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

NCT ID: NCT00060424

Last Updated: 2017-12-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-03-31
• Study Completion Date: 2010-09-22

Brief Summary

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.

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, peripheral blood stem cell (PBSC) infusion and immunosuppression with cyclosporine and mycophenolate 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 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.

Conditions

B-Cell Prolymphocytic Leukemia; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Cyclosporine

Intervention Type: DRUG

Given PO

Fludarabine Phosphate

Intervention Type: DRUG

Given IV

Hematopoietic Cell Transplantation

Intervention Type: PROCEDURE

Undergo allogeneic peripheral blood stem cell transplant

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Mycophenolate Mofetil

Intervention Type: DRUG

Given PO

Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation

Intervention Type: PROCEDURE

Undergo allogeneic peripheral blood stem cell transplant

Total-Body Irradiation

Intervention Type: RADIATION

Undergo TBI

Interventions

Cyclosporine

Given PO

Intervention Type: DRUG

Fludarabine Phosphate

Given IV

Intervention Type: DRUG

Hematopoietic Cell Transplantation

Undergo allogeneic peripheral blood stem cell transplant

Intervention Type: PROCEDURE

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Mycophenolate Mofetil

Given PO

Intervention Type: DRUG

Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation

Undergo allogeneic peripheral blood stem cell transplant

Intervention Type: PROCEDURE

Total-Body Irradiation

Undergo TBI

Intervention Type: RADIATION

Other Intervention Names

27-400; Ciclosporin; CsA; Cyclosporin; Cyclosporin A; Neoral; OL 27-400; Sandimmun; Sandimmune; SangCya; 2-F-ara-AMP; 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-; Beneflur; Fludara; Oforta; SH T 586; HCT; Hematopoietic Stem Cell Transplantation; HSCT; stem cell transplantation; Cellcept; MMF; Non-myeloablative allogeneic transplant; Nonmyeloablative Stem Cell Transplantation; NST; TOTAL BODY IRRADIATION; Whole-Body Irradiation

Eligibility 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 first (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 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

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

David Maloney

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David Maloney

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Locations

Veterans Administration Center-Seattle

Seattle, Washington, United States

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States

University of Torino

Torino, , Italy

Countries

Germany; United States; Italy

References

Cooper JP, Storer BE, Granot N, Gyurkocza B, Sorror ML, Chauncey TR, Shizuru J, Franke GN, Maris MB, Boyer M, Bruno B, Sahebi F, Langston AA, Hari P, Agura ED, Lykke Petersen S, Maziarz RT, Bethge W, Asch J, Gutman JA, Olesen G, Yeager AM, Hubel K, Hogan WJ, Maloney DG, Mielcarek M, Martin PJ, Flowers MED, Georges GE, Woolfrey AE, Deeg JH, Scott BL, McDonald GB, Storb R, Sandmaier BM. Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades. Haematologica. 2021 Jun 1;106(6):1599-1607. doi: 10.3324/haematol.2020.248187.

Reference Type: DERIVED

PMID: 32499241 (View on PubMed)

Other Identifiers

NCI-2010-01276

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2011-01116

Identifier Type: -

Identifier Source: secondary_id

1711.00

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA015704

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1711.00

Identifier Type: -

Identifier Source: org_study_id