A Prospective Randomized Comparison of HDAC Vs AD in the Induction Chemothrapy for AML.
- Conditions
- Acute Myeloid Leukemia
- Interventions
- Registration Number
- NCT03507842
- Lead Sponsor
- Asan Medical Center
- 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.
Recruitment & Eligibility
- Status
- ENROLLING_BY_INVITATION
- Sex
- All
- Target Recruitment
- 380
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description high-dose daunorubicin Hign dose Daunorubicin cytarabine 200 mg/m2/day continuous iv infusion for 7 days (D1-7) plus high-dose daunorubicin 90 mg/m2/day continuous iv infusion for 3 days (D1-3). High-dose cytarabine High dose Cytarabine 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). high-dose daunorubicin Cytarabine cytarabine 200 mg/m2/day continuous iv infusion for 7 days (D1-7) plus high-dose daunorubicin 90 mg/m2/day continuous iv infusion for 3 days (D1-3).
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
Trial Locations
- Locations (1)
Asan Medical Center, University of Ulsan College of Medicine
🇰🇷Seoul, Korea, Republic of