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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00357396
First received: July 26, 2006
Last updated: March 15, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Sarcoma
Biological: graft versus host disease prophylaxis/therapy
Drug: busulfan
Drug: melphalan
Drug: thiotepa
Procedure: allogeneic bone marrow transplantation
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Disease-free survival at 1 year [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Morbidity and mortality [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Incidence of acute and chronic graft-vs-host disease (GVHD) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Biologic response of minimal residual disease [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: June 2005
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Biological: graft versus host disease prophylaxis/therapy Drug: busulfan Drug: melphalan Drug: thiotepa Procedure: allogeneic bone marrow transplantation Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation

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.

  Eligibility

Ages Eligible for Study:   up to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00357396

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Study Chair: Susan Prockop, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00357396     History of Changes
Other Study ID Numbers: 05-059, MSKCC-05059
Study First Received: July 26, 2006
Last Updated: March 15, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor
recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor

Additional relevant MeSH terms:
Sarcoma, Ewing's
Neuroectodermal Tumors, Primitive, Peripheral
Sarcoma
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Busulfan
Melphalan
Thiotepa
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists

ClinicalTrials.gov processed this record on April 21, 2014