Sirolimus, Tacrolimus, and Antithymocyte Globulin in Preventing Graft-Versus-Host Disease in Patients With Hematologic Cancer Who Are Undergoing Donor Stem Cell Transplant
Condition: Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; 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; Myelodysplastic-Myeloproliferative Diseases; Graft vs Host Disease; Syndrome
Intervention: rituximab; busulfan; carmustine; cyclophosphamide; cytarabine; etoposide; fludarabine phosphate; melphalan; total body irradiation (TBI); anti-thymocyte globulin IV
Intervention description: Given IV; Given IV; Given IV; Given IV; Given IV; Given IV; Given IV; Given IV; Given once or twice daily; Given IV
Intervention MeSH terms: Cytarabine; Cyclophosphamide; Melphalan; Busulfan; Carmustine; Rituximab; Fludarabine; Fludarabine phosphate; Etoposide; Thymoglobulin; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage III adult Burkitt lymphoma; stage III adult diffuse large cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage III adult diffuse small cleaved cell lymphoma; stage III adult Hodgkin lymphoma; stage III adult immunoblastic large cell lymphoma; stage III adult lymphoblastic lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage III mantle cell lymphoma; stage III marginal zone lymphoma; stage III small lymphocytic lymphoma; stage IV adult Burkitt lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult diffuse mixed cell lymphoma; stage IV adult diffuse small cleaved cell lymphoma; stage IV adult Hodgkin lymphoma; stage IV adult immunoblastic large cell lymphoma; stage IV adult lymphoblastic lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; stage IV mantle cell lymphoma; stage IV marginal zone lymphoma; stage IV small lymphocytic lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; noncontiguous stage II adult Burkitt lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse mixed cell lymphoma; noncontiguous stage II adult diffuse small cleaved cell lymphoma; noncontiguous stage II adult immunoblastic large cell lymphoma; noncontiguous stage II adult lymphoblastic lymphoma; noncontiguous stage II grade 1 follicular lymphoma; noncontiguous stage II grade 2 follicular lymphoma; noncontiguous stage II grade 3 follicular lymphoma; noncontiguous stage II mantle cell lymphoma; noncontiguous stage II marginal zone lymphoma; noncontiguous stage II small lymphocytic lymphoma; accelerated phase chronic myelogenous leukemia; adult acute lymphoblastic leukemia in remission; adult acute myeloid leukemia in remission; 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); chronic phase chronic myelogenous leukemia; recurrent adult acute lymphoblastic leukemia; recurrent adult acute myeloid leukemia; secondary acute myeloid leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; de novo myelodysplastic syndromes; myelodysplastic/myeloproliferative neoplasm, unclassifiable; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; primary myelofibrosis; atypical chronic myeloid leukemia, BCR-ABL negative; chronic eosinophilic leukemia; chronic myelomonocytic leukemia; chronic neutrophilic leukemia

Summary:

      RATIONALE: Giving low doses of chemotherapy, monoclonal antibodies, and radiation therapy
      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. 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 tacrolimus, sirolimus,
      and antithymocyte globulin before and after transplant may stop this from happening.

      PURPOSE: This phase II trial is studying the side effects of giving sirolimus together with
      tacrolimus and antithymocyte globulin and to see how well it works in preventing
      graft-versus-host disease in patients with hematologic cancer who are undergoing donor stem
      cell transplant.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of a hematological malignancy, including any of the following:

               -  Non-Hodgkin lymphoma in complete remission (CR) or partial remission (PR)

               -  Hodgkin lymphoma in CR or PR

               -  Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) meeting either
                  of the following criteria:

                    -  In CR

                    -  Not in CR and meets the following criteria:

                         -  Bone marrow blast < 20% within 4 weeks of transplantation

                         -  Peripheral blood absolute blast count < 500 per microliter on the day
                            of initiating conditioning therapy

               -  Myelodysplastic syndromes, treated or untreated

               -  Chronic myeloid leukemia in chronic phase or accelerated phase

               -  Multiple myeloma in CR or PR

               -  Chronic lymphocytic leukemia in second or greater CR or PR

               -  Myelofibrosis or other myeloproliferative disorders meeting the following
                  criteria:

                    -  Bone marrow blasts < 20% within 4 weeks of transplantation

                    -  Peripheral blood absolute blast count < 500 per microliter on the day of
                       initiating conditioning therapy

                    -  Patients with ascites not allowed

          -  No prior bone marrow or ex vivo engineered or processed graft (i.e., CD34+ enrichment,
             T-cell depletion, etc)

          -  Scheduled to undergo peripheral blood stem cell transplantation from a suitable
             HLA-matched or -mismatched unrelated donor, as determined by treating physician

               -  High resolution molecular HLA typing is required for HLA class I and II

               -  No more than one antigen or allele mismatch

          -  No documented uncontrolled CNS disease

        PATIENT CHARACTERISTICS:

          -  ECOG performance status (PS) 0-2

          -  Karnofsky PS 60-100%

          -  Creatinine clearance > 50 mL/min

          -  Bilirubin < 3 times upper limit of normal (ULN)

          -  ALT and AST < 3 times ULN

          -  LVEF > 50%

          -  FVC, FEV_1, or DLCO > 50% predicted

               -  Patients on home oxygen not allowed

          -  Able to cooperate with oral medication intake

          -  HIV negative

          -  No active hepatitis B or hepatitis C

          -  No known contraindication to sirolimus, tacrolimus, or anti-thymocyte globulin

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics