a prospective randomized comparison of hdac vs ad in the induction chemothrapy for aml.

Conditions: Acute Myeloid Leukemia

Summary: this trial is a single-center, non-blind, two-arm randomized prospective controlled trial to compare the effectiveness of two induction chemotherapy regimens (high-dose cytarabine plus daunorubicin \[hdac\] vs. cytarabine plus high-dose daunorubicin \[ad\]) in acute myeloid leukemia (aml). the primary hypothesis of the study is that ad is superior to hdac in terms of event-free survival (efs, time from registration to induction failure, relapse, or death).

* induction chemotherapy * arm i \[hdac\]: cytarabine 3.0 g/m2 q12hr 3-hour iv infusion on days 1, 3, 5 plus daunorubicin 45 mg/m2/day continuous iv infusion for 3 days (d1-3). * arm ii \[ad\]: cytarabine 200 mg/m2/day continuous iv infusion for 7 days (d1-7) plus daunorubicin 90 mg/m2/day continuous iv infusion for 3 days (d1-3). * interim bone marrow examination interim bone marrow aspiration and biopsy will be done between 14 and 21 days after start of induction chemotherapy. if bone marrow has blasts \< 10%, no additional chemotherapy will be given until the recovery of blood counts (absolute neutrophil counts rise over 1,000/μl and platelet counts over 100,000/μl) or post-induction day 35, when bone marrow examination will be repeated to evaluate cr. after the marrow examination, re-induction course will be given. if interim bone marrow examination shows persistent leukemia (blasts ≥ 10%), re-induction course could be given. patients who did not attain cr after the re-induction chemotherapy will be eliminated from the study. * re-induction chemotherapy * cytarabine 200 mg/m2/day iv infusion for 5 days (d1-5) plus daunorubicin 45 mg/m2/day iv infusion for 2 days (d1-2) post-remission consolidation chemotherapy * adverse risk group: up to 3 courses of intermediate-dose cytarabine (1.0 g/m2/day iv for 5 days \[d1-5\]) plus etoposide (150 mg/m2/day iv for 3 days \[d1-3\]) * favorable/intermediate risk group: up to 3 courses of high-dose cytarabine (3.0 g/m2/day q12 hr iv for 3 days \[d1, 3, 5\]) * autologous or allogeneic hematopoietic cell transplantation (hct) can be performed based on the risk of relapse. * the bone marrow examination will be done after the completion of consolidation chemotherapy or before hct.

Eligibility criteria:
inclusion criteria: * previously-untreated aml (≥ 20% blasts in bone marrow and/or peripheral blood) * age of 15 years or older, 60 years or younger * adequate performance status (karnofsky score of 50 or more) * adequate hepatic and renal function (ast, alt, and bilirubin \< 2.5 x upper normal limit and creatinine \< 2.0 mg/dl \& creatinine clearance ≥ 50 ml/min). elevation of ast or alt due to hepatic infiltration of leukemic cells will be permitted. * adequate cardiac function (left ventricular ejection fraction ≥45% on heart scan or echocardiogram) * signed informed consent exclusion criteria: * patients with history of chemotherapy for leukemia or cytarabine and anthracycline treatment for any malignancy. hydroxyurea for reduction of leukemic cell burden before induction chemotherapy will be permitted. * patients with acute promyelocytic leukemia * patients with blast crisis of chronic myeloid leukemia * patients with central nervous system (cns) leukemia or granulocytic sarcoma without bone marrow involvement * presence of uncontrolled and/or severe medical condition (infection, bleeding, cardiovascular disease including myocardial infarction within previous 6 months.) * nursing women, pregnant women, women of childbearing potential who do not want adequate contraception * patients with a diagnosis of prior malignancy unless disease-free for at least 5 years following therapy with curative intent (except curatively treated nonmelanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia)

Keywords: hdac vs ad