Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
The Leukemia and Lymphoma Society
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00060424
First received: May 6, 2003
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

This clinical trial studies how well giving fludarabine phosphate together with total-body irradiation (TBI) before donor peripheral blood stem cell transplant works in treating patients with chronic lymphocytic leukemia or small lymphocytic leukemia. Giving low doses of chemotherapy, such as fludarabine phosphate, and TBI before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. Giving chemotherapy before or after peripheral blood stem cell transplant also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before and after the transplant may stop this from happening.


Condition Intervention Phase
B-cell Chronic Lymphocytic Leukemia
Contiguous Stage II Small Lymphocytic Lymphoma
Noncontiguous Stage II Small Lymphocytic Lymphoma
Prolymphocytic Leukemia
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Stage I Chronic Lymphocytic Leukemia
Stage I Small Lymphocytic Lymphoma
Stage II Chronic Lymphocytic Leukemia
Stage III Chronic Lymphocytic Leukemia
Stage III Small Lymphocytic Lymphoma
Stage IV Chronic Lymphocytic Leukemia
Stage IV Small Lymphocytic Lymphoma
Drug: fludarabine phosphate
Drug: cyclosporine
Drug: mycophenolate mofetil
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Procedure: hematopoietic stem cell transplantation
Radiation: total-body irradiation
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Hematopoietic Stem Cell Transplantation With Nonmyeloablative Conditioning for Patients With Chronic Lymphocytic Leukemia - a Multi-Center Trial

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Survival using a non-myeloablative conditioning regimen with HSCT in patients with fludarabine phosphate-refractory CLL [ Time Frame: At 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Acute grade II-IV GVHD and chronic GVHD [ Time Frame: At day 84 ] [ Designated as safety issue: No ]
  • Transplant-related mortality [ Time Frame: At 200 days ] [ Designated as safety issue: No ]
    Defined as death before day +200 not related to progression of disease.


Estimated Enrollment: 40
Study Start Date: March 2003
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (enzyme inhibitor, transplant, GVHD prophylaxis)
NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and TBI on day 0. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine PO every 12 hours on days -3 to 180 with taper on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27.
Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Drug: cyclosporine
Given PO
Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
Drug: mycophenolate mofetil
Given PO
Other Names:
  • Cellcept
  • MMF
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Undergo allogeneic peripheral blood stem cell transplant
Procedure: hematopoietic stem cell transplantation
Undergo allogeneic peripheral blood stem cell transplant
Other Name: Stem Cell Transplantation
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine whether nonmyeloablative allogeneic hematopoietic stem cell transplantation (HSCT) from matched-related donors can improve the probability of survival 18 months after treatment for fludarabine (fludarabine phosphate)-refractory, fludarabine phosphate, cyclophosphamide, and rituximab (FCR)-failed, or del 17p chronic lymphocytic leukemia (CLL) beyond that observed in historical controls (30%).

SECONDARY OBJECTIVES:

I. To assess the rate of relapse with allogeneic HSCT using nonmyeloablative conditioning for patients with fludarabine-refractory, FCR-failed, or del 17p CLL compared with historical data on autologous HSCT.

II. To estimate the incidence of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD in patients with CLL treated with low-dose TBI, fludarabine, PBSC infusion and immunosuppression with cyclosporine and mycophenolatemofetil.

III. To characterize the rate and types of infections with this regimen.

IV. To estimate the rate of transplant-related mortality in the first 200 days.

OUTLINE:

NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and TBI on day 0.

TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0.

GVHD PROPHYLAXIS: Patients receive cyclosporine orally (PO) every 12 hours on days -3 to 180 with taper beginning on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27.

After completion of study treatment, patients are followed up at 12 and 18 months and then annually for 5 years.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with CLL (or small lymphocytic lymphoma) or diagnosis of CLL that progresses to prolymphocytic leukemia (PLL), or T-cell CLL or PLL
  • Patients with B-Cell CLL or PLL who have at least one of the following:
  • Failed to meet National Cancer Institute (NCI) Working Group criteria for complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog, e.g. cladribine [2-CDA], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing fludarabine (or another nucleoside analog)
  • Failed FCR combination chemotherapy at any time point
  • Had de novo of acquired "17p deletion" cytogenetic abnormality; patients should have received induction chemotherapy but could be transplanted in 1st complete response (CR)
  • Patient has a suitable human leukocyte antigen (HLA)-matched related donor who is willing to undergo leukapheresis initially for collection of peripheral blood stem cells (PBSC) and subsequently for collection of peripheral blood mononuclear cells (PBMC) with filgrastim (G-CSF) mobilization and willing to donate stem cells
  • DONOR: Related donor who is HLA phenotypically or genotypically identical at the allele level at HLA-A, -B, -C, -DRB1, and -DQB1
  • DONOR: Donor must consent to G-CSF administration and leukapheresis
  • DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian)

Exclusion Criteria:

  • Infection with human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV)-1, or HTLV-2
  • Active central nervous system (CNS) involvement with CLL
  • Patients with active non-hematologic malignancies (except non-melanoma skin cancers)
  • Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence
  • Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
  • Pregnant or breastfeeding women
  • Karnofsky score =< 70
  • Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
  • Cytotoxic agents for "cytoreduction" (with the exception of imatinib mesylate [Gleevec], cytokine therapy, hydroxyurea, chlorambucil or rituxan) within three weeks of the initiation of conditioning
  • Active bacterial or fungal infections unresponsive to medical therapy
  • Cardiovascular: cardiac ejection fraction < 40%; patients with poorly controlled hypertension despite multiple antihypertensives
  • Pulmonary: diffusing capacity of carbon monoxide (DLCO) < 40%, total lung capacity (TLC) < 40%, forced expiratory volume in one second (FEV1) < 40% and/or requiring continuous supplementary oxygen, or severe deficits in pulmonary function testing as defined by pulmonary consultant service
  • Liver function abnormalities: patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dL, or symptomatic biliary disease
  • DONOR: Age < 12 years
  • DONOR: Identical twin
  • DONOR: Pregnancy
  • DONOR: Infection with HIV
  • DONOR: Inability to achieve adequate venous access
  • DONOR: Known allergy to filgrastim (G-CSF)
  • DONOR: Current serious systemic illness
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00060424

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Veterans Administration Center-Seattle
Seattle, Washington, United States, 98108
Italy
University of Torino
Torino, Italy, 10126
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
The Leukemia and Lymphoma Society
Investigators
Principal Investigator: David Maloney Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00060424     History of Changes
Other Study ID Numbers: 1711.00, NCI-2010-01276, NCI-2011-01116, 1711.00, P30CA015704
Study First Received: May 6, 2003
Last Updated: May 22, 2014
Health Authority: United States: Federal Government

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

ClinicalTrials.gov processed this record on July 23, 2014