Clinical trial NCT00041288: Study Of Two Non-Myeloablative Stem Cell Transplant Strategies For Low-Grade Lymphoma And CLL
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Leukemia
Lymphoma
Keywords: 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
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2003-01-27
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

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 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 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Newark
country: United States
facility: Delaware Clinical & Laboratory Physicians
state: Delaware
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Atlanta
country: United States
facility: Blood and Marrow Transplant Group of Georgia
state: Georgia
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center
state: Iowa
city: Kansas City
country: United States
facility: University of Missouri Kansas City School of Medicine
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Paterson
country: United States
facility: St. Joseph's Hospital and Medical Center
state: New Jersey
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center
state: New York
city: Portland
country: United States
facility: Oregon Cancer Institute
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center of Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: Simmons Cancer Center - Dallas
state: Texas
city: San Antonio
country: United States
facility: Texas Transplant Institute
state: Texas
city: Richmond
country: United States
facility: Massey Cancer Center
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Ottawa
country: Canada
facility: Ottawa Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Toronto
country: Canada
facility: University of Toronto
state: Ontario
city: Quebec City
country: Canada
facility: Hopital du Saint-Sacrament, Quebec
state: Quebec
Study officials:
affiliation: Simmons Cancer Center
name: Robert H. Collins, MD
role: STUDY_CHAIR
References: