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

Sponsored by:	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 Radiation Therapy

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

Show 23 Study Locations

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

Study placed in the following topic categories:

Antimetabolites
Leukemia, Lymphoid
Cyclosporine
Immunologic Factors
Lymphoma, Follicular
Folate
Cyclophosphamide
Tacrolimus
Follicular Lymphoma
Cyclosporins
Vitamin B9
Lymphoma, Small Cleaved-cell, Diffuse
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Antifungal Agents

Mycophenolate mofetil
Methotrexate
Leukemia, B-cell, Chronic
Alkylating Agents
Lymphoma
Immunoproliferative Disorders
Fludarabine monophosphate
Folinic Acid
Folic Acid Antagonists
Immunosuppressive Agents
Recurrence
Folic Acid
Lymphatic Diseases
Waldenstrom Macroglobulinemia
Chronic Lymphocytic Leukemia

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Leukemia, Lymphoid
Antimetabolites, Antineoplastic
Cyclosporine
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Reproductive Control Agents
Cyclophosphamide
Tacrolimus
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
Enzyme Inhibitors
Fludarabine monophosphate
Folic Acid Antagonists

ClinicalTrials.gov processed this record on July 02, 2009