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

NCT ID: NCT03507842

Last Updated: 2025-03-17

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE3
• Total Enrollment: 380 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-01
• Study Completion Date: 2028-12-31

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.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

High dose Cytarabine

Intervention Type: DRUG

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 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).

Group Type: EXPERIMENTAL

Cytarabine

Intervention Type: DRUG

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

Hign dose Daunorubicin

Intervention Type: DRUG

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

Interventions

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).

Intervention Type: DRUG

Cytarabine

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

Intervention Type: DRUG

Hign dose Daunorubicin

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

Intervention Type: DRUG

Other Intervention Names

HDAC; AD; AD

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)

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Asan Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Je-Hwan Lee

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Je-Hwan Lee, MD

Role: PRINCIPAL_INVESTIGATOR

Asan Medical Center

Locations

Asan Medical Center, University of Ulsan College of Medicine

Seoul, , South Korea

Countries

South Korea

Other Identifiers

AMC_HDAC vs AD in AML

Identifier Type: -

Identifier Source: org_study_id