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 recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2003 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00041288
First received: July 8, 2002
Last updated: February 6, 2009
Last verified: March 2003
  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 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


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:
No publications provided

ClinicalTrials.gov Identifier: NCT00041288     History of Changes
Other 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
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

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Cyclosporins
Cyclosporine
Methotrexate
Mycophenolate mofetil
Fludarabine monophosphate
Tacrolimus
Fludarabine
Mycophenolic Acid
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 14, 2014