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Randomized Trial of Induction Therapies in High Immunological Risk Kidney Transplant Recipients

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ClinicalTrials.gov Identifier: NCT00782821
Recruitment Status : Completed
First Posted : October 31, 2008
Results First Posted : January 20, 2016
Last Update Posted : January 20, 2016
Sponsor:
Collaborators:
Millennium Pharmaceuticals, Inc.
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
E. Steve Woodle, University of Cincinnati

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Condition Kidney Transplantation
Interventions Drug: Rabbit Antithymocyte Globulin
Drug: Velcade
Drug: Rituxan
Enrollment 40
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Rabbit Antithymocyte Globulin (rATG) RATG/Rituxan RATG/Velcade RATG/Rituxan/Velcade
Hide Arm/Group Description

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).

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).

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.

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.
Period Title: Overall Study
Started 10 10 10 10
Completed 10 10 9 8
Not Completed 0 0 1 2
Arm/Group Title Rabbit Antithymocyte Globulin (RATG) RATG/Rituxan RATG/Velcade RATG/Rituxan/Velcade Total
Hide Arm/Group Description 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).

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).

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).

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 of all reporting groups
Overall Number of Baseline Participants 10 10 10 10 40
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 10 participants 10 participants 10 participants 10 participants 40 participants
49.9
(46.3 to 53.8)
52.8
(45.6 to 62.7)
50.6
(34.5 to 63.3)
50.1
(45.3 to 56.9)
50.9
(34.5 to 63.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 10 participants 10 participants 40 participants
Female
5
  50.0%
5
  50.0%
8
  80.0%
4
  40.0%
22
  55.0%
Male
5
  50.0%
5
  50.0%
2
  20.0%
6
  60.0%
18
  45.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 10 participants 10 participants 10 participants 10 participants 40 participants
10 10 10 10 40
Pre-transplant diabetes mellitus  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 10 participants 10 participants 40 participants
1 4 3 1 9
Dialysis pre-transplant  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 10 participants 10 participants 40 participants
9 7 8 10 34
1.Primary Outcome
Title Incidence of Acute Rejection (Banff ’97) or Antibody Mediated Rejection
Hide Description

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)

Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Rabbit Antithymocyte Globulin (RATG) RATG/Rituxan RATG/Velcade RATG/Rituxan/Velcade
Hide Arm/Group Description:
Thymoglobulin x 6 doses
Thymoglobulin x 5 doses + Rituximab 375mg/m2
Thymoglobulin x 5 doses + Velcade
Thymoglobulin x 4 doses + Rituximab 200mg/m2 + Velcade
Overall Number of Participants Analyzed 10 10 10 10
Measure Type: Number
Unit of Measure: participants
2 0 5 3
2.Secondary Outcome
Title Antibody-mediated Rejection by Banff '97 Criteria (Updated 2005)
Hide Description

Antibody 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+

Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Rabbit Antithymocyte Globulin (RATG) RATG/Rituxan RATG/Velcade RATG/Rituxan/Velcade
Hide Arm/Group Description:
Thymoglobulin x 6 doses
Thymoglobulin x 5 doses + Rituximab 375mg/m2
Thymoglobulin x 5 doses + Velcade
Thymoglobulin x 4 doses + Rituximab 200mg/m2 + Velcade
Overall Number of Participants Analyzed 10 10 10 10
Measure Type: Number
Unit of Measure: participants
1 0 3 1
3.Secondary Outcome
Title Acute Cellular Rejection by Banff '97 Criteria (Updated 2005)
Hide Description

Acute 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)

Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Rabbit Antithymocyte Globulin (RATG) RATG/Rituxan RATG/Velcade RATG/Rituxan/Velcade
Hide Arm/Group Description:
Thymoglobulin x 6 doses
Thymoglobulin x 5 doses + Rituximab 375mg/m2
Thymoglobulin x 5 doses + Bortezomib
Thymoglobulin x 4 doses + Rituximab 200mg/m2 + Bortezomib
Overall Number of Participants Analyzed 10 10 10 10
Measure Type: Number
Unit of Measure: participants
1 0 1 0
4.Secondary Outcome
Title Patient Survival at 12 Months
Hide Description Patient was still alive 12 months post study enrollment.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Rabbit Antithymocyte Globulin (RATG) RATG/Rituxan RATG/Velcade RATG/Rituxan/Velcade
Hide Arm/Group Description:
Thymoglobulin (RATG) x 6 doses (1.5mg/kg IV)
Thymoglobulin x 5 doses + Rituximab 375mg/m2
Thymoglobulin x 5 doses + Velcade
Thymoglobulin x 4 doses + Rituximab 200mg/m2 + Bortezomib
Overall Number of Participants Analyzed 10 10 10 10
Measure Type: Number
Unit of Measure: participants
10 10 10 9
5.Secondary Outcome
Title Patient Allograft Survival at 12 Months
Hide Description Patient's allograft was still functioning at 12 months post study enrollment
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Rabbit Antithymocyte Globulin (RATG) RATG/Rituxan RATG/Velcade RATG/Rituxan/Velcade
Hide Arm/Group Description:

Rabbit Antithymocyte Globulin (RATG)

Rabbit Antithymocyte Globulin (RATG): RATG

Rabbit Antithymocyte Globulin (RATG)/Rituxan

RATG/Rituxan: RATG/Rituxan

RATG/Rituxan/Velcade: Rabbit Antithymocyte Globulin (RATG)/ Rituxan/ Velcade

Rabbit Antithymocyte Globulin (RATG) /Velcade

RATG/Rituxan/Velcade: Rabbit Antithymocyte Globulin (RATG)/ Rituxan/ Velcade

Rabbit Antithymocyte Globulin (RATG) / Rituxan / Velcade

RATG/Velcade: RATG/Velcade

Overall Number of Participants Analyzed 10 10 10 10
Measure Type: Number
Unit of Measure: participants
10 10 9 9
Time Frame 12 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Rabbit Antithymocyte Globulin (RATG) RATG/Rituxan RATG/Velcade RATG/Rituxan/Velcade
Hide Arm/Group Description

Rabbit Antithymocyte Globulin (RATG)

Rabbit Antithymocyte Globulin (RATG): RATG

Rabbit Antithymocyte Globulin (RATG)/Rituxan

RATG/Rituxan: RATG/Rituxan

RATG/Rituxan/Velcade: Rabbit Antithymocyte Globulin (RATG)/ Rituxan/ Velcade

Rabbit Antithymocyte Globulin (RATG) /Velcade

RATG/Rituxan/Velcade: Rabbit Antithymocyte Globulin (RATG)/ Rituxan/ Velcade

Rabbit Antithymocyte Globulin (RATG) / Rituxan / Velcade

RATG/Velcade: RATG/Velcade

All-Cause Mortality
Rabbit Antithymocyte Globulin (RATG) RATG/Rituxan RATG/Velcade RATG/Rituxan/Velcade
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Rabbit Antithymocyte Globulin (RATG) RATG/Rituxan RATG/Velcade RATG/Rituxan/Velcade
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/10 (20.00%)      4/10 (40.00%)      4/10 (40.00%)      2/10 (20.00%)    
Infections and infestations         
CMV +/- Status  1  1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  1
CMV Viremia  1  1/10 (10.00%)  1 3/10 (30.00%)  3 4/10 (40.00%)  4 2/10 (20.00%)  2
CMV Invasive Disease  1  0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  1 2/10 (20.00%)  2
EBV +/- Status  1  0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0
EBV Viremia  1  0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0
EBV-related disease / PTLD  1  0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0
BKV Viremia  1  0/10 (0.00%)  0 2/10 (20.00%)  2 3/10 (30.00%)  3 2/10 (20.00%)  2
BKV Nephropathy  1  0/10 (0.00%)  0 1/10 (10.00%)  1 1/10 (10.00%)  1 0/10 (0.00%)  0
Other Infections * 1  2/10 (20.00%)  2 4/10 (40.00%)  4 4/10 (40.00%)  4 0/10 (0.00%)  0
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Rabbit Antithymocyte Globulin (RATG) RATG/Rituxan RATG/Velcade RATG/Rituxan/Velcade
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/10 (100.00%)      10/10 (100.00%)      10/10 (100.00%)      10/10 (100.00%)    
Gastrointestinal disorders         
CTCAE Grade 1 Nausea/Vomiting  1  3/10 (30.00%)  3 6/10 (60.00%)  6 2/10 (20.00%)  2 3/10 (30.00%)  3
CTCAE Grade 2 Nausea/Vomiting  1  0/10 (0.00%)  0 0/10 (0.00%)  0 3/10 (30.00%)  3 3/10 (30.00%)  3
CTCAE Grade 3 Nausea/Vomiting  1  3/10 (30.00%)  3 1/10 (10.00%)  1 1/10 (10.00%)  1 1/10 (10.00%)  1
CTCAE Grade 1 Diarrhea  1  2/10 (20.00%)  2 3/10 (30.00%)  3 3/10 (30.00%)  3 5/10 (50.00%)  5
CTCAE Grade 2 Diarrhea  1  2/10 (20.00%)  2 3/10 (30.00%)  3 3/10 (30.00%)  3 3/10 (30.00%)  3
CTCAE Grade 3 Diarrhea  1  0/10 (0.00%)  0 1/10 (10.00%)  1 2/10 (20.00%)  2 1/10 (10.00%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: E. Steve Woodle, MD
Organization: University of Cincinnati
Phone: 513-558-6001
Responsible Party: E. Steve Woodle, University of Cincinnati
ClinicalTrials.gov Identifier: NCT00782821     History of Changes
Other Study ID Numbers: X05274
First Submitted: October 29, 2008
First Posted: October 31, 2008
Results First Submitted: October 20, 2015
Results First Posted: January 20, 2016
Last Update Posted: January 20, 2016