Total-Body Irradiation and Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Hematologic Cancer or Kidney Cancer - Full Text View

Sponsor:	Fred Hutchinson Cancer Research Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:	NCT00027820

Purpose

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

PURPOSE: Phase I/II trial to study the effectiveness of total-body irradiation and chemotherapy followed by peripheral stem cell transplantation in treating patients who have hematologic cancer or kidney cancer.

Condition	Intervention	Phase
Chronic Myeloproliferative Disorders Kidney Cancer Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Biological: therapeutic allogeneic lymphocytes 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: Treatment
Official Title:	Low-Dose TBI and Fludarabine Followed by Nonmyeloablative Unrelated Donor Peripheral Blood Stem Cell Transplantation Using Enhanced Postgrafting Immunosuppression for Patients With Hematologic Malignancies and Renal Cell Carcinoma - A Multi-Center Trial

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia essential thrombocythemia hemophilia polycythemia vera

MedlinePlus related topics: Acute Lymphocytic Leukemia Acute Myeloid Leukemia Anemia Cancer Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Kidney Cancer Leukemia Lymphoma Multiple Myeloma Myelodysplastic Syndromes

Drug Information available for: Fludarabine Cyclosporine Fludarabine monophosphate Cyclosporin Mycophenolate mofetil hydrochloride Mycophenolate Mofetil

U.S. FDA Resources

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

Study Start Date:	August 2001
Primary Completion Date:	December 2003 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine whether stable unrelated peripheral blood stem cell grafts can be safely established using fludarabine, total-body irradiation, and peripheral blood stem cell transplantation with enhanced post-grafting immunosuppression comprising mycophenolate mofetil and cyclosporine in patients with hematologic malignancies or renal cell carcinoma.
Determine whether the incidence and severity of acute grades II-IV graft-versus-host disease can be reduced in patients with sustained engraftment when treated with mycophenolate mofetil every 8 hours.
Determine whether engraftment can be maintained in patients with low chimerism and high risk of rejection with a single dose of fludarabine followed by donor lymphocyte infusion while on continued mycophenolate mofetil and cyclosporine.
Compare disease-free and overall survival in patients treated with this regimen to those treated on protocol FHCRC-1463.00.

OUTLINE: This is a multicenter study.

Cytoreduction: Patients with advanced malignancies may receive cytoreduction and/or radiotherapy at the discretion of the attending physician and protocol chairperson.
Conditioning: Patients receive fludarabine IV on days -4 to -2. Patients undergo low-dose total-body irradiation followed by allogeneic peripheral blood stem cell (PBSC) transplantation on day 0.
Immunosuppression (graft-vs-host disease prophylaxis): Patients receive oral cyclosporine (CSP) twice daily on days -3 to 100 and then tapered to day 177. Patients also receive oral mycophenolate mofetil (MMF) every 8 hours beginning on day 0 (4-6 hours after PBSC transplantation), continuing to day 40, and then tapered off by day 96.
Donor lymphocyte infusion (DLI): Patients are evaluated for lymphoid and myeloid chimerism on days 28, 56, and 84. Patients without disease progression presenting with low-donor T-cell chimerism (less than 40%), no evidence of graft-versus-host disease requiring therapy, and no active infection revert CSP and MMF doses to their original strength (if tapering has begun) and receive fludarabine IV on day -2 (of DLI). Patients receive DLI on day 0. MMF is continued for 28 days and tapered for 28 days. CSP is continued during MMF therapy and then tapered over 3 months.

Patients are followed weekly until day 90, at 4, 6, 12, 18, and 24 months, and then annually thereafter.

PROJECTED ACCRUAL: A maximum of 150 patients will be accrued for this study within 2 years.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed metastatic renal cell carcinoma not amenable to surgical cure
- Clear cell, papillary, or medullary
- No other solid tumors OR
Histologically proven hematologic malignancy including, but not limited to, the following:
- Intermediate or high-grade non-Hodgkin's lymphoma (NHL)
  - Ineligible for autologous hematopoietic stem cell transplantation (HSCT) or failed prior autologous HSCT
- Low-grade NHL
  - Less than 6 months duration of complete remission between courses of conventional therapy
- Chronic lymphocytic leukemia
  - Failed 2 lines of conventional therapy and refractory to fludarabine
- Hodgkin's lymphoma
  - Failed front-line therapy
- Multiple myeloma
  - Prior chemotherapy required
  - Consolidation of chemotherapy by prior autografting allowed
- Acute myeloid leukemia (AML)
  - Less than 5% blasts at time of transplantation
- Acute lymphoblastic leukemia
  - Less than 5% blasts at time of transplantation
- Chronic myelogenous leukemia (CML)
  - Chronic or accelerated phase
  - Patients who have received autografts after high-dose therapy or have undergone intensive chemotherapy with autologous or conventional HSCT for advanced CML are allowed if in complete remission or chronic phase and have less than 5% blasts at time of transplantation
- Myelodysplastic syndromes (MDS) or myeloproliferative disorders (MPD)
  - Refractory anemia
  - Refractory anemia with ringed sideroblasts
  - Patients with MDS or MPD with transformation to AML must receive cytotoxic chemotherapy and achieve less than 5% blasts at time of transplantation
Over age 50:
- Hematologic malignancy treatable by unrelated HSCT
Age 50 and under:
- Hematologic disease treatable by allogenic HSCT who, through pre-existing medical conditions or prior therapy, are considered at high risk for regimen-related toxicity associated with or who refuse conventional transplantation
No rapidly progressive intermediate or high-grade NHL
No CNS involvement refractory to intrathecal chemotherapy
No history of brain metastases (for renal cell carcinoma patients)
Availability of unrelated donor
- Matched for HLA-DRB1 and DQB1 alleles AND
- Matched for all serologically recognized HLA-A or B or C antigens and at least 5 of 6 HLA-A or B or C alleles
- 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 renal cell carcinoma patients)

Life expectancy:

At least 6 months for renal cell carcinoma patients

Hematopoietic:

See Disease Characteristics

Hepatic:

No fulminant liver failure
No cirrhosis of the liver with portal hypertension
No alcoholic hepatitis
No esophageal varices
No history of bleeding esophageal varices
No hepatic encephalopathy
No uncorrectable hepatic synthetic dysfunction evidenced by prolonged 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

Renal:

Not specified

Cardiovascular:

No hypertension greater than grade II
Cardiac ejection fraction at least 35%
No cardiac failure requiring therapy

Pulmonary:

DLCO at least 40% and/or receiving supplemental continuous oxygen
Pulmonary nodules allowed at discretion of principal investigator

Other:

HIV negative
Not pregnant or nursing
Fertile patients must use effective contraception during and for 12 months after study participation
No fungal infections with radiologically confirmed progression after receipt of amphotericin B or active triazole for more than 1 month
No vertebral instability for renal cell carcinoma patients

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics

Chemotherapy

See Disease Characteristics
Prior hydroxyurea allowed

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Other

Prior imatinib mesylate allowed
No other cytoreductive cytotoxic agents within 2 weeks of initiation of conditioning

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00027820

Locations

United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
Stanford University Medical Center
Stanford, California, United States, 94305-5623
Stanford University
Stanford, California, United States, 94305
United States, Colorado
University of Colorado Cancer Center
Denver, Colorado, United States, 80010
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30322
United States, Oregon
Oregon Cancer Institute
Portland, Oregon, United States, 97239
United States, Texas
Baylor University Medical Center
Dallas, Texas, United States, 75246
United States, Utah
Huntsman Cancer Institute
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
Italy
University of Torino
Torino, Italy, 10126

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Michael B. Maris, MD

Fred Hutchinson Cancer Research Center

More Information

Additional Information:

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

No publications provided

ClinicalTrials.gov Identifier:	NCT00027820 History of Changes
Other Study ID Numbers:	1641.00, FHCRC-1641.00, NCI-H01-0081, CDR0000069076
Study First Received:	December 7, 2001
Last Updated:	September 20, 2010
Health Authority:	United States: Federal Government

Keywords provided by Fred Hutchinson Cancer Research Center:

recurrent adult Hodgkin lymphoma
refractory multiple myeloma
stage IV renal cell cancer
recurrent renal cell cancer
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
adult acute myeloid leukemia in remission
adult acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
childhood acute lymphoblastic leukemia in remission
clear cell renal cell carcinoma
recurrent/refractory childhood Hodgkin lymphoma
refractory anemia

refractory anemia with ringed sideroblasts
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III adult diffuse large cell lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV adult diffuse large cell lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent adult diffuse large cell lymphoma
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
stage III grade 3 follicular lymphoma
stage IV grade 3 follicular lymphoma

Additional relevant MeSH terms:

Neoplasms
Carcinoma, Renal Cell
Kidney Neoplasms
Leukemia
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Lymphoma, Large-Cell, Immunoblastic
Myelodysplastic-Myeloproliferative Diseases
Adenocarcinoma

Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on February 12, 2012