Clinical trial NCT00611351
Conditions: Graft Versus Host Disease Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases Secondary Myelofibrosis
Keywords: graft versus host disease 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) recurrent adult acute myeloid leukemia untreated adult acute myeloid leukemia untreated adult acute lymphoblastic leukemia accelerated phase chronic myelogenous leukemia blastic phase chronic myelogenous leukemia chronic phase chronic myelogenous leukemia relapsing chronic myelogenous leukemia stage III multiple myeloma refractory multiple myeloma de novo myelodysplastic syndromes myelodysplastic/myeloproliferative disease, unclassifiable previously treated myelodysplastic syndromes secondary myelodysplastic syndromes secondary myelofibrosis secondary 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 Hodgkin lymphoma recurrent adult immunoblastic large cell lymphoma recurrent adult lymphoblastic lymphoma recurrent adult T-cell leukemia/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 small lymphocytic lymphoma recurrent adult acute lymphoblastic leukemia extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue nodal marginal zone B-cell lymphoma splenic marginal zone lymphoma adult nasal type extranodal NK/T-cell lymphoma stage III adult Hodgkin lymphoma stage IV adult Hodgkin lymphoma stage III adult T-cell leukemia/lymphoma stage IV adult T-cell leukemia/lymphoma stage III adult Burkitt lymphoma stage IV adult Burkitt lymphoma stage III adult diffuse large cell lymphoma stage IV adult diffuse large cell lymphoma stage III adult diffuse mixed cell lymphoma stage IV adult diffuse mixed cell lymphoma stage III adult immunoblastic large cell lymphoma stage IV adult immunoblastic large cell lymphoma stage III adult lymphoblastic lymphoma stage IV adult lymphoblastic lymphoma stage III grade 1 follicular lymphoma stage III grade 2 follicular lymphoma stage III grade 3 follicular lymphoma stage IV grade 1 follicular lymphoma stage IV grade 2 follicular lymphoma stage IV grade 3 follicular lymphoma stage III mantle cell lymphoma stage IV mantle cell lymphoma stage III marginal zone lymphoma stage IV marginal zone lymphoma stage III small lymphocytic lymphoma stage IV small lymphocytic lymphoma stage III adult diffuse small cleaved cell lymphoma stage IV adult diffuse small cleaved cell lymphoma adult acute lymphoblastic leukemia in remission adult acute myeloid leukemia in remission atypical chronic myeloid leukemia 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 refractory hairy cell leukemia stage I multiple myeloma stage II multiple myeloma
Sponsor: University of Nebraska
Start date: 2005-06-07; Completion date: 2008-09-17
Enrollment: 5 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Giving chemotherapy before a donor bone marrow transplant or peripheral stem cell transplant helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem cells. When certain 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 make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving busulfan together with cyclophosphamide and antithymocyte globulin followed by donor stem cell transplant works in treating patients with hematologic cancer.

Detailed description:
OBJECTIVES:

Primary

* To determine the incidence of grade II-IV acute graft-versus-host disease in patients with hematologic cancer or other diseases treated with a myeloablative conditioning regimen comprising targeted (steady-state concentration of 800-1,000 ng/mL) busulfan, cyclophosphamide, and anti-thymocyte globulin followed by matched unrelated donor allogeneic hematopoietic stem cell transplantation.
* To determine the day +100 transplantation-related mortality in these patients.

Secondary

* To determine the effect of cyclophosphamide pharmacokinetic parameters on day +100 transplantation-related mortality in these patients.
* To determine the ability of low-dose anti-thymocyte globulin administered on day +5 to induce activation-induced cell death of activated donor lymphocytes.
* To determine the incidence of chronic graft-versus-host disease in patients treated with this regimen.
* To determine event-free and overall survival of patients treated with this regimen.
* To evaluate pharmacogenomic associations between genetic polymorphisms in drug disposition enzymes with the pharmacokinetics of busulfan and cyclophosphamide.

OUTLINE:

* Myeloablative conditioning regimen: Patients receive busulfan IV over 2 hours on days -8 to -5; cyclophosphamide IV over 4 hours on days -3 to -2; and anti-thymocyte globulin IV over 6 hours on day -3 and then over 4 hours on days -2, -1, and 5.
* Allogeneic hematopoietic stem cell transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell infusion on day 0.
* Graft-versus-host-disease prophylaxis: Patients receive tacrolimus IV continuously or orally on days 6 to150, followed by an even taper to day 180 in the absence of graft-versus-host-disease. Patients also receive mycophenolate mofetil IV or orally beginning on day 6 and continuing to day 28.

Patients undergo blood collection periodically during study for pharmacokinetic, pharmacogenomic, and other translational studies. Genomic DNA extracted from blood samples is analyzed by polymerase chain reaction for genetic polymorphisms in cyclophosphamide/busulfan disposition enzymes. Activated donor lymphocytes are assessed using flow cytometry to measure activation-induced cell death, as reflected by apoptosis in activated T cells. Chimerism on or around day 100 is also assessed using fluorescence in situ hybridization analysis and DNA fingerprinting.

After completion of study treatment, patients are followed periodically.

Arms: arm 1: Matched unrelated donor allogeneic stem cell transplantation with a conditioning regimen of targeted busulfan, cyclophosphamide and thymoglobulin.
Interventions: intervention 1: anti-thymocyte globulin intervention 2: busulfan intervention 3: cyclophosphamide intervention 4: mycophenolate mofetil intervention 5: tacrolimus intervention 6: polymerase chain reaction intervention 7: polymorphism analysis intervention 8: flow cytometry intervention 9: laboratory biomarker analysis intervention 10: pharmacogenomic studies intervention 11: pharmacological study intervention 12: allogeneic bone marrow transplantation intervention 13: allogeneic hematopoietic stem cell transplantation intervention 14: peripheral blood stem cell transplantation
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: None intervention 6: None intervention 7: None intervention 8: None intervention 9: None intervention 10: None intervention 11: None intervention 12: None intervention 13: None intervention 14: None

Protocol documents: