Clinical trial NCT03507842: A Prospective Randomized Comparison of HDAC Vs AD in the Induction Chemothrapy for AML.
Official title: A Prospective Randomized Comparison of High-dose Cytarabine an High-dose Daunorubicin in the Induction Chemothrapy for Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE3
Conditions: Acute Myeloid Leukemia
Keywords: HDAC vs AD
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2018-04-25
Enrollment: 380
Sex: ALL
Minimum age (years): 15
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Cumulative incidence of relapse
timeFrame: 3 years
Secondary outcomes:
measure: Event-free survival
timeFrame: 3years
measure: Overall survival
timeFrame: 3years
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center, University of Ulsan College of Medicine
Study officials:
affiliation: Asan Medical Center
name: Je-Hwan Lee, MD
role: PRINCIPAL_INVESTIGATOR
References: