Comparison of Fludarabine Plus Total-Body Irradiation With Combination Chemotherapy Followed by Donor Peripheral Stem Cell Transplantation in Treating Patients With Relapsed Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia - Full Text View

Sponsor:	Simmons Cancer Center
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00041288

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor 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 or radiation therapy. Sometimes the transplanted cells are rejected by the body's normal tissues. Cyclosporine, mycophenolate mofetil, methotrexate, and tacrolimus may prevent this from happening.

PURPOSE: Randomized phase II trial to compare the effectiveness of fludarabine plus total-body irradiation with that of combination chemotherapy followed by donor peripheral stem cell transplantation in treating patients who have relapsed non-Hodgkin's lymphoma or chronic lymphocytic leukemia.

Condition	Intervention	Phase
Leukemia Lymphoma	Biological: therapeutic allogeneic lymphocytes Drug: cyclophosphamide Drug: cyclosporine Drug: fludarabine phosphate Drug: methotrexate Drug: mycophenolate mofetil Drug: tacrolimus Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	A Phase II Multicenter Randomized Study Of Two Non-Myeloablative Stem Cell Transplant Strategies For Low-Grade Lymphoma And CLL

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma

Drug Information available for: Cyclophosphamide Methotrexate Fludarabine Cyclosporine Fludarabine monophosphate Cyclosporin Tacrolimus anhydrous Tacrolimus Mycophenolate mofetil hydrochloride Mycophenolate Mofetil

U.S. FDA Resources

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

Study Start Date:

October 2001

Detailed Description:

OBJECTIVES:

Compare the 1-year overall survival rate of patients with relapsed low-grade non-Hodgkin's lymphoma or chronic lymphocytic leukemia treated with fludarabine and total body irradiation vs cyclophosphamide and fludarabine followed by allogeneic peripheral blood stem cell transplantation and donor lymphocyte infusions.
Compare the toxic effects of these regimens in these patients.
Compare the incidence and severity of acute and chronic graft-versus-host disease in patients treated with these regimens.
Compare the 1-year treatment-related mortality and infectious complications in patients treated with these regimens.
Compare the efficacy of these treatment regimens, in terms of 1-year disease-free survival, of these patients.
Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease, age (less than 55 vs over 55), and participating transplantation center. Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive fludarabine IV on days -4 to -2. Patients undergo total body irradiation followed by allogeneic peripheral blood stem cell transplantation (PBSCT) on day 0. Patients receive graft-versus-host disease (GVHD) prophylaxis comprising oral cyclosporine twice daily on days -2 to 90 followed by a taper on days 90-150 and oral mycophenolate mofetil twice daily on days 0-28.
Arm II: Patients receive fludarabine IV on days -6 to -2 and cyclophosphamide IV on days -3 to -2. Patients undergo PBSCT on day 0. Patients receive GVHD prophylaxis comprising methotrexate IV on days 1, 3, 6, and 11 and tacrolimus IV continuously and then orally on days -2 to 90 followed by a taper on days 90-150.

At approximately day 180, patients with persistent disease, evidence of T-cell chimerism, and no GVHD may receive up to 3 donor lymphocyte infusions administered every 1-2 months.

Quality of life is assessed at baseline, 1 month, every 3 months for 1 year, and then every 6 months for 1 year.

Patients are followed at 1 month, every 3 months for 1 year, and then annually for 2 years.

PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of chronic lymphocytic leukemia OR
Diagnosis of non-Hodgkin's lymphoma
- Lymphoplasmacytic lymphoma
- Grade I follicular small cleaved cell lymphoma
- Grade II follicular mixed cell lymphoma
- Diffuse small cleaved cell lymphoma
- Small lymphocytic lymphoma
Relapsed after at least 1 course of prior therapy
Availability of a 6/6 HLA A, B, and DR identical sibling donor
Nonmyeloablative transplantation candidate
No clinically significant effusions or ascites that would preclude administration of methotrexate

PATIENT CHARACTERISTICS:

Age:

18 to 75

Performance status:

ECOG 0-2 OR
Zubrod 0-2

Life expectancy:

At least 6 months

Hematopoietic:

Not specified

Hepatic:

Bilirubin no greater than 3 mg/dL

Renal:

Creatinine no greater than 2 mg/dL

Cardiovascular:

LVEF at least 40% on MUGA scan or echocardiogram

Pulmonary:

DLCO at least 50% of predicted

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No uncontrolled bacterial, viral, fungal, or parasitic infection
HIV1 and HIV2 negative
No other active malignancy except basal cell skin cancer
No recent history of drug or alcohol abuse
No other primary disease or comorbid illness that would severely limit life expectancy

PRIOR CONCURRENT THERAPY:

Biologic therapy:

See Disease Characteristics
Prior autologous bone marrow transplantation allowed if disease has progressed after transplantation
No entry on study as part of a tandem autologous transplantation followed by nonmyeloablative allograft protocol

Chemotherapy:

Not specified

Endocrine therapy:

Not specified

Radiotherapy:

Not specified

Surgery:

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00041288

Hide Study Locations

Locations

United States, Colorado
Rocky Mountain Cancer Centers
Denver, Colorado, United States, 80218
United States, Delaware
Delaware Clinical & Laboratory Physicians
Newark, Delaware, United States, 19713
United States, Florida
Florida Hospital Cancer Institute
Orlando, Florida, United States, 32804
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612-9497
United States, Georgia
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, United States, 30342-1601
United States, Iowa
Holden Comprehensive Cancer Center
Iowa City, Iowa, United States, 52242-1009
United States, Missouri
University of Missouri Kansas City School of Medicine
Kansas City, Missouri, United States, 64111
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
St. Joseph's Hospital and Medical Center
Paterson, New Jersey, United States, 07503
United States, New York
James P. Wilmot Cancer Center
Rochester, New York, United States, 14642
United States, Oregon
Oregon Cancer Institute
Portland, Oregon, United States, 97239
United States, Pennsylvania
Kimmel Cancer Center of Thomas Jefferson University - Philadelphia
Philadelphia, Pennsylvania, United States, 19107-5541
University of Pennsylvania Cancer Center
Philadelphia, Pennsylvania, United States, 19104-4283
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37212
United States, Texas
Simmons Cancer Center - Dallas
Dallas, Texas, United States, 75235-8590
Texas Transplant Institute
San Antonio, Texas, United States, 78229
United States, Virginia
Massey Cancer Center
Richmond, Virginia, United States, 23298-0037
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792
Canada, Ontario
Ottawa Regional Cancer Centre
Ottawa, Ontario, Canada, K1H 1C4
Princess Margaret Hospital
Toronto, Ontario, Canada, M4S 1KN
University of Toronto
Toronto, Ontario, Canada, M5S 1A8
Canada, Quebec
Hopital du Saint-Sacrament, Quebec
Quebec City, Quebec, Canada, G1S 4L8

Sponsors and Collaborators

Simmons Cancer Center

Investigators

Study Chair:

Robert H. Collins, MD

Simmons Cancer 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

Study ID Numbers:	CDR0000069462, UTSMC-0501228, AMGEN-UTSMC-0501228, IBMTR-SC-00-02.1, ROCHE-UTSMC-0501228, SPRI-UTSMC-0501228, NCI-V02-1706
Study First Received:	July 8, 2002
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00041288 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

Waldenstrom macroglobulinemia
refractory chronic lymphocytic leukemia
recurrent grade 1 follicular lymphoma

recurrent grade 2 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent small lymphocytic lymphoma

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Leukemia, Lymphoid
Vidarabine
Antimetabolites, Antineoplastic
Cyclosporine
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Mycophenolic Acid
Reproductive Control Agents
Cyclophosphamide
Tacrolimus
Antibiotics, Antineoplastic

Cyclosporins
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Antifungal Agents
Therapeutic Uses
Abortifacient Agents
Mycophenolate mofetil
Methotrexate
Dermatologic Agents
Alkylating Agents
Lymphoma
Nucleic Acid Synthesis Inhibitors
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases

ClinicalTrials.gov processed this record on November 27, 2009