Stem Cell Transplant for Juvenile Myelomonocytic Leukemia (JMML)

Study Overview
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Brief Summary
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The investigators hypothesize that long-term disease-free survival (DFS) in patients with JMML can be achieved with a treatment of busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by hematopoietic cell transplantation (HCT).

Detailed Description
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Prior to transplantation, subjects will receive BUSULFAN via the central venous line, six times a day for four days, CYCLOPHOSPHAMIDE via the central venous line once a day for two days, and MELPHALAN via the central venous line for one day. Busulfan, cyclophosphamide, and melphalan are given to destroy the subject's leukemia. As well, these drugs will destroy the subject's own immune system to help ensure the new bone marrow takes and grows after transplantation. On the day of transplantation, bone marrow or umbilical cord blood from the donor will arrive to the bone marrow transplant unit and be transfused via venous line. These new cells will replace the subject's bone marrow.

Official Title
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Hematopoietic Cell Transplantation in Children With Juvenile Myelomonocytic Leukemia

Conditions
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Juvenile Myelomonocytic Leukemia

Intervention / Treatment
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* Biological: Stem Cell Transplant
* Drug: Preparative Regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a diagnosis of JMML and fulfill these minimal criteria (International diagnostic criteria for JMML): Leukocytosis (> 13,000) with absolute monocytosis (> 1,000) The presence of immature myeloid cells in the peripheral blood Less than 30% marrow blasts Absence of t(9:22) or BCR-ABL transcript Adequate major organ function including: Cardiac: ejection fraction > 45% Hepatic: no clinical evidence of hepatic failure (e.g. coagulopathy, ascites) Karnofsky performance status > 70% or Lansky score > 50% Creatinine must be < 2 x normal for age Written informed consent. Exclusion Criteria: Active uncontrolled infection within one week of HCT.

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: Intent-to-Treat<br>Patients receiving study regimen. | Biological: Stem Cell Transplant<br>* Transplantation on Day 0.<br>* Other names: Bone marrow transplantation;Drug: Preparative Regimen<br>* Busulfan Cyclophosphamide Mesna Melphalan Anti-thymocyte Globulin (ATG)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine Probability of Long-term Disease Free Survival in JMML |  | at 1 year after transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined Incidence of Neutrophil Engraftment, Graft-versus-host Disease (GVHD), Regimen-related Toxicity, and Relapse. | Measured by AGVHD Grades 2 - 4. | at 1 year after transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stem cell transplant, long term survival, retinoic acid