Trial Information

Comparison of Ara-c 12 gm/m2 vs 18 gm/m2 Per Cycle for 3 Cycles Each as Consolidation in AML ; An Open Label Randomized Non-inferiority Study

Objectives

- To compare the efficacy of two different doses of Cytarabine during consolidation
therapy for newly diagnosed patients of Non APML - Acute Myeloid Leukemia who are in CR
post induction

- To compare the toxicity of the two different Cytarabine doses

Primary end point

- Relapse free survival at 1 yr from randomization

- Relapse will be defined as >5 % leukemic blasts in the marrow aspirate or new
extramedullary disease anytime after randomization

Secondary end points

- Overall survival

- Median time to relapse

- Toxicity- Haematological and Non -Haematological

Inclusion criteria

- Confirmation of Acute Myeloid Leukemia by morphologic, immunophenotypic analysis

- Suitable for HIDAC as consolidation

- AML with underlying MDS will be included

Exclusion criteria

- Previous AML chemotherapy [Hydroxyurea - not an exclusion.]

- CML-BC

- Concurrent active malignancy

- HIV infection, Uncontrolled Hepatitis B/C

- Patients being considered for upfront PBSCT (before completion of CONSOLIDATION)

- Serum Bilirubin > 2

- APML

- Delayed recovery of blood counts /persistent active infection > 45 days from start of
induction

- Patients receiving reinduction with HIDAC

- Therapy related AML Methodology

- The period of enrollment will be from July 1, 2012 to September 30 ,2013

- Baseline information will be recorded in a preformulated proforma designed for analysis
at a later date

Treatment

- Standard 3 + 7 INDUCTION with Daunomycin and Cytarabine with DNR at 60- 90 mg/m2 as per
the PS and comorbidities/active infections at presentation

- Bone marrow examination - D+ 28 of induction or earlier if needed . Patients not in
CR - reinduction regimen as per discretion of treating physician

- Patients in complete morphological remission ( after 1 or 2 inductions) : will receive
consolidation with HIDAC and will be randomized into the two study arms after written
Informed Consent: Arm A and B with 90 patients in each arm Arm A will receive HIDAC at
18 gm/m2/cycle for 3 cycles , i.e. 3 gm/m2 BD , Day 1,3,5 Arm B will receive HIDAC at
12 gm/m2/cycle for 3 cycles , i.e. 2 gm/m2 BD , Day 1,3,5

sample size

- Assuming a RFS of 60 % at 1 yr in each arm and keeping a non-inferiority margin of 20
% , Alpha at 5 % ,75 patients are required in each arm on the basis of statistical
calculation.

- 15 patients added in each arm to account for losses

- Total required in each arm = 90

- ANC> 1000 , Platelet count > 1 lac required to start HIDAC

- Detailed information of the course of all the chemotherapy cycles will be recorded
including-

1. toxicity

2. details of antimicrobials

3. supportive care ( including transfusions)

4. Use of growth factors

- Cytogenetic analysis using standard technique of chromosomal banding

- Molecular analysis for mutation of FLT3-ITD will be performed

- Risk stratification will be done as per guidelines

- Patients in both arms will be kept under close follow up and will be assessed with
blood counts /PS , 2 monthly / or earlier as clinically indicated

Statistical Analysis

- Qualitative data will be analyzed using the Chi-square test

- Quantitative data will be compared by using t-test /Mann Whitney test

- Besides this survival analysis will be carried out.