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

Sponsored by:	Memorial Sloan-Kettering Cancer Center
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00357396

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

MedlinePlus related topics: Bone Marrow Transplantation Cancer Soft Tissue Sarcoma

Drug Information available for: Melphalan Thiotepa Melphalan hydrochloride Sarcolysin Busulfan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

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

Estimated Enrollment:	30
Study Start Date:	June 2005
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

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.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

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	Recruiting
New York, New York, United States, 10021
Contact: Susan Prockop, MD 212-639-6715

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

Investigators

Study Chair:

Susan Prockop, MD

Memorial Sloan-Kettering Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Responsible Party:	Memorial Sloan-Kettering Cancer Center ( Susan Prockop )
Study ID Numbers:	CDR0000487592, MSKCC-05059
Study First Received:	July 26, 2006
Last Updated:	December 16, 2008
ClinicalTrials.gov Identifier:	NCT00357396
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor
recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor

Study placed in the following topic categories:

Melphalan
Neuroectodermal Tumors, Primitive
Malignant mesenchymal tumor
Ewing's family of tumors
Osteosarcoma
Osteogenic sarcoma
Recurrence
Soft tissue sarcomas
Thiotepa

Neuroectodermal Tumors
Neoplasms, Connective and Soft Tissue
Sarcoma, Ewing's
Ewing's sarcoma
Peripheral neuroectodermal tumor
Busulfan
Sarcoma
Neuroepithelioma
Neuroectodermal Tumors, Primitive, Peripheral

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions

Neoplasms
Neoplasms, Bone Tissue
Therapeutic Uses
Myeloablative Agonists
Neoplasms, Connective Tissue
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009