Clinical trial NCT00589563
Conditions: 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
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
Sponsor: City of Hope Medical Center
Start date: 2007-05-01; Completion date: 2012-02-01
Enrollment: 32 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief 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 .

Detailed description:
OBJECTIVES:

Primary

* To determine the incidence and severity of acute- and chronic-graft-versus-host disease (GVHD) after HLA-matched or -mismatched unrelated donor hematopoietic peripheral blood transplantation in patients with hematologic malignancies scheduled to receive immunosuppressive combination of sirolimus, tacrolimus, and anti-thymocyte globulin as GVHD prophylaxis.
* To determine the safety of this combination in the first six months post-transplant.

Secondary

* To determine the time-to-engraftment, non-relapse mortality rate, overall and disease-free survival, incidence of disease relapse, and incidence of opportunistic infections with this GVHD prophylaxis.

OUTLINE: Patients are stratified according to conditioning regimen (fludarabine phosphate and melphalan vs fractionated total-body irradiation \[FTBI\] and etoposide vs FTBI and cyclophosphamide) and degree of donor/recipient HLA mismatch (high-risk vs low-risk).

* Conditioning regimen: Patients receive 1 of 3 standard conditioning regimens beginning on day -9 or -8 and continuing to day -1 or 0.
* Peripheral blood stem cell transplantation: Patients receive HLA-matched or mismatched unrelated donor peripheral blood stem cells on day 0.
* Graft-versus-host disease prophylaxis: Patients receive tacrolimus IV continuously beginning on day -3 and then orally when tolerated, oral sirolimus on days -3 and -2, anti-thymocyte globulin IV over 4-8 hours on days -3 to 0, and methotrexate\* IV on days 1, 3, and 6. Tacrolimus and sirolimus continue for 3-6 months (with taper).

NOTE: \*Only patients with high-risk HLA mismatch receive treatment with methotrexate.

After completion of study therapy, patients are followed periodically for up to 2 years.

Arms: arm 1: Fludarabine/Melphalan Conditioning with

Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis arm 2: FTBI/Cytoxan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis arm 3: FTBI/Etoposide Conditioning with

Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis
Interventions: intervention 1: anti-thymocyte globulin intervention 2: cyclophosphamide intervention 3: etoposide intervention 4: fludarabine phosphate intervention 5: melphalan intervention 6: methotrexate intervention 7: sirolimus intervention 8: tacrolimus intervention 9: allogeneic hematopoietic stem cell transplantation intervention 10: hematopoietic stem cell transplantation intervention 11: nonmyeloablative allogeneic hematopoietic stem cell transplantation intervention 12: peripheral blood stem cell transplantation intervention 13: total-body irradiation
Intervention descriptions: intervention 1: 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 intervention 2: 60mg/kg on days -5 and -4 from stem cell transplant intervention 3: 60mg/kg on day -4 from stem cell transplant intervention 4: Fludarabine 25 mg/m2/d from days -9 to -5 from stem cell transplant intervention 5: Melphalan 140 mg/m2 on day -4 from stem cell transplant intervention 6: For high risk HLA-mismatch transplant only: 5 mg/m2 on days +1, +3 and +6 from stem cell transplant intervention 7: 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 intervention 8: 0.02 mg/kd/d CIV beginning on day -3 from stem cell transplant intervention 9: The target peripheral blood stem cell dose will be 5-10 x 106/kg actual body weight intervention 10: The target peripheral blood stem cell dose will be 5-10 x 106/kg actual body weight intervention 11: 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 intervention 12: The target peripheral blood stem cell dose will be 5-10 x 106/kg actual body weight intervention 13: 1320 cGy in 11 fractions from day -8 to day -5 or day -9 to day -6 prior to stem cell transplant

Protocol documents: