Alemtuzumab, Fludarabine Phosphate, and Low-Dose Total Body Irradiation Before Donor Stem Cell Transplantation in Treating Patients With Hematological Malignancies
Condition: Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Peripheral T-cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Progressive Hairy Cell Leukemia, Initial Treatment; 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 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; Splenic Marginal Zone Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Childhood Anaplastic Large Cell Lymphoma; Stage I Childhood Large Cell Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage I Small Lymphocytic Lymphoma; Stage II Childhood Anaplastic Large Cell Lymphoma; Stage II Childhood Large Cell Lymphoma; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Mycosis Fungoides/Sezary Syndrome; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Childhood Anaplastic Large Cell Lymphoma; Stage III Childhood Large Cell Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Childhood Anaplastic Large Cell Lymphoma; Stage IV Childhood Large Cell Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Waldenström Macroglobulinemia
MeSH terms: Burkitt Lymphoma; Mycoses; Lymphoma; Leukemia; Leukemia, Myeloid; Multiple Myeloma; Leukemia, Myeloid, Acute; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; 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; Sezary Syndrome; Leukemia, T-Cell; Lymphoma, T-Cell, Cutaneous; Waldenstrom Macroglobulinemia; Leukemia-Lymphoma, Adult T-Cell; Lymphoma, Large-Cell, Anaplastic; Leukemia, Hairy Cell; Leukemia, Myeloid, Chronic-Phase; Lymphomatoid Granulomatosis; Lymphoma, Extranodal NK-T-Cell; Leukemia, Large Granular Lymphocytic; Myelodysplastic Syndromes; Myeloproliferative Disorders; Immunoblastic Lymphadenopathy; Myelodysplastic-Myeloproliferative Diseases; Syndrome; Recurrence
Intervention: alemtuzumab; fludarabine phosphate; total-body irradiation; allogeneic hematopoietic stem cell transplantation; peripheral blood stem cell transplantation; mycophenolate mofetil; cyclosporine
Intervention description: Given IV; Given IV; Undergo TBI; Undergo allogeneic HSCT; Undergo allogeneic peripheral blood stem cell transplantation; Given PO; Given IV or PO
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: 60.0
Sex: All
Maximum age: 74 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the side effects and the best dose of alemtuzumab when given
      together with fludarabine phosphate and low-dose total body irradiation (TBI) and how well it
      works before donor stem cell transplant in treating patients with hematological malignancies.
      Giving chemotherapy and low-dose TBI before a donor peripheral blood stem cell transplant
      helps stop the growth of cancer cells. It may also stop the patient's immune system from
      rejecting the donor's stem cells. Also, monoclonal antibodies, such as alemtuzumab, can find
      cancer cells and either kill them or deliver cancer-killing substances to them without
      harming normal cells. When the healthy stem cells from a donor are infused into the patient
      they may help the patient's bone marrow make stem cells, red blood cells, white blood cells,
      and platelets. Sometimes the transplanted cells from a donor can also make an immune response
      against the body's normal cells. Giving cyclosporine (CSP) and mycophenolate mofetil (MMF)
      after transplant may stop this from happening.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients 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 hematopoietic stem cell transplant (HSCT) or
             with a B cell malignancy except those treatable with autologous transplant will be
             included

          -  Aggressive non-Hodgkin lymphomas (NHLs) and Other Histologies Such as Diffuse large B
             cell NHL

               -  Patients with primary refractory or relapsed disease not eligible for an
                  autologous transplant

               -  Patients are eligible following an autologous transplant in remission or in
                  relapse

               -  Planned tandem transplant is allowed for patients at high risk of relapse

          -  Low grade NHL with < 6 months duration of complete remission (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 be refractory to fludarabine

          -  Hodgkin disease (HD) - Must have received and failed frontline therapy; patients must
             have had a prior autologous transplant or were not eligible for autologous transplant;
             planned tandem transplants are allowed for patients at high risk of relapse

          -  Multiple myeloma (MM) - Must have received prior chemotherapy and a prior autologous
             transplant, unless autologous transplant was not possible; planned tandem transplants
             are allowed for patients at high risk of relapse

          -  Acute myeloid leukemia (AML) - Must have < 5% marrow blasts at the time of transplant

          -  Acute lymphocytic leukemia (ALL) - Must have < 5% blasts at the time of transplant

          -  Chronic myeloid leukemia (CML) - Patients will be accepted beyond chronic phase 1
             (CP1) if they have received previous myelosuppressive chemotherapy or HSCT, and have <
             5% marrow blasts at time of transplant

          -  Myelodysplastic (MDS)/Myeloproliferative disorders - Must have failed previous
             myelosuppressive chemotherapy or HSCT, and have < 5% marrow blasts at time of
             transplant

          -  Waldenstrom's Macroglobulinemia - Must have failed 2 courses of therapy

          -  Patients < 12 years old must be approved by the Fred Hutchinson Cancer Research Center
             (FHCRC) principal investigator (PI)

          -  Patients who refuse 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 FHCRC and the FHCRC principal investigator

          -  Patients with related or unrelated donors for whom

               -  The best available match is a HLA class II DRB1 and DQB1 matched donor
                  incompatible for any single serologically detectable class I HLA-A, -B, -C
                  mismatch; one additional allele level class I mismatch is allowed OR any
                  combination of 2 allele level mismatches (if typed at the molecular level)

               -  There is a likelihood of rapid disease progression while HLA typing and results
                  of a preliminary search and the donor pool suggests that a 10/10 HLA-A, B, C,
                  DRB1 and DQB1 matched unrelated donor will not be found

               -  There is no HLA-A, -B or -C one locus allelic mismatched related donor available

               -  There is no indication for an autologous transplantation as a treatment option

          -  DONOR: Related or unrelated donors who are matched for HLA-DRB1 and DQB1 alleles (must
             be defined by high resolution typing), and who are mismatched for:

               -  Any single serologically detectable HLA-A or B or C antigen +/- 1 allele or

               -  Any combination of two HLA-A, -B, or -C alleles (if prospectively typed at
                  molecular level)

        Exclusion Criteria:

          -  Patients who are homozygous at the mismatched major histocompatibility complex (MHC)
             class I locus

          -  A positive cross-match exists between the donor and recipient

          -  Patients with rapidly progressive intermediate or high grade NHL

          -  Presence of circulating leukemic blasts (in the peripheral blood) detected by standard
             pathology for patients with AML, ALL or CML

          -  Life expectancy severely limited by diseases other than malignancy

          -  Central nervous system (CNS) involvement with disease refractory to intrathecal
             chemotherapy

          -  Fertile men or women unwilling to use contraceptives during and for up to 12 months
             post treatment

          -  Female patients who are pregnant or breast-feeding

          -  Human immunodeficiency virus (HIV) positive patients

          -  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

          -  Fungal infections with radiological progression after receipt of amphotericin B or
             active triazole for greater than 1 month

          -  Patients with active bacterial or fungal infections unresponsive to medical therapy

          -  Patients with the following organ dysfunction symptomatic coronary artery disease or
             ejection fraction < 35% or other cardiac failure requiring therapy; ejection fraction
             is required if the patient is > 50 years of age, or history of cardiac disease or
             anthracycline exposure

               -  Diffusion capacity of carbon monoxide (DLCO) < 35%; total lung capacity (TLC) <
                  35%; or forced expiratory volume in one second (FEV1) < 35% and/or receiving
                  supplementary continuous oxygen

               -  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 >3 mg/dL; or symptomatic biliary disease

               -  Patients with poorly controlled hypertension on multiple antihypertensives

               -  Karnofsky score < 70 for adult patients

               -  Lansky-Play Performance Score < 50 for pediatric patients

          -  DONOR: Bone marrow (BM) donors

          -  DONOR: Donors who are HIV-positive and/or, medical conditions that would result in
             increased risk for granulocyte colony-stimulating factor (G-CSF) mobilization and
             harvest of peripheral blood stem cell (PBSC)

          -  DONOR: Donors < 12 years of age