Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: Giving low doses of chemotherapy, such as fludarabine phosphate, and total-body irradiation 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.

PURPOSE: This clinical trial studies how well giving fludarabine phosphate together with total-body irradiation before donor peripheral blood stem cell transplant works in treating patients with chronic lymphocytic leukemia or small lymphocytic leukemia.

Further Study Information

PRIMARY OBJECTIVES:

I. To determine whether nonmyeloablative allogeneic HSCT from matched-related donors can improve the probability of survival 18 months after treatment for fludarabine-refractory, FCR-failed, or del 17p 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 GVHD and chronic GVHD in patients with CLL treated with low-dose TBI, fludarabine, PBSC infusion and immunosuppression with cyclosporine and mycophenylate mofetil.

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 IV on days -4 to -2 and total-body irradiation on day 0.

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

GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: Patients receive oral cyclosporine every 12 hours on days -3 to 180 with taper on day 56 and oral mycophenolate mofetil every 12 hours on days 0-27.

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

Eligibility Criteria

Inclusion

• 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 has at least one of the following:

• Failed to meet NCI Working Group criteria for complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog, e.g. 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 CR

• Patient has a suitable HLA-matched related donor who is willing to undergo leukapheresis initially for collection of PBSC and subsequently for collection of PBMC with 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

Exclusion

• Infection with HIV, HTLV-1, or HTLV-2

• Active 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 Gleevac, 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: DLCO < 40%, TLC <40%, 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

Trial Contact Information

Trial Lead Organizations/Sponsors

Fred Hutchinson Cancer Research Center

David Maloney

Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00060424
Information obtained from ClinicalTrials.gov on January 30, 2012

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