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

Study Overview
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Brief Summary
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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 A retrospective analysis (unpublished) conducted at IRCH, AIIMS on relapsed AML patients treated with ADE (Cytarabine, Daunorubicin and Etoposide) chemotherapy showed the CR rates of approximately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.

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

Conditions
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Acute Myeloid Leukemia, in Relapse

Intervention / Treatment
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* Drug: ADE Protocol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Either gender with age ≤18 years at initial diagnosis AML(non-M3) patients at first relapse (medullary) Exclusion Criteria: Primary refractory AML &secondary AML More than or equal to 2 relapses of AML Symptomatic cardiac dysfunction (CTCAE Grade 3 or 4) Active infection(pneumonia etc.) Any other organ dysfunction (CTCAE Grade 4) Patients not willing to consent for the study

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADE arm<br>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<br>* 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<br>|

What is the study measuring?
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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 |