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

Lymphoma Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00041288
• Other study ID #: CDR0000069462
• Secondary ID: UTSMC-0501228AMG
• Status: Terminated
• Phase: Phase 2
• Start date: October 2001
• Est. completion date: January 2003

Study information

• Verified date: April 2020
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: January 2003
• Est. primary completion date: January 2003
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• therapeutic allogeneic lymphocytes

Drug:
• cyclophosphamide

• cyclosporine

• fludarabine phosphate

• methotrexate

• mycophenolate mofetil

• tacrolimus

Procedure:
• peripheral blood stem cell transplantation

Radiation:
• radiation therapy

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center

Countries where clinical trial is conducted

United States,  Canada,