A Phase I Study to Examine the Toxicity of Allogeneic Stem Cell Transplantation for Relapsed or Therapy Refractory Ewing Sarcoma

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to examine the toxicity of using allogeneic stem cell transplantation for treatment of subjects with relapsed or refractory Ewing Sarcoma (ES). Donors will consist of either Human Leukocyte Antigen identical (HLA)or 9/10 (A, B, C, DR, DQ [A, B, C, are Class I markers for HLA and DR and DQ are Class II markers for Matching for Transplant for Donors to match with recipient]) matched related or unrelated donors. Specifically, we will examine: The toxicity of allogeneic stem cell transplant (SCT) in this patient population, as related to incidence of grade 3-4 acute Graft Verse Host Disease (GVHD). The incidence of transplant related mortality at 100 days.

Official Title
-----------------
A Phase I Study to Examine the Toxicity of Allogeneic Stem Cell Transplantation for Relapsed or Therapy Refractory Ewing Sarcoma

Conditions
-----------------
Ewing Sarcoma

Intervention / Treatment
-----------------
* Biological: allogeneic stem cell transplantation
* Drug: Clyclophosphamide
* Drug: Fludarabina
* Drug: Busulfan
* Drug: Melphalan


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients aged 0-30 years with relapsed or therapy refractory Ewings sarcoma, excluding patients with brain metastases. Patients who have received a prior autologous stem cell transplant are eligible. Related and unrelated marrow and peripheral blood stem donors must be 9/10 or 10/10 (HLA A, B, C, DR, DQ) matched with the recipient. Exclusion Criteria: Organ dysfunction: Patients who have the following levels of organ system dysfunction are not eligible: Cardiac: Ejection Fraction less than 50 percent Renal: Est. Creatinine Clearance less than 50 Hepatic: Bilirubin greater than 3.0 Pulmonary: Diffusing Capacity for Carbon Monoxide (DLCO) less than 70 percent, or for patient who cannot cooperate with pulmonary function testing, O2 saturation less than 95 percent on room air. Performance status: Lansky performance less than 70; Eastern Cooperative Oncology Group (ECOG) status greater than or equal to 2 Patients with an isolated recurrence of their tumor (in the site of primary tumor) greater than 1 year after completing therapy are excluded as these patients could be cured with local therapy alone. As part of the standard of care for pre-transplant evaluation subjects will be tested for exposure to viral agents such as hepatitis B, C, HTLV-1/2 and HIV. Subjects testing positive for HI may be rejected as candidates for transplantation, based on the clinical judgement of the stem cell transplant physician.

Ages Eligible for Study
-----------------
Maximum Age: 30 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 |
| --- | --- |
| Experimental: allogeneic stem cell transplantation Plan A<br>Subjects will receive the vaccine, Busulfan and Melphalan. | Biological: allogeneic stem cell transplantation<br> <br> Drug: Busulfan<br> <br> Drug: Melphalan<br> <br> |
| Experimental: allogeneic stem cell transplantation Plan B<br>If subject have already received a stem cell transplant using Busulfan and Melphalan, they will receive Clysophosohamide and Fludarabine. | Biological: allogeneic stem cell transplantation<br> <br> Drug: Clyclophosphamide<br> <br> Drug: Fludarabina<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of Grade 3-4 GVHD |  | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ewings sarcoma