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

NCT ID: NCT01615757

Last Updated: 2012-09-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

180 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-08-31

Study Completion Date

2014-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Acute Myeloid Leukemia

Keywords

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AML Acute Myeloid Leukemia Cytarabine dose Ara-c dose Consolidation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

Ara-c

Intervention Type DRUG

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

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

Group Type ACTIVE_COMPARATOR

Ara-c

Intervention Type DRUG

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

Interventions

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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

Intervention Type 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

Intervention Type DRUG

Other Intervention Names

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Cytosar, Cytarabine Cytosar, Cytarabine

Eligibility Criteria

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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
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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All India Institute of Medical Sciences

OTHER

Sponsor Role lead

Responsible Party

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Prashant Mehta

Senior Resident , Department of Medical Oncology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Prashant Mehta, MD

Role: PRINCIPAL_INVESTIGATOR

AIIMS, Delhi, India

Vinod Raina, MD

Role: STUDY_CHAIR

AIIMS, Delhi

Locations

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AIIMS

Delhi, National Capital Territory of Delhi, India

Site Status RECRUITING

Countries

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India

Central Contacts

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Prashant Mehta, MD

Role: CONTACT

Phone: 09013590847

Email: [email protected]

Facility Contacts

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Prashant Mehta, MD

Role: primary

Other Identifiers

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AML HIDAC, AIIMS

Identifier Type: -

Identifier Source: org_study_id