Acute Myeloid Leukemia
Conditions
Keywords
HDAC vs AD
Brief 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).
Detailed description
* 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.
Interventions
High dose 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).
DRUGCytarabine
cytarabine 200 mg/m2/day continuous iv infusion for 7 days (D1-7)
DRUGHign dose Daunorubicin
Hign dose Daunorubicin 90 mg/m2/day continuous iv infusion for 3 days (D1-3).
Sponsors
Asan Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to 60 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative incidence of relapse | 3 years | defined for all patients achieving CR; measured from the date of CR achievement until the date of relapse; patients not known to have relapsed are censored on the date they were last examined; patients who died without relapse are counted as a competing cause of failure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event-free survival | 3years | Defined for all patients; measured from the starting date of registration to the date of induction treatment failure, or relapse from CR, or death from any cause; patients not known to have any of these events are censored on the date they were examined |
| Overall survival | 3years | Defined for all patients; measured from the starting date of registration to the date of death from any cause-patients not known to have died at last follow-up are censored on the date they were last known to be alive |
Countries
South Korea
Outcome results
None listed