Sirolimus, Tacrolimus, and Antithymocyte Globulin in Preventing Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant For Hematological Cancer
Condition: Chronic Myeloproliferative Disorders; Graft Versus Host Disease; Infection; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Precancerous Condition; Secondary Myelofibrosis; Small Intestine Cancer
MeSH terms: Lymphoma; Leukemia; Neoplasms; Multiple Myeloma; Neoplasms, Plasma Cell; Preleukemia; Neoplasm Metastasis; Plasmacytoma; Precancerous Conditions; Intestinal Neoplasms; Myelodysplastic Syndromes; Primary Myelofibrosis; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Graft vs Host Disease; Syndrome
Intervention: anti-thymocyte globulin; cyclophosphamide; etoposide; fludarabine phosphate; melphalan; methotrexate; sirolimus; tacrolimus; allogeneic hematopoietic stem cell transplantation; hematopoietic stem cell transplantation; nonmyeloablative allogeneic hematopoietic stem cell transplantation; peripheral blood stem cell transplantation; total-body irradiation
Intervention description: 0.5 mg/kg on day -3, 1.5 mg/kg on day -2 and 2.5 mg/kg on day -1 or day 0 from stem cell transplant; 60mg/kg on days -5 and -4 from stem cell transplant; 60mg/kg on day -4 from stem cell transplant; Fludarabine 25 mg/m2/d from days -9 to -5 from stem cell transplant; Melphalan 140 mg/m2 on day -4 from stem cell transplant; For high risk HLA-mismatch transplant only: 5 mg/m2 on days +1, +3 and +6 from stem cell transplant; Adults: 12 mg loading dose on day -3 from stem cell transplant followed by 4 mg orally single morning daily dose.
Pediatric Patients <40kg: 3 mg/m2 orally on day -3 from stem cell transplant followed by 1 mg/m2 orally single morning daily dose; 0.02 mg/kd/d CIV beginning on day -3 from stem cell transplant; The target peripheral blood stem cell dose will be 5-10 x 106/kg actual body weight; The target peripheral blood stem cell dose will be 5-10 x 106/kg actual body weight; Fludarabine 25 mg/m2/d from days -9 to -5 from stem cell transplant, Melphalan 140 mg/m2 on day -4 from stem cell transplant; The target peripheral blood stem cell dose will be 5-10 x 106/kg actual body weight; 1320 cGy in 11 fractions from day -8 to day -5 or day -9 to day -6 prior to stem cell transplant
Intervention MeSH terms: Sirolimus; Cyclophosphamide; Melphalan; Methotrexate; Fludarabine; Fludarabine phosphate; Etoposide; Tacrolimus; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 2 Years
Healthy volunteers: No
Keywords: graft versus host disease; infection; adult favorable prognosis Hodgkin lymphoma; adult unfavorable prognosis Hodgkin lymphoma; childhood favorable prognosis Hodgkin lymphoma; childhood unfavorable prognosis Hodgkin lymphoma; cutaneous B-cell non-Hodgkin lymphoma; recurrent adult Hodgkin lymphoma; recurrent cutaneous T-cell non-Hodgkin lymphoma; recurrent/refractory childhood Hodgkin lymphoma; stage I adult Hodgkin lymphoma; stage I childhood Hodgkin lymphoma; stage I cutaneous T-cell non-Hodgkin lymphoma; stage II adult Hodgkin lymphoma; stage II childhood Hodgkin lymphoma; stage II cutaneous T-cell non-Hodgkin lymphoma; stage III adult Hodgkin lymphoma; stage III childhood Hodgkin lymphoma; stage III cutaneous T-cell non-Hodgkin lymphoma; stage IV adult Hodgkin lymphoma; stage IV childhood Hodgkin lymphoma; stage IV cutaneous T-cell non-Hodgkin lymphoma; anaplastic large cell lymphoma; angioimmunoblastic T-cell lymphoma; Burkitt lymphoma; contiguous stage II adult Burkitt lymphoma; contiguous stage II adult diffuse large cell lymphoma; contiguous stage II adult diffuse mixed cell lymphoma; contiguous stage II adult diffuse small cleaved cell lymphoma; contiguous stage II adult immunoblastic large cell lymphoma; contiguous stage II adult lymphoblastic lymphoma; contiguous stage II grade 1 follicular lymphoma; contiguous stage II grade 2 follicular lymphoma; contiguous stage II grade 3 follicular lymphoma; contiguous stage II mantle cell lymphoma; contiguous stage II marginal zone lymphoma; contiguous stage II small lymphocytic lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell 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; 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 adult T-cell leukemia/lymphoma; recurrent childhood anaplastic large cell lymphoma; recurrent childhood grade III lymphomatoid granulomatosis; recurrent childhood lymphoblastic lymphoma; recurrent childhood small noncleaved cell lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent grade I lymphomatoid granulomatosis; recurrent grade II lymphomatoid granulomatosis; recurrent mantle cell lymphoma; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; small intestine lymphoma; splenic marginal zone lymphoma; stage I adult Burkitt lymphoma; stage I adult diffuse large cell lymphoma; stage I adult diffuse mixed cell lymphoma; stage I adult diffuse small cleaved cell lymphoma; stage I adult immunoblastic large cell lymphoma; stage I adult lymphoblastic lymphoma; stage I adult T-cell leukemia/lymphoma; 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 immunoblastic large cell lymphoma; stage III adult lymphoblastic lymphoma; stage III adult T-cell leukemia/lymphoma; stage III childhood anaplastic large cell lymphoma; stage III childhood lymphoblastic lymphoma; stage III childhood small noncleaved cell 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 immunoblastic large cell lymphoma; stage IV adult lymphoblastic lymphoma; stage IV adult T-cell leukemia/lymphoma; stage IV childhood anaplastic large cell lymphoma; stage IV childhood lymphoblastic lymphoma; stage IV childhood small noncleaved cell 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; 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); childhood acute myeloid leukemia in remission; recurrent adult acute myeloid leukemia; recurrent childhood acute myeloid leukemia; secondary acute myeloid leukemia; adult acute lymphoblastic leukemia in remission; childhood acute lymphoblastic leukemia in remission; recurrent adult acute lymphoblastic leukemia; recurrent childhood acute lymphoblastic leukemia; accelerated phase chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; refractory chronic lymphocytic leukemia; relapsing chronic myelogenous leukemia; stage I chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; childhood myelodysplastic syndromes; de novo myelodysplastic syndromes; myelodysplastic/myeloproliferative neoplasm, unclassifiable; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; atypical chronic myeloid leukemia, BCR-ABL negative; chronic myelomonocytic leukemia; juvenile myelomonocytic leukemia; primary myelofibrosis; secondary myelofibrosis

Summary:

      RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood
      stem cell transplant helps stop the growth of cancer cells. It 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 tacrolimus, sirolimus, antithymocyte globulin, and
      methotrexate before and after transplant may stop this from happening.

      PURPOSE: This phase II trial is studying how well sirolimus, tacrolimus, and antithymocyte
      globulin work in preventing graft-versus-host disease in patients undergoing a donor stem
      cell transplant for hematological cancer .
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of hematological malignancy including any of the following:

               -  Non-Hodgkin lymphoma (NHL) in any complete remission (CR) or partial response
                  (PR)

               -  Hodgkin lymphoma in any CR or PR

               -  Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) in any CR

                    -  Bone marrow blasts < 20% within 4 weeks of transplant and peripheral blood
                       absolute blast count < 500/µL on the day of initiation of conditioning for
                       patients with non-CR AML or ALL

               -  Myelodysplastic syndromes (MDS) treated or untreated

               -  Chronic myelogenous leukemia (CML) in chronic or accelerated phase

               -  Multiple myeloma in any CR or PR

               -  Chronic lymphocytic leukemia in CR or PR 2 or greater

               -  Myelofibrosis and other myeloproliferative disorders

                    -  Bone marrow blasts < 20% within 4 weeks of transplant and peripheral blood
                       absolute blast count < 500/µL on the day of initiation

          -  High-risk disease defined as AML or ALL > CR1, accelerated phase CML, recurrent
             aggressive lymphoma, or active lymphoproliferative disease at transplant

          -  Low-risk disease defined as AML or ALL in CR1, chronic phase CML, or low-grade
             lymphoproliferative disorder with controlled disease at transplant

          -  Must be planning to receive 1 of the following conditioning regimens at City of Hope:

               -  Fludarabine phosphate and melphalan for patients with hematological malignancies
                  and contraindications for conventional myeloablative regimens due to age,
                  co-morbidity, or previous transplant

               -  Fractionated total-body irradiation (FTBI) and etoposide for patients with AML
                  and ALL or CML in accelerated phase

               -  FTBI and cyclophosphamide for patients with NHL, AML, CML, and MDS

          -  Suitable unrelated donor available

               -  HLA-matched or mismatched

               -  Peripheral blood stem cells available

               -  No bone marrow or ex vivo-engineered or processed graft (e.g., CD34-positive,
                  T-cell depletion)

          -  No uncontrolled CNS disease

        PATIENT CHARACTERISTICS:

          -  Karnofsky performance status (PS) 70-100% or ECOG PS 0-2

          -  Creatinine < 1.3 mg/dL or creatinine clearance ≥ 70 mL/min

          -  Ejection fraction > 45%

          -  Direct bilirubin < 3 times upper limit of normal (ULN)

          -  ALT and AST < 3 times ULN

          -  Forced vital capacity, FEV1, and DLCO > 45% of predicted

          -  Able to cooperate with oral medication intake

          -  No active donor or recipient serology positive for HIV

          -  No known contraindication to administration of sirolimus, tacrolimus, or
             anti-thymocyte globulin

          -  No active hepatitis B or C

          -  Negative pregnancy test

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  Concurrent participation in other clinical trials for prevention or treatment of
             viral, bacterial, or fungal disease allowed provided agents do not interact with
             agents used in the current study