Autologous Bone Marrow Transplant for Children With Acute Myelogenous Leukemia (AML) in First Complete Remission

Study Overview
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Brief Summary
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This study proposes to transfer marker genes (detectable genetic traits or segments of DNA that can be identified and tracked) into aliquots of marrow obtained for Bone Marrow Transplant (BTM) in patients in remission of Acute Myelogenous Leukemia (AML).

Detailed Description
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The primary objective of this study was to estimate the continuous complete remission rate at 2 years post transplant for children with AML in first complete remission treated with autologous BMT. Secondary objectives used transduction of marker genes into autologous marrow to determine the following: whether the source of relapse after BMT for AML is residual malignant cells in the harvested marrow or in the patient, and whether marrow purging is therefore rational. whether the majority of AML, which lack genetic markers, represent abnormalities in a multi-lineage progenitor cell, and whether therefore, auto grafting/intensified chemotherapy is ever likely to augment the cure rate. the mechanisms of autologous reconstitution, and the effects of stimuli which modify the process.

Official Title
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Autologous Bone Marrow Transplant for Children With AML in First Complete Remission: Use of Marker Genes to Investigate the Biology of Marrow Reconstitution and the Mechanism of Relapse

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Busulfan
* Drug: Cyclophosphamide
* Drug: Mesna


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged between 1 and 18 years at diagnosis with acute nonlymphocytic leukemia in first remission are eligible for this protocol. Patients enrolled on the AML-87 study in second or subsequent remission are eligible for this protocol. Exclusion Criteria: Has an HLA-matched, MLC-compatible donor(unless parents and/or patient refuses transplant. Diagnosis of FAB M3 or FAB M3v (acute progranulocytic leukemia) Life expectancy limited by disease other than leukemia Significant cardiac disease (echo shortening fraction <25% or MUGA scan <50%) Severe renal dysfunction, i.e., creatinine clearance less than 60cc/1.73 m2/min Severe restrictive pulmonary disease (FCV less than 40% of predicted) Severe hepatic disease (bilirubin greater than 3 mg/dl or SGPT greater than 500IU) Severe personality disorder or mental illness Previous severe cystitis from cyclophosphamide Previous total dose of anthracyclines of >450 mg/m2 Sever infection that on evaluation by the PI precludes ablative chemotherapy or successful transplantation Previous autologous transplant HIV reactivity Karnofsky score <70%

Ages Eligible for Study
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Minimum Age: 1 Year
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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1<br> | Drug: Busulfan<br>* See Detailed Description section for description of treatment plan.<br>* Other names: Myleran;Drug: Cyclophosphamide<br>* See Detailed Description section for description of treatment plan.<br>* Other names: Cytoxan, CTX;Drug: Mesna<br>* See Detailed Description section for description of treatment plan.<br>* Other names: MESNCX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To estimate the continuous complete remission rate at 2 years for children with AML in first complete remission treated with Autologous Bone Marrow Transplant (ABMT). |  | 2 years post transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autologous bone marrow transplant, gene marking