Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia
Condition: 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
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Leukemia, Prolymphocytic, T-Cell; Leukemia, Prolymphocytic, B-Cell; Recurrence
Intervention: Cyclosporine; Fludarabine Phosphate; Hematopoietic Cell Transplantation; Laboratory Biomarker Analysis; Mycophenolate Mofetil; Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Total-Body Irradiation
Intervention description: Given PO; Given IV; Undergo allogeneic peripheral blood stem cell transplant; Correlative studies; Given PO; Undergo allogeneic peripheral blood stem cell transplant; Undergo TBI
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Fludarabine; Fludarabine phosphate; Cyclosporins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: No

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.
    

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