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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00041288
Recruitment Status : Unknown
Verified March 2003 by National Cancer Institute (NCI).
Recruitment status was:  Active, not recruiting
First Posted : January 27, 2003
Last Update Posted : February 9, 2009
Information provided by:
National Cancer Institute (NCI)

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:


  • 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 Type : Interventional  (Clinical Trial)
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 CLL
Study Start Date : October 2001

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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



  • 18 to 75

Performance status:

  • ECOG 0-2 OR
  • Zubrod 0-2

Life expectancy:

  • At least 6 months


  • Not specified


  • Bilirubin no greater than 3 mg/dL


  • Creatinine no greater than 2 mg/dL


  • LVEF at least 40% on MUGA scan or echocardiogram


  • DLCO at least 50% of predicted


  • 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


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


  • Not specified

Endocrine therapy:

  • Not specified


  • Not specified


  • Not specified

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00041288

  Show 23 Study Locations
Sponsors and Collaborators
Simmons Cancer Center
Study Chair: Robert H. Collins, MD Simmons Cancer Center Identifier: NCT00041288     History of Changes
Other Study ID Numbers: CDR0000069462
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: February 9, 2009
Last Verified: March 2003

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:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Fludarabine phosphate
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Abortifacient Agents, Nonsteroidal
Abortifacient Agents