Clinical trial NCT00771875
Conditions: Graft Rejection
Sponsor: University of Cincinnati
Start date: 2008-09-01; Completion date: 2013-03-01
Enrollment: 30 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study is being conducted to determine how safe and effective using an immune cell (b cell) depleting therapy and/or Thymoglobulin is in patients with a kidney transplant who are experiencing certain types of rejection.

Detailed description:
The purpose of the study is to determine safety and efficacy of treatment if mixed (cellular and antibody) mediated acute rejection with addition of B-cell depleting therapy to Thymoglobulin in kidney and simultaneous kidney pancreas allograft recipients.

Arms: arm 1: Rabbit Antithymocyte Globulin (RATG) All patients will receive RATG (Thymoglobulin) dosed based on CD3 count. Patients will be redosed when the cluster of differentiation 3 (CD3) count is ≥ 25. Depending on rejection severity, Thymoglobulin will be given for a maximum of 7-14 days. CD3 levels will be monitored daily. 1.5mg/kg/day over 6 hrs with 1st dose (D1) and over 4 hours for each dose thereafter. (day 1 then when CD3 levels \> 25 cells/mm3); Patients will be premedicated with an antihistamine and acetaminophen prior to dosing per institution standard of care. Methylprednisolone 250 mg with 1st dose of Thymoglobulin. Methylprednisolone 125 mg on treatment day 2 subsequent corticosteroids per institution standard of care; following treatment, corticosteroid therapy will resume at the pre-rejection dose. arm 2: Rabbit Antithymocyte Globulin (RATG) + Rituximab Subjects will be given 1.5mg/kg/day of RATG over 6 hrs with 1st dose (D1) and over 4 hours for each dose thereafter. (day 1 then when CD3 levels \> 25 cells/mm3); Patients will be premedicated with an antihistamine and acetaminophen prior to dosing per institution standard of care. Rituximab dose of 375 mg/ m2 on day 2. Patients will be premedicated with an antihistamine and acetaminophen prior to dosing per institution standard of care. Methylprednisolone 250 mg with 1st dose of Thymoglobulin. Methylprednisolone 125 mg on treatment day 2 subsequent corticosteroids per institution standard of care; following treatment, corticosteroid therapy will resume at the pre-rejection dose. arm 3: Rabbit Antithymocyte Globulin (RATG) + Bortezomib -Subjects will be given 1.5mg/kg/day of RATG over 6 hrs with 1st dose (D1) and over 4 hours for each dose thereafter. (day 1 then when CD3 levels \> 25 cells/mm3). Patients will be premedicated with an antihistamine and acetaminophen prior to dosing per institution standard of care. Bortezomib will be given at a dose of 1.3 mg/m2 via IV push over 3-5 seconds on days 2, 5, 9, and 12. Methylprednisolone will be administered prior to each bortezomib dose. On days 2 and 5, administer methylprednisolone 100 mg intravenous push (IVP). On days 9 and 12, administer methylprednisolone 50 mg intravenous push (IVP). If thymoglobulin is administered the same day as bortezomib, the order of administration is- methylprednisolone, then bortezomib, then thymoglobulin.
Interventions: intervention 1: Rabbit Antithymocyte Globulin (RATG) intervention 2: Rituximab intervention 3: Bortezomib intervention 4: Acetaminophen intervention 5: Antihistamine intervention 6: Methylprednisolone
Intervention descriptions: intervention 1: All patients will receive Thymoglobulin dosed based on CD3 count. Patients will be redosed when the CD3 count is ≥ 25. Depending on rejection severity, Thymoglobulin will be given for a maximum of 7-14 days. CD3 levels will be monitored daily. intervention 2: Rituximab dose of 375 mg/ m2 on day 2. Patients will be premedicated with an antihistamine and acetaminophen prior to dosing per institution standard of care. intervention 3: Patient will receive 1.3 mg/m2 via IV push over 3-5 seconds on days 2, 5, 9, and 12. Consolidation course of bortezomib will be dosed at 1.3 mg/m2 IVP X 4 doses administered on days 1, 4, 7 and 10. intervention 4: Patients will be premedicated with acetaminophen prior to dosing per institution standard of care. intervention 5: Patients will be premedicated with an antihistamine prior to dosing per institution standard of care. intervention 6: Methylprednisolone 250 mg with 1st dose of Thymoglobulin. Methylprednisolone 125 mg on treatment day 2 subsequent corticosteroids per institution standard of care; following treatment, corticosteroid therapy will resume at the pre-rejection dose.

Protocol documents: