Randomized Trial for Mixed Acute Rejection
Phase 2
Completed
- Conditions
- Graft Rejection
- Interventions
- Registration Number
- NCT00771875
- Lead Sponsor
- University of Cincinnati
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 30
Inclusion Criteria
Not provided
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description RATG/Bortezomib Antihistamine 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. Rabbit Antithymocyte Globulin (RATG) Antihistamine 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. RATG/Rituximab Antihistamine 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. Rabbit Antithymocyte Globulin (RATG) Rabbit Antithymocyte Globulin (RATG) 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. Rabbit Antithymocyte Globulin (RATG) Rituximab 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. Rabbit Antithymocyte Globulin (RATG) Bortezomib 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. Rabbit Antithymocyte Globulin (RATG) Acetaminophen 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. RATG/Rituximab Rituximab 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. RATG/Rituximab Acetaminophen 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. RATG/Bortezomib Bortezomib 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. RATG/Bortezomib Acetaminophen 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. Rabbit Antithymocyte Globulin (RATG) Methylprednisolone 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. RATG/Rituximab Methylprednisolone 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. RATG/Bortezomib Methylprednisolone 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.
- Primary Outcome Measures
Name Time Method Number of Patients in Each Group With Any of the Following: Rejection Reversal or Recurrent Rejection 1 year Rejection Reversal is a return of serum creatinine to within 115% of the baseline value, or histologic reversal occurring within 14 days of initiation of treatment.
Recurrent Rejection is histologic evidence of rejection noted on a biopsy specimen obtained up to 3 months after documented rejection reversal.
- Secondary Outcome Measures
Name Time Method Number of Patients With Allografts With C4d Focal Positive Pretreatment Biopsy Day 1 Renal Allograft Survival 1 year after rejection treatment Mean Serum Creatinine 7, 14, 28, 60, 90 days and 1 year post therapy initiation Renal allograft function as determined by change (∆) in Calculated creatinine clearance by Cockcroft-Gault at 7, 14, 28, 60, and 90 days and 1 year post therapy initiation
Incidence of Death 90 days Number of Patients With Allografts With C4d Diffuse Positive Pretreatment Biopsy 90 days Incidence of Post Transplant Lymphoproliferative Disorder (PTLD) 1 year
Trial Locations
- Locations (2)
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
The Christ Hospital
🇺🇸Cincinnati, Ohio, United States