Clinical trial NCT00608517
Conditions: Graft Versus Host Disease Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes
Keywords: graft versus host disease 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) blastic phase chronic myelogenous leukemia childhood acute lymphoblastic leukemia in remission childhood acute myeloid leukemia in remission childhood chronic myelogenous leukemia chronic phase chronic myelogenous leukemia de novo myelodysplastic syndromes extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue myelodysplastic/myeloproliferative disease, unclassifiable 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 adult non-Hodgkin 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 previously treated myelodysplastic syndromes secondary acute myeloid leukemia secondary myelodysplastic syndromes splenic marginal zone lymphoma stage I multiple myeloma stage II multiple myeloma refractory multiple myeloma stage III adult Burkitt lymphoma stage III adult Hodgkin 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 chronic lymphocytic leukemia 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 multiple myeloma stage III small lymphocytic lymphoma stage IV adult Burkitt lymphoma stage IV adult Hodgkin 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 chronic lymphocytic leukemia 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 Philadelphia chromosome positive adult precursor acute lymphoblastic leukemia Philadelphia chromosome positive childhood precursor acute lymphoblastic leukemia refractory chronic lymphocytic leukemia childhood myelodysplastic syndromes stage III adult T-cell leukemia/lymphoma stage IV adult T-cell leukemia/lymphoma adult nasal type extranodal NK/T-cell lymphoma childhood nasal type extranodal NK/T-cell lymphoma stage III cutaneous T-cell non-Hodgkin lymphoma stage IV cutaneous T-cell non-Hodgkin lymphoma recurrent cutaneous T-cell non-Hodgkin lymphoma recurrent adult T-cell leukemia/lymphoma
Sponsor: Vanderbilt-Ingram Cancer Center
Start date: 2005-09-01; Completion date: 2011-05-01
Enrollment: 6 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
RATIONALE: Giving chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy 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 before and after transplant may stop this from happening.

PURPOSE: To look at the ability of umbilical cord blood cells from one or two unrelated donors to serve as a source of stem cells for people needing a bone marrow transplant.

Detailed description:
OBJECTIVES:

Primary

* To determine the safety (as assessed by the day 100 non-relapse mortality) and feasibility of single or double umbilical cord stem cell transplantation in patients with hematological malignancies receiving graft-versus-host disease (GVHD) prophylaxis comprising tacrolimus and mycophenolate mofetil (MMF).

Secondary

* To assess sustained donor engraftment, neutrophil recovery, platelet recovery, incidence and severity of acute graft-versus-host disease (GVHD) and chronic GVHD, relapse rate, 100-day all-cause mortality, overall survival, and immune reconstitution after single or double umbilical cord stem cell transplantation in patients with hematologic malignancies receiving graft-versus-host disease(GVHD) prophylaxis comprising tacrolimus and mycophenolate mofetil (MMF).

OUTLINE:

* Conditioning: Patients receive myeloablative or reduced-intensity conditioning regimen according to age and prior treatment.

  * Myeloablative conditioning (pediatric patients): Patients undergo total-body irradiation on days -7 to -4, and receive cyclophosphamide IV over 1 hour on days -3 and -2, methylprednisolone IV twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4 hours on days -3 to -1.
  * Myeloablative conditioning (adult patients 18-40 years old): Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -4, cyclophosphamide IV over 1 hour on days -5 and -4, and undergo total-body irradiation on days -3 to -1.
  * Reduced-intensity conditioning (patients over 40 and no more than 50 years old OR deemed ineligible for above myeloablative conditioning regimen due to previous treatment): Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on day -6 and undergo total-body irradiation on day -1.
* Umbilical cord blood transplantation (UCBT): All patients undergo single- or double-unit umbilical cord blood transplantation (UCBT)on day 0.
* Graft-versus-host disease prophylaxis: Patients receive tacrolimus IV continuously or orally twice daily on days -2 to 180 followed by a tapering and mycophenolate mofetil IV or orally twice daily on days 0-100 followed by a tapering over the next 3 months. Patients also receive filgrastim (G-CSF) IV or subcutaneously beginning on day 0\* and continuing until blood counts recover.

NOTE: \*In adult patients receiving a reduced intensity transplant, G-CSF will be started when the total white cell count falls below 2.5 x 109/L.

After completion of study treatment, patients are followed monthly for 1 year and then every 2-4 months thereafter.

Arms: arm 1: Patients undergo total-body irradiation on days -7 to -4, and receive cyclophosphamide IV over 1 hour on days -3 and -2, methylprednisolone IV twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4 hours on days -3 to -1. arm 2: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -4, cyclophosphamide IV over 1 hour on days -5 and -4, and undergo total-body irradiation on days -3 to -1. arm 3: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on day -6 and undergo total-body irradiation on day -1.
Interventions: intervention 1: anti-thymocyte globulin intervention 2: cyclophosphamide intervention 3: fludarabine phosphate intervention 4: methylprednisolone intervention 5: total-body irradiation
Intervention descriptions: intervention 1: Given IV intervention 2: Given IV intervention 3: Given IV intervention 4: Given IV intervention 5: Given daily for 1-4 days

Protocol documents: