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

September 13, 2012 updated by: Prashant Mehta, All India Institute of Medical Sciences, New Delhi

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Anticipated)

180

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
      • Delhi, India, 110001
        • Recruiting
        • AIIMS
        • Contact:
        • Principal Investigator:
          • Prashant Mehta, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm B, Ara-c - 12 gm/m2
Arm B will receive HIDAC at 12 gm/m2/cycle for 3 cycles , i.e. 2 gm/m2 BD , Day 1,3,5
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
Other Names:
  • Cytosar, Cytarabine
Drug: 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
Other Names:
  • Cytosar, Cytarabine
Active Comparator: Arm A. Ara-c 18 gm/m2
Arm A will receive HIDAC at 18 gm/m2/cycle for 3 cycles , i.e. 3 gm/m2 BD , Day 1,3,5
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
Other Names:
  • Cytosar, Cytarabine
Drug: 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
Other Names:
  • Cytosar, Cytarabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Relapse free survival at 1 yr of follow up
Time Frame: 1 year
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Toxicity- Haematological and Non -Haematological
Time Frame: at 1 yr

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

All India Institute of Medical Sciences, New Delhi

Investigators

  • Principal Investigator: Prashant Mehta, MD, AIIMS, Delhi, India
  • Study Chair: Vinod Raina, MD, AIIMS, Delhi

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2012

Primary Completion (Anticipated)

September 1, 2014

Study Completion (Anticipated)

September 1, 2014

Study Registration Dates

First Submitted

June 5, 2012

First Submitted That Met QC Criteria

June 7, 2012

First Posted (Estimate)

June 11, 2012

Study Record Updates

Last Update Posted (Estimate)

September 17, 2012

Last Update Submitted That Met QC Criteria

September 13, 2012

Last Verified

September 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AML HIDAC, AIIMS

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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