Donor Stem Cell Transplant in Treating Patients With Relapsed Hematologic Malignancies or Secondary Myelodysplasia Previously Treated With High-Dose Chemotherapy and Autologous Stem Cell Transplant
Condition: Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms
MeSH terms: Lymphoma; Leukemia; Neoplasms; Multiple Myeloma; Neoplasms, Plasma Cell; Preleukemia; Plasmacytoma; Myelodysplastic Syndromes; Myeloproliferative Disorders; Lymphoproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome
Intervention: anti-thymocyte globulin; donor lymphocytes; filgrastim; therapeutic allogeneic lymphocytes; busulfan; fludarabine phosphate; methotrexate; mycophenolate mofetil; tacrolimus; reduced-intensity transplant conditioning procedure; allogeneic hematopoietic stem cell transplantation; peripheral blood stem cell transplantation
Intervention MeSH terms: Mycophenolic Acid; Methotrexate; Fludarabine phosphate; Fludarabine; Busulfan; Tacrolimus; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Maximum age: 69 Years
Healthy volunteers: No
Keywords: adult acute myeloid leukemia with 11q23 (MLL) abnormalities; 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); juvenile myelomonocytic leukemia; prolymphocytic leukemia; recurrent adult acute myeloid leukemia; recurrent adult T-cell leukemia/lymphoma; recurrent childhood acute myeloid leukemia; refractory chronic lymphocytic leukemia; recurrent adult Hodgkin lymphoma; 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 immunoblastic large cell lymphoma; recurrent adult lymphoblastic 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 mycosis fungoides/Sezary syndrome; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent mantle cell lymphoma; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; recurrent/refractory childhood Hodgkin lymphoma; childhood diffuse large cell lymphoma; childhood grade III lymphomatoid granulomatosis; childhood immunoblastic large cell lymphoma; childhood nasal type extranodal NK/T-cell lymphoma; post-transplant lymphoproliferative disorder; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; refractory multiple myeloma; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; childhood myelodysplastic syndromes; recurrent childhood anaplastic large cell lymphoma; adult acute myelomonocytic leukemia (M4); childhood acute myelomonocytic leukemia (M4); adult acute minimally differentiated myeloid leukemia (M0); childhood acute minimally differentiated myeloid leukemia (M0); adult acute myeloblastic leukemia without maturation (M1); childhood acute myeloblastic leukemia without maturation (M1); adult acute myeloblastic leukemia with maturation (M2); childhood acute myeloblastic leukemia with maturation (M2); adult acute promyelocytic leukemia (M3); childhood acute promyelocytic leukemia (M3); adult acute monoblastic leukemia (M5a); adult acute monocytic leukemia (M5b); childhood acute monoblastic leukemia (M5a); childhood acute monocytic leukemia (M5b); adult erythroleukemia (M6a); adult pure erythroid leukemia (M6b); childhood acute erythroleukemia (M6); adult acute megakaryoblastic leukemia (M7); childhood acute megakaryocytic leukemia (M7); childhood Burkitt lymphoma; atypical chronic myeloid leukemia, BCR-ABL1 negative; chronic myelomonocytic leukemia; cutaneous B-cell non-Hodgkin lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; myelodysplastic/myeloproliferative neoplasm, unclassifiable

Summary:

      RATIONALE: Giving chemotherapy, such as busulfan and fludarabine phosphate, before a
      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. Sometimes the transplanted
      cells from a donor can make an immune response against the body's normal cells. Giving
      methotrexate, tacrolimus, and antithymocyte globulin before and after the transplant may stop
      this from happening. Once the donated stem cells begin working, the patient's immune system
      may see the remaining cancer cells as not belonging in the patient's body and destroy them
      (called graft-versus-tumor effect). Giving an infusion of the donor's white blood cells
      (donor lymphocyte infusion) may boost this effect.

      PURPOSE: This phase II trial is studying how well donor stem cell transplant works in
      treating patients with relapsed hematologic malignancies or secondary myelodysplasia
      previously treated with high-dose chemotherapy and autologous stem cell transplant .
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed hematologic malignancies:

               -  Chronic lymphocytic leukemia (CLL) or prolymphocytic leukemia (PLL)

                    -  Absolute lymphocytosis of > 5,000/μL

                    -  Lymphocytes must appear morphologically mature with < 55% prolymphocytes
                       (CLL)

                         -  Patients with > 55% prolymphocytes are considered as having PLL

                    -  Lymphocyte phenotype with expression of CD20, CD19, and CD5 (CLL)

               -  Non-Hodgkin lymphoma

                    -  Any WHO classification of histologic subtype

                    -  Core biopsies acceptable for primary diagnosis and immunophenotyping

                    -  Bone marrow biopsies as sole means of diagnosis not allowed for follicular
                       lymphoma

               -  Hodgkin lymphoma

                    -  Any WHO classification of histologic subtype

                    -  Core biopsies acceptable for primary diagnosis and immunophenotyping

                    -  Bone marrow biopsy is required

               -  Multiple myeloma

                    -  Patients must have active disease requiring treatment (Durie-Salmon stage
                       I-III)

               -  Acute myeloid leukemia

                    -  Must have < 10% bone marrow blasts and no circulating blasts

               -  Myelodysplastic syndrome (MDS)

                    -  MDS as define by WHO criteria

                    -  Must have < 10% marrow blasts

          -  Relapsed or progressive disease or myelodysplasia ≥ 6 months after prior high-dose
             chemotherapy with autologous hematopoietic cell support

               -  Prior syngeneic transplantation allowed

          -  Healthy donor meeting one of the following criteria:

               -  HLA-identical sibling (6/6)

                    -  Serologic typing for class I (A, B) and molecular typing for class II (DRB1)
                       required

               -  8/8 matched-unrelated donor

                    -  Molecular identity at HLA A, B, C, and DRB1 by high-resolution typing
                       required

               -  No syngeneic donors

        PATIENT CHARACTERISTICS:

          -  Creatinine clearance ≥ 40 mL/min

          -  Total bilirubin ≤ 2 mg/dL

          -  AST ≤ 3 times upper limit of normal

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  DLCO ≥ 40% with no symptomatic pulmonary disease

          -  LVEF ≥ 30% by MUGA or ECHO

          -  No uncontrolled diabetes mellitus or active serious infection

          -  No known hypersensitivity to E.coli-derived products

          -  No HIV infection

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  At least 4 weeks should elapse between prior standard cytotoxic chemotherapy,
             radiation therapy, or surgery and the planned start of the preparative regimen on day
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