High Dose Daunorubicin Vs. Standard Dose Daunorubicin in Induction Treatment of AML

Study Overview
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Brief Summary
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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.

Detailed Description
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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. 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. 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.

Official Title
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A RANDOMIZED COMPARISON OF TWO DIFFERENT DOSAGES OF DAUNORUBICIN IN INDUCTION TREATMENT OF ACUTE MYELOGENOUS LEUKEMIA

Conditions
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ACUTE MYELOGENOUS LEUKEMIA

Intervention / Treatment
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* Drug: arm II


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: arm I<br>Cytarabine 200 mg/m2/d civ x 7 days Daunorubicin 45 mg/m2/d civ x 3 days | Drug: arm II<br>* Cytarabine 200 mg/m2/d civ x 7 days Daunorubicin 90 mg/m2/d civ x 3 days<br>* Other names: higher dose of Daunorubicin (ArmI);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicities, complete remission rate, duration of complete remission, disease-free survival, overall survival | The effects will be evaluated in terms of toxicities, complete remission rate, duration of complete remission, disease-free survival, and overall survival. | 10years |