Donor Stem Cell Transplant in Treating Young Patients With Relapsed or Refractory Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: A peripheral stem cell, bone marrow, or umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving busulfan and melphalan with or without antithymocyte globulin before transplant and cyclosporine with methylprednisolone or methotrexate after transplant may stop this from happening. PURPOSE: This phase I trial is studying the side effects of donor stem cell transplant in treating young patients with relapsed or refractory solid tumors.

Detailed Description
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OBJECTIVES: Determine the toxicity of allogeneic hematopoietic stem cell transplantation, in terms of the incidence of grade 3-4 acute graft-versus-host disease, in young patients with relapsed or refractory solid tumors. Determine the incidence of transplant-related mortality at 100 days post-transplantation in these patients. OUTLINE: Conditioning: Patients receive busulfan IV or orally 4 times daily on days -8 to -5 (a total of 16 doses) and melphalan IV over 15-20 minutes on days -4 to -2. Patients with an unrelated donor also receive anti-thymocyte globulin IV on days -4 to -2. Allogeneic hematopoietic stem cell transplantation (SCT): Patients undergo allogeneic hematopoietic SCT on day 0. Post-transplant graft-versus-host disease (GVHD) prophylaxis: Patients who undergo cord blood SCT receive cyclosporine and methylprednisolone for graft-versus-host disease (GVHD) prophylaxis. Patients who undergo peripheral blood or bone marrow SCT receive cyclosporine and methotrexate (short course) for GVHD prophylaxis. After completion of study treatment, patients are followed at 1, 3, 6, and 12 months and then annually thereafter. PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study within 4 years.

Official Title
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A Phase I Study to Examine the Toxicity of Allogeneic Stem Cell Transplantation for Pediatric Solid Tumors With Relapsed or Therapy Refractory Disease

Conditions
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Neuroblastoma, Sarcoma, Unspecified Childhood Solid Tumor, Protocol Specific

Intervention / Treatment
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* Biological: anti-thymocyte globulin
* Drug: busulfan
* Drug: cyclosporine
* Drug: melphalan
* Drug: methotrexate
* Drug: methylprednisolone
* Procedure: allogeneic bone marrow transplantation
* Procedure: peripheral blood stem cell transplantation
* Procedure: umbilical cord blood transplantation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of relapsed or refractory solid tumor, including, but not limited to, relapsed neuroblastoma, relapsed Ewing's sarcoma, and relapsed rhabdomyosarcoma No isolated local disease recurrence at the site of the primary tumor > 1 year after completion of prior therapy No brain tumor or brain metastases Related or unrelated hematopoietic stem cell donor available, meeting 1 of the following criteria: Matched for HLA-A, -B, -C, -DR, and -DQ (9/10 or 10/10 allelles) (marrow or peripheral blood) Matched for HLA-A, -B, and -DR (5/6 or 6/6 allelles) (cord blood) Cord blood specimen must contain ≥ 2 x 10 ^7 nucleated cells/kg body weight PATIENT CHARACTERISTICS: Age 30 and under Performance status ECOG 0-1 OR Lansky 80-100% Life expectancy Not specified Hematopoietic Not specified Hepatic Bilirubin ≤ 3.0 mg/dL Renal Creatinine clearance ≥ 50 mL/min Cardiovascular Ejection fraction ≥ 50% Pulmonary DLCO ≥ 70% OR O_2 saturation ≥ 95% on room air Other Not pregnant Negative pregnancy test Fertile patients must use effective contraception HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy Prior autologous stem cell transplantation allowed Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified

Ages Eligible for Study
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Maximum Age: 30 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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: anti-thymocyte globulin|nan|
|Drug: busulfan|nan|
|Drug: cyclosporine|nan|
|Drug: melphalan|nan|
|Drug: methotrexate|nan|
|Drug: methylprednisolone|nan|
|Procedure: allogeneic bone marrow transplantation|nan|
|Procedure: peripheral blood stem cell transplantation|nan|
|Procedure: umbilical cord blood transplantation|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified childhood solid tumor, protocol specific, recurrent neuroblastoma, recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor, recurrent childhood rhabdomyosarcoma