A Prospective Randomized Comparison of HDAC Vs AD in the Induction Chemothrapy for AML.

Phase 3Enrolling By InvitationNCT03507842

Asan Medical Center380 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

380

Conditions

Acute Myeloid Leukemia

Interventions

High dose CytarabineDRUG

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).

CytarabineDRUG

cytarabine 200 mg/m2/day continuous iv infusion for 7 days (D1-7)

Hign dose DaunorubicinDRUG

Hign dose Daunorubicin 90 mg/m2/day continuous iv infusion for 3 days (D1-3).

Eligibility

Sex: ALLMin age: 15 YearsMax age: 60 Years

Medical Language ↔ Plain English

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)

Locations (1)

Asan Medical Center, University of Ulsan College of Medicine

Seoul, South Korea

Outcomes

Primary Outcomes

Cumulative incidence of relapse

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

Time frame: 3 years

Secondary Outcomes

Event-free survival

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

Time frame: 3years

Overall survival

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

Time frame: 3years

Data from ClinicalTrials.gov

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