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

Acute Myeloid Leukemia Clinical Trial

Official title:

A Prospective Randomized Comparison of High-dose Cytarabine an High-dose Daunorubicin in the Induction Chemothrapy for Acute Myeloid Leukemia

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03507842
• Other study ID #: AMC_HDAC vs AD in AML
• Status: Enrolling by invitation
• Phase: Phase 3
• Start date: March 1, 2018
• Est. completion date: December 31, 2020

Study information

• Verified date: January 2020
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Enrolling by invitation
• Enrollment: 380
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years to 60 Years

Eligibility

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)

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• 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).
• Cytarabine
cytarabine 200 mg/m2/day continuous iv infusion for 7 days (D1-7)
• Hign dose Daunorubicin
Hign dose Daunorubicin 90 mg/m2/day continuous iv infusion for 3 days (D1-3).

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center, University of Ulsan College of Medicine	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Asan Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	3 years
Secondary	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	3years
Secondary	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	3years