Study Of Two Non-Myeloablative Stem Cell Transplant Strategies For Low-Grade Lymphoma And CLL

Sponsor

University of Texas Southwestern Medical Center (Other)

Overall Status

Terminated

CT.gov ID

NCT00041288

Collaborator

(none)

Enrollment

Locations

Duration (Months)

0.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	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 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

A Phase II Multicenter Randomized Study Of Two Non-Myeloablative Stem Cell Transplant Strategies For Low-Grade Lymphoma And Chronic Lymphocytic Leukemia (CLL)

Study Start Date :

Oct 1, 2001

Actual Primary Completion Date :

Jan 1, 2003

Actual Study Completion Date :

Jan 1, 2003

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 human leukocyte antigen (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:

Eastern Cooperative Oncology Group (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: left ventricular ejection fraction (LVEF) at least 40% on multigated acquisition (MUGA) scan or echocardiogram
Pulmonary: diffusing capacity of lung for carbon monoxide (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
Human Immunodeficiency Virus (HIV)1 and Human Immunodeficiency Virus (HIV)2 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
Biologic therapy:Prior autologous bone marrow transplantation allowed if disease has progressed after transplantation
Biologic therapy: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

Locations

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