Clinical trial NCT00474006: High Dose Daunorubicin Vs. Standard Dose Daunorubicin in Induction Treatment of AML
Official title: A RANDOMIZED COMPARISON OF TWO DIFFERENT DOSAGES OF DAUNORUBICIN IN INDUCTION TREATMENT OF ACUTE MYELOGENOUS LEUKEMIA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: ACUTE MYELOGENOUS LEUKEMIA
Lead sponsor: Cooperative Study Group A for Hematology
Sponsor class: NETWORK
First posted: 2007-05-16
Enrollment: 398
Sex: ALL
Minimum age (years): 15
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Toxicities, complete remission rate, duration of complete remission, disease-free survival, overall survival
timeFrame: 10years
Secondary outcomes:
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Songpa-gu
Study officials:
affiliation: Asan Medical Center, ROK
name: Je Hwan Lee, professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lee JH, Joo YD, Kim H, Bae SH, Kim MK, Zang DY, Lee JL, Lee GW, Lee JH, Park JH, Kim DY, Lee WS, Ryoo HM, Hyun MS, Kim HJ, Min YJ, Jang YE, Lee KH; Cooperative Study Group A for Hematology. A randomized trial comparing standard versus high-dose daunorubicin induction in patients with acute myeloid leukemia. Blood. 2011 Oct 6;118(14):3832-41. doi: 10.1182/blood-2011-06-361410. Epub 2011 Aug 9.