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

October 22, 2015 updated by: Memorial Sloan Kettering Cancer Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 40 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Chemo followed by DSCT
  • 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.
Drug: thiotepa
Procedure: allogeneic bone marrow transplantation
Procedure: allogeneic hematopoietic stem cell transplantation
Drug: busulfan
Procedure: peripheral blood stem cell transplantation
Drug: melphalan
Biological: graft versus host disease prophylaxis/therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall Objective Response
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Susan Prockop, MD, Memorial Sloan Kettering Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2005

Primary Completion (Actual)

October 1, 2009

Study Completion (Actual)

October 1, 2009

Study Registration Dates

First Submitted

July 26, 2006

First Submitted That Met QC Criteria

July 26, 2006

First Posted (Estimate)

July 27, 2006

Study Record Updates

Last Update Posted (Estimate)

November 25, 2015

Last Update Submitted That Met QC Criteria

October 22, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 05-059
  • MSKCC-05059

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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