Chemotherapy, Radiation Therapy, Peripheral Stem Cell Transplantation, and Immunosuppressive Therapy in Treating Patients With Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00006251
First received: September 11, 2000
Last updated: August 20, 2010
Last verified: August 2010
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy. Sometimes the transplanted cells are rejected by the body's normal tissues. Immunosuppressive drugs such as mycophenolate mofetil and cyclosporine may be an effective treatment to prevent rejection.

PURPOSE: Phase I/II trial to study the effectiveness of combining chemotherapy, radiation therapy, and peripheral stem cell transplantation followed by immunosuppressive therapy in treating patients who have cancer.


Condition Intervention Phase
Cancer
Biological: therapeutic allogeneic lymphocytes
Drug: chemotherapy
Drug: cyclosporine
Drug: fludarabine phosphate
Drug: mycophenolate mofetil
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Induction of Mixed Hematopoietic Chimerism in Patients Using Fludarabine, Low Dose TBI, PBSC Infusion and Post-Transplant Immunosuppression With Cyclosporine and Mycophenolate Mofetil

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Study Start Date: May 2000
Study Completion Date: September 2005
Primary Completion Date: September 2005 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES: I. Determine the risk of graft rejection associated with the addition of fludarabine to a nonmyeloablative conditioning regimen in patients with malignancies treatable by allogeneic bone marrow (stem cell) transplantation. II. Compare the rate of graft rejection in patients treated with this regimen vs patients previously untreated with fludarabine. III. Determine the rate of acute grade II/IV graft versus host disease (GVHD) and chronic GVHD in these patients treated with fludarabine, low dose total body irradiation, and allogeneic peripheral blood stem cell transplantation followed by immunosuppression with cyclosporine and mycophenolate mofetil.

OUTLINE: This is a multicenter study. Patients receive fludarabine IV on days -4 to -2, and total body irradiation followed by filgrastim (G-CSF) mobilized allogeneic peripheral blood stem cell transplantation on day 0. Patients also receive oral cyclosporine twice daily on days -3 to 56 and oral mycophenolate mofetil twice daily on days 0 to 27. Following completion of immunosuppression therapy patients with stable mixed chimerism and no evidence of graft versus host disease (GVHD) receive donor lymphocytes IV over 30 minutes on or after day 65. Treatment repeats every 65 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed weekly until day 90 after last lymphocyte infusion, at 4, 6, 12, 18, and 24 months, and then annually thereafter.

PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study within 2 years.

  Eligibility

Ages Eligible for Study:   up to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS: 50 to 74 years old and diagnosed with non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), or multiple myeloma Not eligible for curative autologous transplantation or failed prior autologous transplantation NHL and CLL patients must have failed prior therapy with an alkylating agent and/or fludarabine or be at high risk for relapse Multiple myeloma patients must have stage II or III disease and received prior chemotherapy OR Under 50 years old and diagnosed with NHL, CLL, or multiple myeloma Not eligible for curative autologous transplantation At high risk for regimen related toxicity due to prior autologous transplantation or preexisting medical condition OR Under 75 years old and diagnosed with other malignant disease treatable by allogeneic bone marrow transplantation Not eligible for curative autologous transplantation At high risk for toxicity related to standard high dose regimens due to a preexisting chronic disease affecting kidneys, liver, lungs, and heart Includes the following likely diseases: Myelodysplastic syndrome Myeloproliferative syndromes Acute leukemia with less than 10% blasts Amyloidosis Hodgkin's disease Renal cell carcinoma OR Other malignancies for which patient has declined standard allografts No rapidly progressive aggressive NHL unless in minimal disease state No active CNS involvement Must have HLA genotypically or phenotypically identical related donor meeting these criteria: 12 to 74 years old (pediatric donors will provide bone marrow) No identical twin Not pregnant HIV negative No known allergy to filgrastim (G-CSF) No concurrent serious systemic illness Hormone receptor status: Not specified

PATIENT CHARACTERISTICS: Age: Under 75 Menopausal status: Not specified Performance status: Karnofsky 50-100% Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN) SGPT and SGOT under 4 times ULN Renal: Renal failure allowed Cardiovascular: Cardiac ejection fraction at least 40% No poorly controlled hypertension Pulmonary: No severe defects in pulmonary function No supplementary continuous oxygen Other: Not pregnant or nursing Fertile patients must use effective contraception during and for 1 year following study HIV negative

PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics No concurrent posttransplantation colony stimulating factors during mycophenolate mofetil Chemotherapy: See Disease Characteristics Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00006251

Locations
United States, California
Beckman Research Institute, City of Hope
Los Angeles, California, United States, 91010
Stanford University
Stanford, California, United States, 94305
United States, Colorado
University of Colorado Cancer Center
Denver, Colorado, United States, 80262
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
Germany
Universitaet Leipzig - Chirurgische Klinik und Poliklinik I
Leipzig, Germany, D-04103
Italy
University of Torino
Torino, Italy, 10126
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Study Chair: David G. Maloney, MD, PhD Fred Hutchinson Cancer Research Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00006251     History of Changes
Other Study ID Numbers: 1533.00, FHCRC-1533.00, NCI-H00-0062, CDR0000068184
Study First Received: September 11, 2000
Last Updated: August 20, 2010
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Fred Hutchinson Cancer Research Center:
stage III breast cancer
stage IV breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
recurrent childhood acute lymphoblastic leukemia
recurrent adult Hodgkin lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
refractory multiple myeloma
recurrent childhood rhabdomyosarcoma
stage IV renal cell cancer
recurrent renal cell cancer
stage II ovarian epithelial cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
recurrent ovarian epithelial cancer
disseminated neuroblastoma
recurrent neuroblastoma
recurrent Wilms tumor and other childhood kidney tumors
stage II multiple myeloma
stage III multiple myeloma
recurrent childhood lymphoblastic lymphoma
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
recurrent childhood acute myeloid leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
stage III malignant testicular germ cell tumor
recurrent malignant testicular germ cell tumor

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma, Large-Cell, Immunoblastic
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclosporins
Cyclosporine
Mycophenolic Acid
Mycophenolate mofetil
Fludarabine monophosphate
Vidarabine
Fludarabine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antimetabolites, Antineoplastic

ClinicalTrials.gov processed this record on May 23, 2013