Trial Outcomes & Findings for Randomized Trial of Induction Therapies in High Immunological Risk Kidney Transplant Recipients (NCT NCT00782821)
NCT ID: NCT00782821
Last Updated: 2016-01-20
Results Overview
Antibody mediated rejection demonstrated to be due to, atleast in part, to anti-donor antibody at 6 months by Banff 97' criteria. Acute rejection IA - cases with significant interstitial infiltration (\>25% of parenchyma affected) and foci of moderate tubulitis (\>4 mononuclear cells/tubular cross section or group of 10 tubular cells). IB - cases with significant interstitial infiltration (\>25% of parenchyma affected) and foci of severe tubulitis (\>10 mononuclear cells/tubular cross section or group of 10 tubular cells) IIA - cases with mild to moderate intimal arteritis (v1) IIB - cases with server intimal arteritis comprising \>25% of the luminal area (v2) III - case with transmural arteritis and/or arterial fibrinoid change and necrosis of medical smooth muscle cells (v3 with accompanying lymphoctic inflammation)
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
40 participants
Primary outcome timeframe
6 months
Results posted on
2016-01-20
Participant Flow
Participant milestones
| Measure |
RATG/Velcade
Thymoglobulin x 5 doses (1.5mg/kg IV) + Velcade (1.3 mg/m2 IVP)
Thymoglobulin is to be given on post operative days (POD) 0, 2, 4, 6 in all patients. Patients who receive a 5th dose will be administered a dose of Thymoglobulin on POD 8 and those who receive a 6th dose will be administered Thymoglobulin on POD 10. All groups will receive maintenance immunosuppression consisting of tacrolimus, mycophenolate mofetil, and corticosteroids (7 day corticosteroid taper to prednisone 5 mg daily). Patients randomized to Arm C or D will receive 1.3 mg/m2 via IVP over 3-5 minutes on POD 0, 3, 7 and 10. The dose administered on POD 0 will be administered before pre-operatively before the pre-operative dose of methylprednisolone.
|
RATG/Rituxan/Velcade
Thymoglobulin x 4 doses (1.5mg/kg IV). + Rituximab 200mg/m2 IV + Bortezomib 1.3 mg/m2 IVP Thymoglobulin is to be given on post operative days (POD) 0, 2, 4, 6 in all patients. Patients who receive a 5th dose will be administered a dose of Thymoglobulin on POD 8 and those who receive a 6th dose will be administered Thymoglobulin on POD 10. All groups will receive maintenance immunosuppression consisting of tacrolimus, mycophenolate mofetil, and corticosteroids (7 day corticosteroid taper to prednisone 5 mg daily). Patients randomized to Arm C or D will receive 1.3 mg/m2 via IVP over 3-5 minutes on POD 0, 3, 7 and 10. The dose administered on POD 0 will be administered before pre-operatively before the pre-operative dose of methylprednisolone.
|
Rabbit Antithymocyte Globulin (rATG)
Thymoglobulin x 6 doses (1.5mg/kg IV).
Thymoglobulin is to be given on post operative days (POD) 0, 2, 4, 6 in all patients. Patients who receive a 5th dose will be administered a dose of Thymoglobulin on POD 8 and those who receive a 6th dose will be administered Thymoglobulin on POD 10. All groups will receive maintenance immunosuppression consisting of tacrolimus, mycophenolate mofetil, and corticosteroids (7 day corticosteroid taper to prednisone 5 mg daily).
|
RATG/Rituxan
Thymoglobulin x 5 doses (1.5mg/kg IV) + Rituximab 375mg/m2 IV
Thymoglobulin is to be given on post operative days (POD) 0, 2, 4, 6 in all patients. Patients who receive a 5th dose will be administered a dose of Thymoglobulin on POD 8 and those who receive a 6th dose will be administered Thymoglobulin on POD 10. All groups will receive maintenance immunosuppression consisting of tacrolimus, mycophenolate mofetil, and corticosteroids (7 day corticosteroid taper to prednisone 5 mg daily).
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
10
|
10
|
10
|
10
|
|
Overall Study
COMPLETED
|
9
|
8
|
10
|
10
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Randomized Trial of Induction Therapies in High Immunological Risk Kidney Transplant Recipients
Baseline characteristics by cohort
| Measure |
Rabbit Antithymocyte Globulin (RATG)
n=10 Participants
Thymoglobulin (RATG) x 6 doses (1.5mg/kg IV) Thymoglobulin is to be given on post operative days (POD) 0, 2, 4, 6 in all patients. Patients who receive a 5th dose will be administered a dose of Thymoglobulin on POD 8 and those who receive a 6th dose will be administered Thymoglobulin on POD 10. All groups will receive maintenance immunosuppression consisting of tacrolimus, mycophenolate mofetil, and corticosteroids (7 day corticosteroid taper to prednisone 5 mg daily).
|
RATG/Rituxan
n=10 Participants
Thymoglobulin (RATG) x 5 doses (1.5mg/kg IV)+ Rituximab 375mg/m2 IV
Thymoglobulin is to be given on post operative days (POD) 0, 2, 4, 6 in all patients. Patients who receive a 5th dose will be administered a dose of Thymoglobulin on POD 8 and those who receive a 6th dose will be administered Thymoglobulin on POD 10. All groups will receive maintenance immunosuppression consisting of tacrolimus, mycophenolate mofetil, and corticosteroids (7 day corticosteroid taper to prednisone 5 mg daily).
|
RATG/Velcade
n=10 Participants
Thymoglobulin (RATG) x 5 doses (1.5mg/kg IV) + Velcade (1.3 mg/m2 IVP)
Thymoglobulin is to be given on post operative days (POD) 0, 2, 4, 6 in all patients. Patients who receive a 5th dose will be administered a dose of Thymoglobulin on POD 8 and those who receive a 6th dose will be administered Thymoglobulin on POD 10. All groups will receive maintenance immunosuppression consisting of tacrolimus, mycophenolate mofetil, and corticosteroids (7 day corticosteroid taper to prednisone 5 mg daily).
|
RATG/Rituxan/Velcade
n=10 Participants
Thymoglobulin x 4 doses (1.5mg/kg IV)+ Rituximab 200mg/m2 IV + Velcade (1.3 mg/m2 IVP)
Thymoglobulin is to be given on post operative days (POD) 0, 2, 4, 6 in all patients. Patients who receive a 5th dose will be administered a dose of Thymoglobulin on POD 8 and those who receive a 6th dose will be administered Thymoglobulin on POD 10. All groups will receive maintenance immunosuppression consisting of tacrolimus, mycophenolate mofetil, and corticosteroids (7 day corticosteroid taper to prednisone 5 mg daily).
|
Total
n=40 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
49.9 years
n=99 Participants
|
52.8 years
n=107 Participants
|
50.6 years
n=206 Participants
|
50.1 years
n=7 Participants
|
50.9 years
n=31 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
4 Participants
n=7 Participants
|
22 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
6 Participants
n=7 Participants
|
18 Participants
n=31 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=99 Participants
|
10 participants
n=107 Participants
|
10 participants
n=206 Participants
|
10 participants
n=7 Participants
|
40 participants
n=31 Participants
|
|
Pre-transplant diabetes mellitus
|
1 participants
n=99 Participants
|
4 participants
n=107 Participants
|
3 participants
n=206 Participants
|
1 participants
n=7 Participants
|
9 participants
n=31 Participants
|
|
Dialysis pre-transplant
|
9 participants
n=99 Participants
|
7 participants
n=107 Participants
|
8 participants
n=206 Participants
|
10 participants
n=7 Participants
|
34 participants
n=31 Participants
|
PRIMARY outcome
Timeframe: 6 monthsAntibody mediated rejection demonstrated to be due to, atleast in part, to anti-donor antibody at 6 months by Banff 97' criteria. Acute rejection IA - cases with significant interstitial infiltration (\>25% of parenchyma affected) and foci of moderate tubulitis (\>4 mononuclear cells/tubular cross section or group of 10 tubular cells). IB - cases with significant interstitial infiltration (\>25% of parenchyma affected) and foci of severe tubulitis (\>10 mononuclear cells/tubular cross section or group of 10 tubular cells) IIA - cases with mild to moderate intimal arteritis (v1) IIB - cases with server intimal arteritis comprising \>25% of the luminal area (v2) III - case with transmural arteritis and/or arterial fibrinoid change and necrosis of medical smooth muscle cells (v3 with accompanying lymphoctic inflammation)
Outcome measures
| Measure |
Rabbit Antithymocyte Globulin (RATG)
n=10 Participants
Thymoglobulin x 6 doses
|
RATG/Rituxan
n=10 Participants
Thymoglobulin x 5 doses + Rituximab 375mg/m2
|
RATG/Velcade
n=10 Participants
Thymoglobulin x 5 doses + Velcade
|
RATG/Rituxan/Velcade
n=10 Participants
Thymoglobulin x 4 doses + Rituximab 200mg/m2 + Velcade
|
|---|---|---|---|---|
|
Incidence of Acute Rejection (Banff '97) or Antibody Mediated Rejection
|
2 participants
|
0 participants
|
5 participants
|
3 participants
|
SECONDARY outcome
Timeframe: 6 monthsAntibody mediated rejection demonstrated to be due to, atleast in part, to anti-donor antibody at 6 months by Banff 97' criteria. Rejection due, at least in part, to documented anti-donor antibody ('suspicious for' if antibody not demonstrated); may coincide with categories 3, 4 and 5. Grade I. ATN-like - C4d+, minimal inflammation Grade II. Capillary- margination and/or thromboses, C4d+ Grade III. Arterial - v3, C4d+
Outcome measures
| Measure |
Rabbit Antithymocyte Globulin (RATG)
n=10 Participants
Thymoglobulin x 6 doses
|
RATG/Rituxan
n=10 Participants
Thymoglobulin x 5 doses + Rituximab 375mg/m2
|
RATG/Velcade
n=10 Participants
Thymoglobulin x 5 doses + Velcade
|
RATG/Rituxan/Velcade
n=10 Participants
Thymoglobulin x 4 doses + Rituximab 200mg/m2 + Velcade
|
|---|---|---|---|---|
|
Antibody-mediated Rejection by Banff '97 Criteria (Updated 2005)
|
1 participants
|
0 participants
|
3 participants
|
1 participants
|
SECONDARY outcome
Timeframe: 6 monthsAcute cellular rejection IA - cases with significant interstitial infiltration (\>25% of parenchyma affected) and foci of moderate tubulitis (\>4 mononuclear cells/tubular cross section or group of 10 tubular cells). IB - cases with significant interstitial infiltration (\>25% of parenchyma affected) and foci of severe tubulitis (\>10 mononuclear cells/tubular cross section or group of 10 tubular cells) IIA - cases with mild to moderate intimal arteritis (v1) IIB - cases with server intimal arteritis comprising \>25% of the luminal area (v2) III - case with transmural arteritis and/or arterial fibrinoid change and necrosis of medical smooth muscle cells (v3 with accompanying lymphoctic inflammation)
Outcome measures
| Measure |
Rabbit Antithymocyte Globulin (RATG)
n=10 Participants
Thymoglobulin x 6 doses
|
RATG/Rituxan
n=10 Participants
Thymoglobulin x 5 doses + Rituximab 375mg/m2
|
RATG/Velcade
n=10 Participants
Thymoglobulin x 5 doses + Velcade
|
RATG/Rituxan/Velcade
n=10 Participants
Thymoglobulin x 4 doses + Rituximab 200mg/m2 + Velcade
|
|---|---|---|---|---|
|
Acute Cellular Rejection by Banff '97 Criteria (Updated 2005)
|
1 participants
|
0 participants
|
1 participants
|
0 participants
|
SECONDARY outcome
Timeframe: 12 monthsPatient was still alive 12 months post study enrollment.
Outcome measures
| Measure |
Rabbit Antithymocyte Globulin (RATG)
n=10 Participants
Thymoglobulin x 6 doses
|
RATG/Rituxan
n=10 Participants
Thymoglobulin x 5 doses + Rituximab 375mg/m2
|
RATG/Velcade
n=10 Participants
Thymoglobulin x 5 doses + Velcade
|
RATG/Rituxan/Velcade
n=10 Participants
Thymoglobulin x 4 doses + Rituximab 200mg/m2 + Velcade
|
|---|---|---|---|---|
|
Patient Survival at 12 Months
|
10 participants
|
10 participants
|
10 participants
|
9 participants
|
SECONDARY outcome
Timeframe: 12 monthsPatient's allograft was still functioning at 12 months post study enrollment
Outcome measures
| Measure |
Rabbit Antithymocyte Globulin (RATG)
n=10 Participants
Thymoglobulin x 6 doses
|
RATG/Rituxan
n=10 Participants
Thymoglobulin x 5 doses + Rituximab 375mg/m2
|
RATG/Velcade
n=10 Participants
Thymoglobulin x 5 doses + Velcade
|
RATG/Rituxan/Velcade
n=10 Participants
Thymoglobulin x 4 doses + Rituximab 200mg/m2 + Velcade
|
|---|---|---|---|---|
|
Patient Allograft Survival at 12 Months
|
10 participants
|
10 participants
|
9 participants
|
9 participants
|
Adverse Events
Rabbit Antithymocyte Globulin (RATG)
Serious events: 2 serious events
Other events: 10 other events
Deaths: 0 deaths
RATG/Rituxan
Serious events: 4 serious events
Other events: 10 other events
Deaths: 0 deaths
RATG/Velcade
Serious events: 4 serious events
Other events: 10 other events
Deaths: 0 deaths
RATG/Rituxan/Velcade
Serious events: 2 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Rabbit Antithymocyte Globulin (RATG)
n=10 participants at risk
Rabbit Antithymocyte Globulin (RATG)
Rabbit Antithymocyte Globulin (RATG): RATG
|
RATG/Rituxan
n=10 participants at risk
Rabbit Antithymocyte Globulin (RATG)/Rituxan
RATG/Rituxan: RATG/Rituxan
RATG/Rituxan/Velcade: Rabbit Antithymocyte Globulin (RATG)/ Rituxan/ Velcade
|
RATG/Velcade
n=10 participants at risk
Rabbit Antithymocyte Globulin (RATG) /Velcade
RATG/Rituxan/Velcade: Rabbit Antithymocyte Globulin (RATG)/ Rituxan/ Velcade
|
RATG/Rituxan/Velcade
n=10 participants at risk
Rabbit Antithymocyte Globulin (RATG) / Rituxan / Velcade
RATG/Velcade: RATG/Velcade
|
|---|---|---|---|---|
|
Infections and infestations
CMV +/- Status
|
10.0%
1/10 • Number of events 1 • 12 months
|
0.00%
0/10 • 12 months
|
0.00%
0/10 • 12 months
|
10.0%
1/10 • Number of events 1 • 12 months
|
|
Infections and infestations
CMV Viremia
|
10.0%
1/10 • Number of events 1 • 12 months
|
30.0%
3/10 • Number of events 3 • 12 months
|
40.0%
4/10 • Number of events 4 • 12 months
|
20.0%
2/10 • Number of events 2 • 12 months
|
|
Infections and infestations
CMV Invasive Disease
|
0.00%
0/10 • 12 months
|
0.00%
0/10 • 12 months
|
10.0%
1/10 • Number of events 1 • 12 months
|
20.0%
2/10 • Number of events 2 • 12 months
|
|
Infections and infestations
EBV +/- Status
|
0.00%
0/10 • 12 months
|
0.00%
0/10 • 12 months
|
0.00%
0/10 • 12 months
|
0.00%
0/10 • 12 months
|
|
Infections and infestations
EBV Viremia
|
0.00%
0/10 • 12 months
|
0.00%
0/10 • 12 months
|
10.0%
1/10 • Number of events 1 • 12 months
|
0.00%
0/10 • 12 months
|
|
Infections and infestations
EBV-related disease / PTLD
|
0.00%
0/10 • 12 months
|
0.00%
0/10 • 12 months
|
0.00%
0/10 • 12 months
|
0.00%
0/10 • 12 months
|
|
Infections and infestations
BKV Viremia
|
0.00%
0/10 • 12 months
|
20.0%
2/10 • Number of events 2 • 12 months
|
30.0%
3/10 • Number of events 3 • 12 months
|
20.0%
2/10 • Number of events 2 • 12 months
|
|
Infections and infestations
BKV Nephropathy
|
0.00%
0/10 • 12 months
|
10.0%
1/10 • Number of events 1 • 12 months
|
10.0%
1/10 • Number of events 1 • 12 months
|
0.00%
0/10 • 12 months
|
|
Infections and infestations
Other Infections
|
20.0%
2/10 • Number of events 2 • 12 months
|
40.0%
4/10 • Number of events 4 • 12 months
|
40.0%
4/10 • Number of events 4 • 12 months
|
0.00%
0/10 • 12 months
|
Other adverse events
| Measure |
Rabbit Antithymocyte Globulin (RATG)
n=10 participants at risk
Rabbit Antithymocyte Globulin (RATG)
Rabbit Antithymocyte Globulin (RATG): RATG
|
RATG/Rituxan
n=10 participants at risk
Rabbit Antithymocyte Globulin (RATG)/Rituxan
RATG/Rituxan: RATG/Rituxan
RATG/Rituxan/Velcade: Rabbit Antithymocyte Globulin (RATG)/ Rituxan/ Velcade
|
RATG/Velcade
n=10 participants at risk
Rabbit Antithymocyte Globulin (RATG) /Velcade
RATG/Rituxan/Velcade: Rabbit Antithymocyte Globulin (RATG)/ Rituxan/ Velcade
|
RATG/Rituxan/Velcade
n=10 participants at risk
Rabbit Antithymocyte Globulin (RATG) / Rituxan / Velcade
RATG/Velcade: RATG/Velcade
|
|---|---|---|---|---|
|
Gastrointestinal disorders
CTCAE Grade 1 Nausea/Vomiting
|
30.0%
3/10 • Number of events 3 • 12 months
|
60.0%
6/10 • Number of events 6 • 12 months
|
20.0%
2/10 • Number of events 2 • 12 months
|
30.0%
3/10 • Number of events 3 • 12 months
|
|
Gastrointestinal disorders
CTCAE Grade 2 Nausea/Vomiting
|
0.00%
0/10 • 12 months
|
0.00%
0/10 • 12 months
|
30.0%
3/10 • Number of events 3 • 12 months
|
30.0%
3/10 • Number of events 3 • 12 months
|
|
Gastrointestinal disorders
CTCAE Grade 3 Nausea/Vomiting
|
30.0%
3/10 • Number of events 3 • 12 months
|
10.0%
1/10 • Number of events 1 • 12 months
|
10.0%
1/10 • Number of events 1 • 12 months
|
10.0%
1/10 • Number of events 1 • 12 months
|
|
Gastrointestinal disorders
CTCAE Grade 1 Diarrhea
|
20.0%
2/10 • Number of events 2 • 12 months
|
30.0%
3/10 • Number of events 3 • 12 months
|
30.0%
3/10 • Number of events 3 • 12 months
|
50.0%
5/10 • Number of events 5 • 12 months
|
|
Gastrointestinal disorders
CTCAE Grade 2 Diarrhea
|
20.0%
2/10 • Number of events 2 • 12 months
|
30.0%
3/10 • Number of events 3 • 12 months
|
30.0%
3/10 • Number of events 3 • 12 months
|
30.0%
3/10 • Number of events 3 • 12 months
|
|
Gastrointestinal disorders
CTCAE Grade 3 Diarrhea
|
0.00%
0/10 • 12 months
|
10.0%
1/10 • Number of events 1 • 12 months
|
20.0%
2/10 • Number of events 2 • 12 months
|
10.0%
1/10 • Number of events 1 • 12 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place