Safety and Efficacy Study of Ara-c at 18 gm/m2 Versus 12 gm/m2 for 3 Cycles Each in AML Consolidation

Acute Myeloid Leukemia Clinical Trial

— Ara-c  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01615757
• Other study ID #: AML HIDAC, AIIMS
• Status: Recruiting
• Phase: Phase 3
• First received: June 5, 2012
• Last updated: September 13, 2012
• Start date: August 2012
• Est. completion date: September 2014

Study information

• Verified date: September 2012
• Source: All India Institute of Medical Sciences, New Delhi
• Contact: Prashant Mehta, MD
• Phone: 09013590847
• Email: prashantcipher[@]yahoo.co.in
• Is FDA regulated: No
• Health authority: India: Indian Council of Medical Research
• Study type: Interventional

Clinical Trial Summary

The study will be conducted in the Department of Medical Oncology and Department of Haematology , AIIMS, Delhi. A total of 180 patients of Acute Myeloid Leukemia who are in complete remission after induction chemotherapy will be enrolled into the study and will be further randomized to the two study arms . ARM- A will receive Ara-c at 18 gm /m2 for 3 cycles and ARM -B will receive Ara-c at 12 gm/m2 for 3 cycles according to the study protocol. Aim of the study will be to compare the efficacy of the two doses in terms of the relapse free survival and overall survival as well as time to relapse and toxicity /treatment related morbidity.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• Ara-c
IV formulation, administered as a 2 hr infusion in 1 pint of normal saline, BD on D1,3,5 at 3 gm/m2 /dose
• Ara-c
IV formulation, administered as a 2 hr infusion in 1 pint of normal saline, BD on D1,3,5 at 2 gm/m2 /dose

Locations

Country	Name	City	State
India	AIIMS	Delhi

Sponsors (1)

Lead Sponsor	Collaborator
All India Institute of Medical Sciences, New Delhi

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relapse free survival at 1 yr of follow up		1 year	No
Secondary	Toxicity- Haematological and Non -Haematological	The following variables will be compared in the two arms to -; -Nadir blood counts,Ara c related fever ,Allergic or skin reactions,Alopecia,Diarrhea ,Stomatitis,Bleeding ,Febrile neutropenia,Infection(fungal /bacterial/viral),Liver related event,ocular toxicity,Neurologic event,Peripheral neuropathy,Cerebral/Cerebellar toxicity,Transfusions,Time to recovery of platelets,Time to recovery of neutrophils,Duration of Hospital stay,Emergency visits,Deaths,Use of growth factors	at 1 yr	Yes