Clinical trial NCT00617929
Conditions: Cancer
Keywords: chronic myelogenous leukemia acute lymphoblastic leukemia chronic myeloid leukemia lymphoblastic leukemia acute myeloid leukemia chronic eosinophilic leukemia primary myelofibrosis chronic myelomonocytic leukemia chronic neutrophilic leukemia de novo myelodysplastic syndromes disseminated neuroblastoma juvenile myelomonocytic leukemia Burkitt lymphoma rhabdomyosarcoma myelodysplastic syndromes Hodgkin lymphoma lymphoblastic lymphoma breast cancer follicular lymphoma mantle cell lymphoma marginal zone lymphoma recurrent neuroblastoma recurrent ovarian epithelial cancer recurrent ovarian germ cell tumor recurrent small lymphocytic lymphoma recurrent malignant testicular germ cell tumor recurrent Wilms tumor and other childhood kidney tumors recurrent/refractory childhood Hodgkin lymphoma refractory hairy cell leukemia refractory multiple myeloma relapsing chronic myelogenous leukemia secondary acute myeloid leukemia secondary myelodysplastic syndromes splenic marginal zone lymphoma stage I multiple myeloma stage II multiple myeloma stage III multiple myeloma stage II ovarian epithelial cancer 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 Hodgkin 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 ovarian epithelial cancer stage III small lymphocytic lymphoma stage III malignant testicular germ cell tumor stage IIIA breast cancer stage IIIB breast cancer stage IIIC breast cancer 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 Hodgkin lymphoma stage IV adult immunoblastic large cell lymphoma stage IV adult lymphoblastic lymphoma stage IV breast cancer 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 ovarian epithelial cancer stage IV small lymphocytic lymphoma refractory chronic lymphocytic leukemia
Sponsor: Masonic Cancer Center, University of Minnesota
Start date: 2008-01-01; Completion date: 2015-10-01
Enrollment: 12 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Antithymocyte globulin, clofarabine, and rituximab may stop the patient's immune system from rejecting the donor's stem cells when they do not exactly match the patient's blood. 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 antithymocyte globulin before transplant and cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving antithymocyte globulin together with clofarabine and rituximab works in treating patients after an unsuccessful stem cell transplant.

Detailed description:
OBJECTIVES:

Primary

* To determine the rate of sustained donor engraftment at 42 days and survival at 100 days post transplantation in patients treated with anti-thymocyte globulin, clofarabine, and rituximab.

Secondary

* To determine incidence of treatment-related mortality at day 100 post transplantation.
* To determine incidence of neutrophil recovery by day 42 post transplantation.
* To determine survival at day 100 and 1 year post transplantation.
* To determine the proportion of patients with chimerism at day 28 post transplantation.
* To determine incidence and severity of grades II-IV acute graft-vs-host disease by day 100 post transplantation.

OUTLINE:

* Conditioning regimen: Patients receive rituximab intravenously (IV) on day -7, anti-thymocyte globulin IV over 4-6 hours on days -6 to -4, and clofarabine IV over 1 hour on days -4 to -2.
* Hematopoietic stem cell transplantation (HSCT): Patients undergo HSCT on day 0. Patients may receive umbilical cord blood, peripheral blood stem cells, or bone marrow from unrelated or related donors.
* Graft-vs-host disease (GVHD) prophylaxis: Patients receive oral cyclosporine twice daily or cyclosporine IV every 8 hours beginning on day -3 and continuing for 100 or 180 days post transplantation followed by a taper; mycophenolate mofetil IV every 8 hours beginning on day -3 and continuing for 30 days (or 7 days after engraftment with no evidence of GVHD); and filgrastim (G-CSF) IV once daily beginning on day 1 and continuing until blood counts recover.

After completion of study therapy, patients are followed on days 100, 180, and 360.

Arms: arm 1: Primary or secondary graft failure after hematopoietic stem cell transplantation defined as a \> 50% loss of previously best donor chimerism or less than 25% donor chimerism beyond day +42 with pancytopenia and no evidence of relapse. Patients with any diagnosis, type of donor, hematopoietic cell graft or conditioning regimen should be considered for this study. Patients receive anti-thymocyte globulin, rituximab, and clofarabine.
Interventions: intervention 1: anti-thymocyte globulin intervention 2: rituximab intervention 3: clofarabine intervention 4: stem cell transplantation
Intervention descriptions: intervention 1: administer 3 mg/kg intravenously (IV) over 4 hours on days -6, -5 and -4. intervention 2: administered 375 mg/m\^2 intravenously (IV) in 1 mg/mL normal saline on day -7. intervention 3: administered 30 mg/m\^2 intravenously (IV) over 1 hour on Days -4, -3, and -2. intervention 4: administered on Day 0 per institutional guidelines.

Protocol documents: