A Prospective, Interventional Study Assessing Response to Cytarabine, Daunorubicin and Etoposide (ADE) for First Relapse of Paediatric Acute Myeloid Leukemia

RESPONSE TO CYTARABINE, DAUNORUBICIN AND ETOPOSIDE (ADE) AT FIRST RELASPE IN CHILDHOOD AML

One-third to one-half of patients with AML relapse and in general relapsed AML patients have a poor prognosis. The treatment of relapsed AML consists of induction chemotherapy followed by Allogenic Stem Cell Transplant (ASCT). However, at present there is no standard salvage chemotherapy regimen for relapsed AML, as no study has shown any one regimen to be significantly superior. Anthracyclines, Fludarabine, Etoposide and cytarabineare active agents in AMLand have been used as monotherapy and in combination in refractory and relapsed AML patients. According to previous studies the present CR rate of different regimens ranges from 50-70%. A retrospective analysis (unpublished) conducted at IRCH, AIIMS on relapsed AML patients treated with ADE (Cytarabine, Daunorubicin and Etoposide) chemotherapy showed the CR rates of approximately 70%. Therefore, we have planned this study to test the efficacy and toxicity of ADE induction chemotherapy in relapsed AML patients in a prospective manner.

Study Overview

• Status: Unknown
• Conditions: Acute Myeloid Leukemia, in Relapse
• Intervention / Treatment: Drug: ADE Protocol

• Study Type: Interventional
• Enrollment (Anticipated): 84
• Phase: Phase 2

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Either gender with age ≤18 years at initial diagnosis
2. AML(non-M3) patients at first relapse (medullary)

Exclusion Criteria:

1. Primary refractory AML &secondary AML
2. More than or equal to 2 relapses of AML
3. Symptomatic cardiac dysfunction (CTCAE Grade 3 or 4)
4. Active infection(pneumonia etc.)
5. Any other organ dysfunction (CTCAE Grade 4)
6. Patients not willing to consent for the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ADE arm; ADE arm Cytarabine (100mg/m2 d1-d10 BD), Daunorubicin (50mg/m2 d1-d3) and Etoposide (100 mg/m2 d1-5) over a period of 10 days	Drug: ADE Protocol; ADE chemotherapy Cytarabine (100mg/m2 d1-d10 BD), Daunorubicin (50mg/m2 d1-d3) and Etoposide (100 mg/m2 d1-5) over a period of 10 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
complete remission (CR) rate	To assess the complete remission (CR) rate with the use of ADE chemotherapy in relapsed acute myeloid leukemia (AML) after first CR	Day 28 ± 7 of treatment or after recovery of blood counts whichever is earlier

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event free survival (EFS) and overall survival(OS)	To determineevent free survival(EFS) and overall survival(OS)	2 year
toxicity of chemotherapy	To assess the toxicity of chemotherapy using CTCAE 4.0	Day 28 ± 7 of treatment
clonal evolution	To evaluate clonal evolution using cytogenetics &RT-PCR panel	Day 28 ± 7 of treatment
minimal residual disease (MRD)	To assess minimal residual disease (MRD) by using flow cytometry	Day 28 ± 7 of treatment or after recovery of blood counts whichever is earlier
cardiac function	To evaluate cardiac function using 2 Dimensional Echocardiography	Day 28 ± 7 of treatment

Collaborators and Investigators

• Sponsor: All India Institute of Medical Sciences, New Delhi

Study record dates

Study Major Dates

• Study Start (Anticipated): February 15, 2017
• Primary Completion (Anticipated): December 31, 2019
• Study Completion (Anticipated): December 31, 2019

Study Registration Dates

• First Submitted: February 7, 2017
• First Submitted That Met QC Criteria: February 10, 2017
• First Posted (Actual): February 15, 2017

Study Record Updates

• Last Update Posted (Actual): February 15, 2017
• Last Update Submitted That Met QC Criteria: February 10, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Recurrence
• Other Study ID Numbers: IECPG-660/22.12.2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No