Clinical trial NCT00719849
Conditions: Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases
Keywords: chronic myelogenous leukemia acute lymphoblastic leukemia acute myeloid leukemia atypical chronic myeloid leukemia chronic myelomonocytic leukemia anaplastic large cell lymphoma splenic marginal zone lymphoma nodal marginal zone B-cell lymphoma recurrent adult Hodgkin lymphoma recurrent adult diffuse large cell lymphoma recurrent adult immunoblastic large cell lymphoma recurrent childhood large cell lymphoma recurrent mycosis fungoides/Sezary syndrome 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/refractory childhood Hodgkin lymphoma childhood diffuse large cell lymphoma childhood immunoblastic large cell lymphoma refractory multiple myeloma de novo myelodysplastic syndromes previously treated myelodysplastic syndromes secondary myelodysplastic syndromes myelodysplastic/myeloproliferative disease childhood myelodysplastic syndromes recurrent childhood anaplastic large cell lymphoma refractory anemia refractory anemia with excess blasts refractory anemia with ringed sideroblasts refractory cytopenia with multilineage dysplasia stage III adult diffuse large cell lymphoma stage IV adult diffuse large cell lymphoma stage III adult immunoblastic large cell lymphoma stage IV adult immunoblastic large cell lymphoma stage III childhood anaplastic large cell lymphoma stage III childhood large cell lymphoma stage IV childhood anaplastic large cell lymphoma stage IV childhood large cell lymphoma stage III adult Hodgkin lymphoma stage III childhood Hodgkin lymphoma stage IV adult Hodgkin lymphoma stage IV childhood Hodgkin lymphoma stage II multiple myeloma stage III multiple myeloma stage III chronic lymphocytic leukemia stage IV chronic lymphocytic leukemia stage III small lymphocytic lymphoma stage IV small lymphocytic lymphoma stage III marginal zone lymphoma stage IV marginal zone 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 Waldenstrom macroglobulinemia stage III mantle cell lymphoma stage IV mantle cell lymphoma stage III mycosis fungoides/Sezary syndrome stage IV mycosis fungoides/Sezary syndrome juvenile myelomonocytic leukemia chronic eosinophilic leukemia chronic idiopathic myelofibrosis chronic neutrophilic leukemia essential thrombocythemia polycythemia vera
Sponsor: Fred Hutchinson Cancer Center
Start date: 2005-11-01; Completion date: 2009-12-01
Enrollment: 13 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
RATIONALE: Giving low doses of chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer or abnormal 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 cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well donor umbilical cord blood transplant with reduced intensity conditioning works in treating patients with advanced hematological cancer or other disease.

Detailed description:
OBJECTIVES:

Primary

* To estimate the probability of survival at 1 year in patients with advanced hematological malignancies or other diseases treated with non-myeloablative unrelated donor umbilical cord blood transplantation.

Secondary

* Six month non-relapse mortality.
* Chimerism at days 7, 14, 21, 28, 56, and 80, at 6 months, and at 1 and 2 years.
* To determine the incidence of neutrophil engraftment at day 42.
* To determine the incidence of platelet engraftment at 6 months.
* To determine the incidence of grade II-IV and III-IV acute graft-versus-host-disease (GVHD) at day 100.
* To determine the incidence of chronic GVHD at 1 year.
* To determine the incidence of clinically significant infections at 6 months and at 1 and 2 years.
* To determine the probability of progression-free survival at 1 and 2 years.
* To determine the probability of survival at 2 years.
* To determine the incidence of relapse or disease progression at 1 and 2 years.

OUTLINE: Patients are stratified according to disease status and prior therapy (hematologic malignancy or other disease that was treated with an autologous stem cell transplant or ≥ 2 courses of multiagent chemotherapy within the past 3 months vs hematologic malignancy or other disease that was treated with an autologous stem cell transplant \> 12 months ago or with ≤ 1 course of multiagent chemotherapy or immunosuppressive chemotherapy within the past 3 months vs refractory leukemia or lymphoma for which patient was rendered aplastic either by induction chemotherapy or radioimmunoconjugated monoclonal antibody therapy).

* Conditioning regimen: Patients receive fludarabine phosphate IV over 1 hour on days -6 to -2 and cyclophosphamide IV on day -6. Patients also undergo total body irradiation on day -1. Some patients also receive anti-thymocyte globulin IV on days -6 to -4.
* Umbilical cord blood transplantation (UCBT): Patients undergo UCBT on day 0.
* Immunosuppressive therapy (graft-versus-host disease prophylaxis): Patients receive cyclosporine IV over 1 hour or orally (as tolerated) every 8 or 12 hours beginning on day -3 and continuing for approximately 6 months. Patients also receive mycophenolate mofetil IV every 8 hours on days -3 to 5 and then orally on days 6-30.

After completion of study treatment, patients are followed at 6 months and then annually thereafter.

Arms: arm 1: Subjects with hematological malignancies with prior autologous transplant, \>2 cycles of multiagent chemotherapy, or severely immune suppressive therapy in last 3 months.

Refractory leukemia and lymphoma in aplasia after induction chemotherapy or radioimmunoconjugated monoclonal antibody therapy. arm 2: Subjects with hematological malignancies with prior autologous transplant \>12 mos or \<1 cycle of multiagent chemotherapy or NO immune suppressive chemotherapy in last 3 months
Interventions: intervention 1: anti-thymocyte globulin intervention 2: cyclophosphamide intervention 3: cyclosporine intervention 4: fludarabine phosphate intervention 5: mycophenolate mofetil intervention 6: umbilical cord blood transplantation intervention 7: total body irradiation
Intervention descriptions: intervention 1: 30mg/Kg Days -6 to -4 intervention 2: 50 mg/Kg Day -6 intervention 3: Patients will receive cyclosporine A (CSA) therapy beginning on Day -3 maintaining a trough level between 250 and 500 ng/mL. For adults the initial dose will be 2.5 mg/kg IV over 1 hour every 12 hours. For children \< 40 kg the initial dose will be 2.5 mg/kg IV over 1 hour every 8 hours. intervention 4: 40mg/m2 Days -6 to -2 intervention 5: 1 gram every 8 hours for patients who are ≥ 40 kg. Pediatric patients (\<40 kilograms) will receive MMF at the dose of 15 mg/kg/dose every 8 hours. Stop MMF at Day +30 or 7 days after engraftment, whichever day is later, if no acute GVHD. intervention 6: Single or double unit umbilical cord blood transplant intervention 7: 200 cGy Day -1

Protocol documents: