Antithymocyte Globulin, Clofarabine, and Rituximab in Treating Patients After an Unsuccessful Stem Cell Transplant
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.
Biological: anti-thymocyte globulin
Procedure: stem cell transplantation
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Conditioning for Graft Failure After Hematopoietic Stem Cell Transplantation|
- Donor engraftment [ Time Frame: at 42 days post transplantation ] [ Designated as safety issue: No ]The process of transplanted stem cells reproducing new cells.
- Treatment-related Death [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]Number of patients who died related to the treatment in this study.
- Time to primary neutrophil engraftment [ Time Frame: at day 42 post transplantation ] [ Designated as safety issue: No ]blood test shows 500 or more neutrophils in a cubic millimeter of blood
- Overall Survival [ Time Frame: at day 100 and 1 year ] [ Designated as safety issue: No ]Number of patients alive from beginning of study to Day 100 and 1 year.
- Chimerism [ Time Frame: Day 28 ] [ Designated as safety issue: No ]the occurrence of genetically distinct cell types in a single organism
- Acute graft-vs-host disease [ Time Frame: Day 30-100 ] [ Designated as safety issue: No ]T-cells present in the donor's bone marrow at the time of transplant identify the BMT patient as "non-self' and attack the patient's skin, liver, stomach, and/or intestines.
|Study Start Date:||January 2008|
|Estimated Study Completion Date:||January 2016|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Conditioning for Graft Failure
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.
Biological: anti-thymocyte globulin
administer 3 mg/kg intravenously (IV) over 4 hours on days -6, -5 and -4.
Other Name: Thymoglobulin®Biological: rituximab
administered 375 mg/m^2 intravenously (IV) in 1 mg/mL normal saline on day -7.
Other Name: Rituxan(R)Drug: clofarabine
administered 30 mg/m^2 intravenously (IV) over 1 hour on Days -4, -3, and -2.
Other Name: CLOLAR™Procedure: stem cell transplantation
administered on Day 0 per institutional guidelines.
- 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.
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00617929
|Contact: Jakub Tolar, M.D.||firstname.lastname@example.org|
|United States, Minnesota|
|Masonic Cancer Center at University of Minnesota||Recruiting|
|Minneapolis, Minnesota, United States, 55455|
|Contact: Clinical Trials Office - Masonic Cancer Center at University o 612-624-2620|
|Principal Investigator:||Jakub Tolar, MD||Masonic Cancer Center, University of Minnesota|