Alemtuzumab, Fludarabine Phosphate, and Total-Body Irradiation Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer
Condition: Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia
MeSH terms: Burkitt Lymphoma; Mycoses; Lymphoma; Leukemia; Leukemia, Myeloid; Multiple Myeloma; Leukemia, Myeloid, Acute; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Hodgkin Disease; Lymphoma, Mantle-Cell; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, B-Cell, Marginal Zone; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Immunoblastic; Plasmablastic Lymphoma; Mycosis Fungoides; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Sezary Syndrome; Leukemia, T-Cell; Lymphoma, T-Cell, Cutaneous; Waldenstrom Macroglobulinemia; Leukemia-Lymphoma, Adult T-Cell; Leukemia, Myelomonocytic, Juvenile; Lymphoma, Large-Cell, Anaplastic; Leukemia, Hairy Cell; Leukemia, Myeloid, Chronic-Phase; Lymphomatoid Granulomatosis; Lymphoma, Extranodal NK-T-Cell; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Intraocular Lymphoma; Leukemia, Mast-Cell; Myelodysplastic Syndromes; Myeloproliferative Disorders; Immunoblastic Lymphadenopathy; Myelodysplastic-Myeloproliferative Diseases; Syndrome; Recurrence
Intervention: alemtuzumab; total-body irradiation; fludarabine phosphate; cyclosporine; mycophenolate mofetil; allogeneic hematopoietic stem cell transplantation; peripheral blood stem cell transplantation; graft versus host disease prophylaxis/therapy; laboratory biomarker analysis
Intervention description: Given IV; Undergo low-dose TBI; Given IV; Given PO or IV; Given PO; Undergo allogeneic stem cell transplantation; Undergo PBSCT; Undergo GVHD prophylaxis/therapy; Correlative studies
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Antineoplastic Agents, Immunological; Alemtuzumab; Fludarabine; Fludarabine phosphate; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Cyclosporins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Maximum age: 74 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying the side effects and best dose of alemtuzumab when given
      together with fludarabine phosphate and total-body irradiation followed by cyclosporine and
      mycophenolate mofetil in treating patients who are undergoing a donor stem cell transplant
      for hematologic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate, a
      monoclonal antibody, such as alemtuzumab, and radiation therapy before a donor stem cell
      transplant helps stop the growth of cancer cells. Giving chemotherapy or radiation therapy
      before or after transplant also stops the patient's immune system from rejecting the donor's
      bone marrow 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 after the transplant may stop this from
      happening.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The patient must be not eligible for conventional transplants and must have disease
             expected to be stable for at least 100 days without chemotherapy

          -  Patients with hematologic malignancies treatable with HCT will be included:

               -  Aggressive non-Hodgkin lymphomas (NHLs) and other histologies such as diffuse
                  large B-cell NHL: not eligible for autologous HCT, not eligible for conventional
                  myeloablative HCT, or after failed autologous HCT;

               -  Low grade NHL: with < 6 month duration of complete response (CR) between courses
                  of conventional therapy;

               -  Mantle cell NHL: may be treated in first CR;

               -  Chronic lymphocytic leukemia (CLL): must have failed 2 lines of conventional
                  therapy and must be refractory to fludarabine; this includes patients who fail to
                  have a complete or partial response after therapy with a regimen containing
                  fludarabine (or another nucleoside analog] or experience disease relapse within
                  12 months after completing therapy with a regimen containing fludarabine [or
                  another nucleoside analog);

               -  Hodgkin's disease (HD): must have received and failed frontline therapy and have
                  failed or were not eligible for autologous transplant;

               -  Multiple myeloma (MM): must have received prior chemotherapy or failed
                  autografting; following a planned autologous transplant [tandem] is allowed;

               -  Acute myeloid leukemia (AML): must have < 5% marrow blasts at the time of
                  transplant;

               -  Acute lymphocytic leukemia (ALL): must have < 5% marrow blasts at the time of
                  transplant;

               -  Chronic myelogenous leukemia (CML): patients will be accepted beyond first
                  clinical progression (CP1) if they have received previous myelosuppressive
                  chemotherapy or HCT, and have < 5% marrow blasts at time of transplant;

               -  Myelodysplastic syndrome/myeloproliferative disease (MDS/MPD): must have failed
                  previous myelosuppressive chemotherapy or HCT, and have < 5% marrow blasts at
                  time of transplant;

               -  Waldenstrom's macroglobulinemia: must have failed 2 courses of therapy

          -  Patient refuses to be treated on a conventional transplant protocol; for this
             inclusion criteria, transplants must be approved by both the participating
             institution's patient review committee, such as the Patient Care Conference (PCC) at
             the Fred Hutchinson Cancer Research Center (FHCRC), and the FHCRC principal
             investigator

          -  Patient with related or unrelated donors for whom:

               -  There is a likelihood of disease progression while HLA typing and results of a
                  preliminary search and the donor pool suggest that a 10/10 HLA-A, B, C, DRB1 and
                  DQB1 matched unrelated donor will not be found;

               -  Patient and donor must be matched for at least one DRB1 allele and one DQB1
                  allele;

               -  Best available matches are HLA class I HLA-A, -B, -C allele matched donors
                  allowing for any one or two DRB1 and/or DQB1 antigen/allele mismatch;

               -  There is no indication for an autologous transplantation as a treatment option

          -  DONOR: For HLA matching inclusion criteria, see patient inclusion criteria

          -  DONOR: Only peripheral blood stem cells (PBSC) will be permitted as a HSC source on
             this protocol

        Exclusion Criteria:

          -  Positive crossmatch between donor and recipients

          -  Patient's life expectancy is severely limited by diseases other than malignancy

          -  Patient has central nervous system (CNS) involvement with disease refractory to
             intrathecal chemotherapy

          -  Presence of circulating leukemic blasts (in the peripheral blood) detected by standard
             pathology for patients with AML, ALL or CML

          -  Patient is a fertile man or woman unwilling to use contraceptives during and for up to
             12 months post treatment

          -  Patient is a female who is pregnant or breastfeeding

          -  Patient is human immunodeficiency virus (HIV) positive

          -  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

          -  Patient has a fungal infection with radiological progression after receipt of
             amphotericin B or active triazole for greater than 1 month

          -  Patient has the following organ dysfunction:

               -  Symptomatic coronary artery disease or ejection fraction < 35% or other cardiac
                  failure requiring therapy; ejection fraction is required if age > 50 years or if
                  the patient has a history of anthracyclines or history of cardiac disease;

               -  Diffusion capacity of the lung for carbon monoxide (DLCO) < 35% total lung
                  capacity (TLC) < 35%, forced expiratory volume of the lung in one second (FEV1) <
                  35% and/or receiving supplementary continuous oxygen; the FHCRC study principal
                  investigator (PI) must approve enrollment of all patients with pulmonary nodules;

               -  Liver function abnormalities: patient with clinical or laboratory evidence of
                  liver disease will be evaluated for the cause of liver disease, its clinical
                  severity in terms of liver function, bridging fibrosis, and the degree of portal
                  hypertension; the patient will be excluded if he/she is 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

          -  Patient has poorly controlled hypertension and on multiple antihypertensives

          -  Karnofsky performance score < 70 for adult patients

          -  Lansky play-performance score < 70 for pediatric patients

          -  Patient received cytotoxic agents for "cytoreduction" within three weeks (or the
             interval in which a cycle of standard chemotherapy would be administered in a
             non-transplant setting) prior to initiating the nonmyeloablative transplant
             conditioning; (exceptions are hydroxyurea and imatinib mesylate)

          -  DONOR: Marrow donors

          -  DONOR: Positive crossmatch between donor and recipient

          -  DONOR: Donor is HIV-positive and/or has a medical condition that would result in
             increased risk for filgrastim (G-CSF) mobilization and harvest of PBSC

          -  DONOR: Donor age < 12 years