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Immunosuppression With Mycophenolate Mofetil and Cyclosporine in Preventing Graft-Versus-Host Disease in Patients Undergoing Donor Peripheral Stem Cell Transplantation for Hematologic Malignancies or Metastatic Renal Cell Carcinoma
This study is ongoing, but not recruiting participants.

First Received on March 8, 2004.   Last Updated on November 16, 2011   History of Changes
Sponsor: Fred Hutchinson Cancer Research Center
Collaborator: National Cancer Institute (NCI)
Information provided by: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00078858
  Purpose

RATIONALE: Giving different schedules of mycophenolate mofetil and cyclosporine may be effective in reducing graft-versus-host disease in patients undergoing donor peripheral stem cell transplantation for hematologic malignancies (cancer) and metastatic renal cell carcinoma.

PURPOSE: This phase I/II trial is studying the side effects and best way to give mycophenolate mofetil and cyclosporine and to see how well they work in reducing graft-versus-host disease in treating patients who are undergoing donor peripheral stem cell transplantation for hematologic cancer or metastatic renal cell carcinoma.


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Graft Versus Host Disease
Kidney Cancer
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Biological: graft-versus-tumor induction therapy
Drug: cyclosporine
Drug: fludarabine phosphate
Drug: mycophenolate mofetil
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
Phase I
Phase II

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Prolonged Mycophenolate Mofetil And Truncated Cyclosporine Postgrafting Immunosuppression To Reduce Life-Threatening GVHD After Unrelated Donor Peripheral Blood Cell Transplantation Using Nonmyeloablative Conditioning For Patients With Hematologic Malignancies And Renal Cell Carcinoma - A Multi-Center Trial

Resource links provided by NLM:


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

Study Start Date: September 2003
Primary Completion Date: January 2006 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine whether the incidence of life-threatening graft-versus-host disease (GVHD) can be reduced after unrelated donor peripheral blood mononuclear cell hematopoietic stem cell transplantation using nonmyeloablative conditioning with truncated cyclosporine and prolonged administration of mycophenolate mofetil in patients with hematologic malignancies or metastatic renal cell carcinoma.

Secondary

  • Compare the incidence of acute and chronic GVHD in patients treated with this regimen vs patients treated on protocols FHCRC-1463.00 and FHCRC-1641.00.
  • Compare the utilization of corticosteroids in patients treated with this regimen vs patients treated on protocols FHCRC-1463.00 and FHCRC-1641.00.
  • Compare the survival of patients treated with this regimen vs patients treated on protocols FHCRC-1463.00 and FHCRC-1641.00.

OUTLINE: This is a multicenter study.

  • Conditioning regimen: Patients receive fludarabine IV over 30 minutes on days -4 to -2 and low-dose total body irradiation (TBI) on day 0.
  • Allogeneic hematopoietic stem cell transplantation (HSCT): After the completion of TBI, patients undergo allogeneic HSCT on day 0.
  • Immunosuppression: Patients receive oral cyclosporine twice daily on days -3 to 80 in the absence of acute graft-versus-host disease (GVHD). Patients also receive oral mycophenolate mofetil (MMF) 3 times daily on days 0-29 and then, in the absence of GVHD, twice daily on days 30-149. MMF is tapered beginning on day 150 and continuing until day 180.

Patients are followed at 6 months, 12 months, 18 months, and 24 months and then annually for 5 years after HSCT.

PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study within 1.5 years.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of either of the following:

    • Hematologic malignancy

      • Meeting 1 of the following criteria:

        • Over 50 years of age with a hematologic malignancy treatable by unrelated hematopoietic stem cell transplantation (HSCT) = 50 years of age and under with a hematologic malignancy treatable by allogeneic HSCT and considered to be at high risk for regimen-related toxicity associated with a conventional transplantation (greater than 40% risk of transplant-related mortality) due to a preexisting medical condition or prior therapy OR refused a conventional HSCT
      • Including, but not limited to the following:

        • Intermediate- or high-grade non-Hodgkin's lymphoma (NHL)

          • Not eligible for autologous HSCT or failed autologous HSCT
        • Low-grade NHL

          • Less than 6 months duration of complete remission (CR) between courses of conventional therapy
        • Chronic lymphocytic leukemia

          • Refractory to fludarabine
        • Hodgkin's lymphoma

          • Failed prior front-line therapy
        • Multiple myeloma

          • Received prior chemotherapy (consolidation of chemotherapy by autografting prior to nonmyeloablative HSCT is allowed)
        • Acute myeloid leukemia (AML)

          • Less than 5% marrow blasts at the time of transplantation
        • Acute lymphoblastic leukemia

          • Less than 5% marrow blasts at the time of transplantation
        • Chronic myelogenous leukemia (CML)

          • Chronic phase or accelerated phase
          • Prior autografts after high-dose therapy OR prior intensive chemotherapy with filgrastim (G-CSF)-mobilized peripheral blood mononuclear cell autologous or conventional HSCT for advanced CML allowed provided disease is in CR or chronic phase and there are less than 5% marrow blasts at the time of transplantation
        • Myelodysplastic syndromes (MDS) or myeloproliferative disorder

          • Refractory anemia (RA)
          • RA with ringed sideroblasts
          • Patients with greater than 5% marrow blasts (including those with transformation to AML) must receive cytotoxic chemotherapy and achieve less than 5% marrow blasts at the time of transplantation
    • Metastatic renal cell carcinoma (RCC) not amenable to surgical cure OR history of or active histologically or radiologically confirmed metastatic disease, including 1 of the following histological types:

      • Clear cell
      • Papillary
      • Medullary
  • No rapidly progressive intermediate- or high-grade NHL
  • No history of brain metastases (RCC patients)
  • No CNS involvement with disease refractory to intrathecal chemotherapy
  • No other non-hematological tumors except RCC
  • Available unrelated donor

    • Matched for HLA-A, B, C, DRB1, and DQB1
    • Only a single allele disparity is allowed for HLA-A, B, or C
    • No positive anti-donor cytotoxic crossmatch
    • No patient and donor pairs homozygous at a mismatched allele in the graft rejection vector
    • No marrow donors NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age

  • See Disease Characteristics
  • Any age

Performance status

  • Karnofsky 60-100% (70-100% for RCC patients)

Life expectancy

  • At least 6 months (RCC patients)

Hematopoietic

  • Not specified

Hepatic

  • No fulminant liver failure
  • No cirrhosis of the liver with evidence of portal hypertension
  • No alcoholic hepatitis
  • No hepatic encephalopathy
  • No uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the PT
  • No ascites related to portal hypertension
  • No bacterial or fungal liver abscess
  • No biliary obstruction
  • No chronic viral hepatitis with bilirubin greater than 3 mg/dL
  • No symptomatic biliary disease
  • No esophageal varices
  • No history of bleeding esophageal varices

Renal

  • Not specified

Cardiovascular

  • Cardiac ejection fraction at least 35%*
  • No hypertension greater than grade II NOTE: *Ejection fraction required for patients with a history of anthracycline exposure or cardiac disease

Pulmonary

  • DLCO at least 40%
  • No requirement for continuous supplementary oxygen
  • Pulmonary nodules allowed provided study enrollment is approved by the principal investigator

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for 1 year after study participation
  • HIV negative
  • No fungal infection with radiological progression after prior amphotericin B or active triazole therapy for more than 1 month
  • No vertebral instability (RCC patients)

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Disease Characteristics
  • Prior cytokine therapy allowed
  • Prior rituximab allowed
  • No concurrent growth factors for 1 month after HSCT

Chemotherapy

  • See Disease Characteristics
  • More than 2 weeks since prior intensive chemotherapy, excluding low-dose cytarabine and chlorambucil

Endocrine therapy

  • Not specified

Radiotherapy

  • Prior radiotherapy for advanced malignancy or to reduce tumor bulk allowed

Surgery

  • Not specified

Other

  • More than 2 weeks since prior cytotoxic agents for cytoreduction, excluding hydroxyurea and imatinib mesylate
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00078858

Locations
United States, California
Stanford Cancer Center at Stanford University Medical Center
Stanford, California, United States, 94305-5623
United States, Colorado
Rocky Mountain Cancer Centers - Denver Midtown
Denver, Colorado, United States, 80218
United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, Oregon
Cancer Institute at Oregon Health and Science University
Portland, Oregon, United States, 97239-3098
United States, Utah
Huntsman Cancer Institute at University of Utah
Salt Lake City, Utah, United States, 84112
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
United States, Wisconsin
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, United States, 53226
Germany
Universitaet Leipzig
Leipzig, Germany, D-04103
Universitaetsklinikum Tuebingen
Tuebingen, Germany, D-72076
Italy
Azienda Sanitaria Ospedale San Giovanni Battista Molinette di Torino
Turin, Italy, 10126
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Study Chair: Brenda Sandmaier, MD Fred Hutchinson Cancer Research Center
  More Information

Additional Information:
No publications provided

Responsible Party: Brenda Sandmaier, MD, FHCRC
ClinicalTrials.gov Identifier: NCT00078858     History of Changes
Other Study ID Numbers: 1668.00, FHCRC-1668.00, CDR0000346473
Study First Received: March 8, 2004
Last Updated: November 16, 2011
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:
graft versus host disease
recurrent renal cell cancer
stage IV renal cell cancer
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent childhood large cell lymphoma
recurrent childhood lymphoblastic lymphoma
recurrent childhood small noncleaved cell lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
refractory anemia with ringed sideroblasts
polycythemia vera
essential thrombocythemia
recurrent/refractory childhood Hodgkin lymphoma
refractory multiple myeloma
adult acute lymphoblastic leukemia in remission
adult acute myeloid leukemia in remission
untreated adult acute lymphoblastic leukemia
untreated adult acute myeloid leukemia
untreated childhood acute lymphoblastic leukemia
untreated childhood acute myeloid leukemia and other myeloid malignancies
refractory chronic lymphocytic leukemia
clear cell renal cell carcinoma

Additional relevant MeSH terms:
Neoplasms
Carcinoma
Carcinoma, Renal Cell
Kidney Neoplasms
Graft vs Host Disease
Leukemia
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Hematologic Neoplasms
Myelodysplastic-Myeloproliferative Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Immune System Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on February 09, 2012