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Busulfan, Melphalan, and Thiotepa Followed By a Donor Stem Cell Transplant in Treating Patients With High-Risk Ewing's Tumors

Primary Purpose

Sarcoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
graft versus host disease prophylaxis/therapy
busulfan
melphalan
thiotepa
allogeneic bone marrow transplantation
allogeneic hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sarcoma focused on measuring metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor, recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor

Eligibility Criteria

undefined - 40 Years (Child, Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Diagnosis of high-risk tumors of the Ewing's family as defined by 1 of the following: Biopsy-proven disease with distant metastases to sites other than the lung Relapsed disease after completion of prior standard front-line therapy or high-dose chemotherapy Currently in complete remission (CR) with no evidence of disease (with or without minimal residual disease) or very good partial remission (i.e., CR with an abnormal bone scan) after prior standard or high-dose chemotherapy with local control HLA-compatible stem cell donor available Compatible donors include those matched at both HLA-A, -B, -C, -DR and 1 of 2 -DQ alleles by high-resolution molecular typing Related or unrelated donor PATIENT CHARACTERISTICS: Karnofsky performance status (PS) 70-100% (≥ 16 years old) OR Lansky PS 70-100% (< 16 years old) LVEF > 50% at rest SGOT < 3 times upper limit of normal Bilirubin < 2.0 mg/dL (unless liver is involved with disease) Creatinine normal AND/OR creatinine clearance > 60 mL/min Lung diffusion capacity > 50% of predicted (corrected for hemoglobin) OR asymptomatic with a room air oxygen saturation of ≥ 98% Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active uncontrolled viral, bacterial, or fungal infection No HIV-1 or -2 positivity PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior therapy with 100 mg/m² of melphalan No prior high-dose chemotherapy requiring autologous stem cell rescue No prior radiotherapy to > 50% of the pelvic marrow space

Sites / Locations

  • Memorial Sloan-Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Chemo followed by DSCT

Arm Description

Myeloablative preparative regimen: Patients receive busulfan IV over 2 hours every 6 hours on days -8 to -6, melphalan IV over 20 minutes on days -5 to -3, and thiotepa IV over 4 hours on day -2. Allogeneic hematopoietic stem cell transplant: Patients undergo allogeneic bone marrow or T-cell depleted peripheral blood stem cell transplantation on day 0. Graft-vs-host disease (GVHD) prophylaxis: Patients receive treatment according to institutional guidelines and are given treatment against infection. After completion of study treatment, patients are followed periodically for at least 3 years.

Outcomes

Primary Outcome Measures

Overall Objective Response

Secondary Outcome Measures

Full Information

First Posted
July 26, 2006
Last Updated
October 22, 2015
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00357396
Brief Title
Busulfan, Melphalan, and Thiotepa Followed By a Donor Stem Cell Transplant in Treating Patients With High-Risk Ewing's Tumors
Official Title
A Phase II Trial of a Chemotherapy Based Regimen of Intravenous Busulfan (Busulfex), Melphalan and Thiotepa as Myeloablative Regimen Followed by a T- Cell Depleted Allogeneic Hematopoietic Stem Cell Transplant From and HLA-Compatible Donor in the Treatment of High Risk Ewing's Sarcoma Family Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
October 2015
Overall Recruitment Status
Completed
Study Start Date
June 2005 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
October 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
RATIONALE: Giving chemotherapy drugs, such as busulfan, melphalan, and thiotepa, before a donor stem cell transplant helps stop the growth of tumor cells and prepares the patient's bone marrow for the stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal tissues. Giving tacrolimus, sirolimus, and mycophenolate mofetil may stop this from happening. PURPOSE: This phase II trial is studying how well giving busulfan together with melphalan and thiotepa followed by a donor stem cell transplant works in treating patients with high-risk Ewing's tumors.
Detailed Description
OBJECTIVES: Evaluate disease-free and overall survival of patients with high-risk tumors of the Ewing's family treated with unmodified T-cell depleted allogeneic hematopoietic stem cell transplantation after cytoreduction comprising busulfan, melphalan, and thiotepa. Determine the regimen-related morbidity and mortality in these patients. Determine the incidence of acute and chronic graft-vs-host disease in patients treated with this regimen. Determine the biologic response of minimal residual disease in patients treated with this regimen. OUTLINE: This is a prospective study. Myeloablative preparative regimen: Patients receive busulfan IV over 2 hours every 6 hours on days -8 to -6, melphalan IV over 20 minutes on days -5 to -3, and thiotepa IV over 4 hours on day -2. Allogeneic hematopoietic stem cell transplant: Patients undergo allogeneic bone marrow or T-cell depleted peripheral blood stem cell transplantation on day 0. Graft-vs-host disease (GVHD) prophylaxis: Patients receive treatment according to institutional guidelines and are given treatment against infection. After completion of study treatment, patients are followed periodically for at least 3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcoma
Keywords
metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor, recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Chemo followed by DSCT
Arm Type
Experimental
Arm Description
Myeloablative preparative regimen: Patients receive busulfan IV over 2 hours every 6 hours on days -8 to -6, melphalan IV over 20 minutes on days -5 to -3, and thiotepa IV over 4 hours on day -2. Allogeneic hematopoietic stem cell transplant: Patients undergo allogeneic bone marrow or T-cell depleted peripheral blood stem cell transplantation on day 0. Graft-vs-host disease (GVHD) prophylaxis: Patients receive treatment according to institutional guidelines and are given treatment against infection. After completion of study treatment, patients are followed periodically for at least 3 years.
Intervention Type
Biological
Intervention Name(s)
graft versus host disease prophylaxis/therapy
Intervention Type
Drug
Intervention Name(s)
busulfan
Intervention Type
Drug
Intervention Name(s)
melphalan
Intervention Type
Drug
Intervention Name(s)
thiotepa
Intervention Type
Procedure
Intervention Name(s)
allogeneic bone marrow transplantation
Intervention Type
Procedure
Intervention Name(s)
allogeneic hematopoietic stem cell transplantation
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Primary Outcome Measure Information:
Title
Overall Objective Response
Time Frame
2 years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of high-risk tumors of the Ewing's family as defined by 1 of the following: Biopsy-proven disease with distant metastases to sites other than the lung Relapsed disease after completion of prior standard front-line therapy or high-dose chemotherapy Currently in complete remission (CR) with no evidence of disease (with or without minimal residual disease) or very good partial remission (i.e., CR with an abnormal bone scan) after prior standard or high-dose chemotherapy with local control HLA-compatible stem cell donor available Compatible donors include those matched at both HLA-A, -B, -C, -DR and 1 of 2 -DQ alleles by high-resolution molecular typing Related or unrelated donor PATIENT CHARACTERISTICS: Karnofsky performance status (PS) 70-100% (≥ 16 years old) OR Lansky PS 70-100% (< 16 years old) LVEF > 50% at rest SGOT < 3 times upper limit of normal Bilirubin < 2.0 mg/dL (unless liver is involved with disease) Creatinine normal AND/OR creatinine clearance > 60 mL/min Lung diffusion capacity > 50% of predicted (corrected for hemoglobin) OR asymptomatic with a room air oxygen saturation of ≥ 98% Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active uncontrolled viral, bacterial, or fungal infection No HIV-1 or -2 positivity PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior therapy with 100 mg/m² of melphalan No prior high-dose chemotherapy requiring autologous stem cell rescue No prior radiotherapy to > 50% of the pelvic marrow space
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susan Prockop, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Busulfan, Melphalan, and Thiotepa Followed By a Donor Stem Cell Transplant in Treating Patients With High-Risk Ewing's Tumors

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