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

NCT00060424 | Completed Phase 2 Results DMC

• 4 other identifiers: 1711.00NCI-2010-01276NCI-2011-01116P30CA015704
• Study Type: interventional
• Target: 21
• Locations: 2 countries
• Sites: 3

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.

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

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Number of patients surviving 18 months post-transplant.

  At 18 months

Secondary Outcomes (4)

• Rate of Relapse

  18 months

• Acute Grade II-IV GVHD and Chronic (Extensive) GVHD

  aGVHD: 100 days after transplant; cGVHD: 1 Year after transplant.

• Rate and Types of Infections

  18 months

• Transplant-related Mortality

  At 200 days

Study Arms (1)

Treatment (enzyme inhibitor, transplant, GVHD prophylaxis)

EXPERIMENTAL

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: Cyclosporine; Drug: Fludarabine Phosphate; Procedure: Hematopoietic Cell Transplantation; Other: Laboratory Biomarker Analysis; Drug: Mycophenolate Mofetil; Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Radiation: Total-Body Irradiation

Interventions

Cyclosporine DRUG

Given PO

Also known as: 27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Neoral, OL 27-400, Sandimmun, Sandimmune, SangCya

Treatment (enzyme inhibitor, transplant, GVHD prophylaxis)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, Oforta, SH T 586

Treatment (enzyme inhibitor, transplant, GVHD prophylaxis)

Hematopoietic Cell Transplantation PROCEDURE

Undergo allogeneic peripheral blood stem cell transplant

Also known as: HCT, Hematopoietic Stem Cell Transplantation, HSCT, stem cell transplantation

Treatment (enzyme inhibitor, transplant, GVHD prophylaxis)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (enzyme inhibitor, transplant, GVHD prophylaxis)

Mycophenolate Mofetil DRUG

Given PO

Also known as: Cellcept, MMF

Treatment (enzyme inhibitor, transplant, GVHD prophylaxis)

Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic peripheral blood stem cell transplant

Also known as: Non-myeloablative allogeneic transplant, Nonmyeloablative Stem Cell Transplantation, NST

Treatment (enzyme inhibitor, transplant, GVHD prophylaxis)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: TOTAL BODY IRRADIATION, Whole-Body Irradiation

Treatment (enzyme inhibitor, transplant, GVHD prophylaxis)

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Veterans Administration Center-Seattle

Seattle, Washington, 98108, United States

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

University of Torino

Torino, 10126, Italy

Location

Related Publications (1)

• 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.

  PMID: 32499241 DERIVED

MeSH Terms

Conditions

Leukemia, Prolymphocytic, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Leukemia, Prolymphocytic, T-Cell

Interventions

Cyclosporine; Cyclosporins; fludarabine phosphate; Stem Cell Transplantation; Hematopoietic Stem Cell Transplantation; Mycophenolic Acid; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, T-Cell

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Radiotherapy; Investigative Techniques

Results Point of Contact

• Title: David G Maloney, MD PhD
• Organization: Fred Hutch

dmaloney@fredhutch.org

Study Officials

• David Maloney

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 6, 2003
• First Posted: May 7, 2003
• Study Start: March 1, 2003
• Primary Completion: September 1, 2010
• Study Completion: September 22, 2010
• Last Updated: December 8, 2017
• Results First Posted: December 8, 2017

Record last verified: 2017-12

Locations

IT (1); US (2)