MYELOGENOUS LEUKEMIA

Treatments: Drug: arm II

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT00474006

C-006

Details and patient eligibility

About

Determine the effects of escalated dose of daunorubicin in induction treatment of adult patients with acute myelogenous leukemia who are younger than 60 years of age.

Full description

1. Induction chemotherapy

   • For patients randomized to receive regular dose of Daunorubicin (Arm I) will be given Cytarabine 200 mg/m2/day by continuous iv infusion over 24 hours daily for 7 days along with Daunorubicin 45 mg/m2/day by continuous iv infusion over 24 hours daily for 3 days.
   • For patients randomized to receive higher dose of Daunorubicin (Arm II) will be given Cytarabine 200 mg/m2/day by continuous iv infusion over 24 hours daily for 7 days along with Daunorubicin 90 mg/m2/day by continuous iv infusion over 24 hours daily for 3 days.

2. Reinduction chemotherapy

   • Bone marrow aspiration and biopsy will be performed on day 14 of induction chemotherapy. If the bone marrow is hypoplastic and contains no more than 5% blast cells, further chemotherapy will be deferred and the marrow examination will be repeated at the time of ANC ≥ 1,500/μl and platelets ≥ 100,000/μl in the peripheral blood for the evaluation of complete remission. If more than 5% blast cells persist or if the marrow cellularity in the biopsy specimen exceeds 15%, a course of reinduction chemotherapy will be given.
   • Reinduction chemotherapy consists of Cytarabine 200 mg/m2/day by continuous iv infusion over 24 hours daily for 5 days along with Daunorubicin 45 mg/m2/day by continuous iv infusion over 24 hours daily for 2 days in both arms.

3. Postremission therapy

   • The same postremission therapy will be given to the patients in both arms.
   • Four courses of Cytarabine 3 g/m2 will be administered in a 3-hour iv infusion every 12 hours (twice daily) on days 1, 3, and 5 for a total of six doses per course. After the four courses of Cytarabine therapy, patients will receive two monthly treatments with Cytarabine (200 mg/m2/day by a 3-hour iv infusion for 5 days) and Daunorubicin (45 mg/m2 by rapid iv infusion on the first treatment day).
   • If patients have HLA-matched sibling or unrelated donors, allogeneic stem cell transplantation will be performed.
   • A complete remission will be defined as ≤ 5% blasts in a normocellular bone marrow with ANC ≥ 1,500/μl and platelets ≥ 100,000/μl in the peripheral blood and the disappearance of all blasts in bone marrow.

Enrollment: 398 patients

Sex: All

Ages: 15 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with newly diagnosed AML or RAEB
• 15 years of age or older, but younger than 60 years of age
• Adequate hepatic and renal function
• Normal cardiac function with LVEF ≥ 50% on MUGA scan or echocardiogram
• Written informed consent

Exclusion criteria

• promyelocytic leukemia or chronic myelogenous leukemia
• significant infection
• prior chemotherapy history for leukemia

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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398 participants in 1 patient group

arm I

Active Comparator group

Description:

Cytarabine 200 mg/m2/d civ x 7 days Daunorubicin 45 mg/m2/d civ x 3 days

Treatment:

Drug: arm II