Trial Outcomes & Findings for A Trial of Two Steroid-Free Approaches Toward Mycophenolate Mofetil-Based Monotherapy Immunosuppression (NCT NCT00166712)
NCT ID: NCT00166712
Last Updated: 2015-10-26
Results Overview
The incidence of rejection is determined by the proportion of patients experiencing biopsy proven acute allograft rejection during the first 12 months post-transplant.
Recruitment status
TERMINATED
Study phase
PHASE4
Target enrollment
40 participants
Primary outcome timeframe
Within 12 months post kidney transplant
Results posted on
2015-10-26
Participant Flow
All patients were approached in the transplant clinic a Northwestern Memorial Hospital. Recruitment began April 2005 and ended April 2009.
Before being randomized (assigned to group) into Group 1 or Group 2, patients were screened based on inclusion/exclusion criteria (see Eligibility Criteria section). Randomization was decided before transplant surgery. Before re-randomization could begin (6 months after surgery), subjects could not be showing signs of organ rejection.
Participant milestones
| Measure |
Group 1: Alemtuzumab + TAC (Prograf) + MMF
Receive two doses of alemtuzumab (Campath-1H, 30mg) by intravenous (IV) infusion. One dose during kidney transplant surgery and the second dose on day 2 (post-surgery) to achieve peripheral T-cell depletion. IV glucocorticoids will be given prior to Campath administration to limit cytokine release syndrome in association with this monoclonal antibody. MMF on the day of surgery and continue taking it by mouth, twice daily. TAC started on the 1st day after surgery, and then taken by mouth twice daily.
|
Group 2: Alemtuzumab + Sirolimus + MMF
Sirolimus will be taken by mouth before transplant surgery and will continue taking once daily after surgery. Group 2 will also receive 2 doses of Alemtuzumab: one during surgery and the second will be given on the second day after surgery. Mycophenolate mofetil will be give on the day of surgery and twice daily, by mouth, as instructed by the doctor.
If subjects do not experience kidney rejection after 6 months after surgery, they will be weaned off of the sirolimus and continue taking the mycophenolate mofetil.
|
|---|---|---|
|
Overall Study
STARTED
|
24
|
16
|
|
Overall Study
Phase 1
|
22
|
12
|
|
Overall Study
Phase 2a
|
19
|
12
|
|
Overall Study
Phase 2b
|
3
|
0
|
|
Overall Study
Phase 3
|
0
|
0
|
|
Overall Study
COMPLETED
|
22
|
11
|
|
Overall Study
NOT COMPLETED
|
2
|
5
|
Reasons for withdrawal
| Measure |
Group 1: Alemtuzumab + TAC (Prograf) + MMF
Receive two doses of alemtuzumab (Campath-1H, 30mg) by intravenous (IV) infusion. One dose during kidney transplant surgery and the second dose on day 2 (post-surgery) to achieve peripheral T-cell depletion. IV glucocorticoids will be given prior to Campath administration to limit cytokine release syndrome in association with this monoclonal antibody. MMF on the day of surgery and continue taking it by mouth, twice daily. TAC started on the 1st day after surgery, and then taken by mouth twice daily.
|
Group 2: Alemtuzumab + Sirolimus + MMF
Sirolimus will be taken by mouth before transplant surgery and will continue taking once daily after surgery. Group 2 will also receive 2 doses of Alemtuzumab: one during surgery and the second will be given on the second day after surgery. Mycophenolate mofetil will be give on the day of surgery and twice daily, by mouth, as instructed by the doctor.
If subjects do not experience kidney rejection after 6 months after surgery, they will be weaned off of the sirolimus and continue taking the mycophenolate mofetil.
|
|---|---|---|
|
Overall Study
Death
|
0
|
1
|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
2
|
|
Overall Study
Physician Decision
|
0
|
2
|
Baseline Characteristics
A Trial of Two Steroid-Free Approaches Toward Mycophenolate Mofetil-Based Monotherapy Immunosuppression
Baseline characteristics by cohort
| Measure |
Group 1: Alemtuzumab + TAC (Prograf) + MMF
n=24 Participants
Receive two doses of alemtuzumab (Campath-1H, 30mg) by intravenous (IV) infusion. One dose during kidney transplant surgery and the second dose on day 2 (post-surgery) to achieve peripheral T-cell depletion. IV glucocorticoids will be given prior to Campath administration to limit cytokine release syndrome in association with this monoclonal antibody. MMF on the day of surgery and continue taking it by mouth, twice daily. TAC (Prograf) started on the 1st day after surgery, and then taken by mouth twice daily.
|
Group 2: Alemtuzumab + Sirolimus + MMF
n=16 Participants
Sirolimus will be taken by mouth before transplant surgery and will continue taking once daily after surgery. Group 2 will also receive 2 doses of Alemtuzumab: one during surgery and the second will be given on the second day after surgery. Mycophenolate mofetil will be give on the day of surgery and twice daily, by mouth, as instructed by the doctor.
If subjects do not experience kidney rejection after 6 months after surgery, they will be weaned off of the sirolimus and continue taking the mycophenolate mofetil.
|
Total
n=40 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
24 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
46.45833 years
STANDARD_DEVIATION 11.25584 • n=5 Participants
|
48.125 years
STANDARD_DEVIATION 11.51738 • n=7 Participants
|
47.125 years
STANDARD_DEVIATION 11.24366 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
24 participants
n=5 Participants
|
16 participants
n=7 Participants
|
40 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Within 12 months post kidney transplantPopulation: 33 total subjects reached the 12 month participation mark.
The incidence of rejection is determined by the proportion of patients experiencing biopsy proven acute allograft rejection during the first 12 months post-transplant.
Outcome measures
| Measure |
Groups
n=22 Participants
Evaluated for rejection of their transplanted kidney with a biopsy.
|
Group 2
n=11 Participants
Evaluated for rejection of their transplanted kidney with a biopsy.
|
|---|---|---|
|
The Incidence of Biopsy-proven Acute Allograft Rejection During the First 12 Months of Transplant.
|
4 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: Months 6-12 post-transplantPopulation: Study was terminated due to efficacy and there is no data was collected for this outcome measure.
The diagnosis of rejection will be based on clinical symptoms and signs, laboratory tests, and confirmed by core renal allograft biopsy.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At 12 months post-transplantPopulation: Study was stopped due to efficacy and no data was collected for this outcome measure.
Laboratory tests for renal function include creatinine or iothalamate glomerular filtration rate (GFR).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At 6 & 9 months post-transplantPopulation: Study was stopped due to efficacy and no data was collected for this outcome measure.
The proportion of subjects for both groups determine this measure: 1) Patients in tacrolimus arm who do not experience acute rejection and demonstrate evidence of donor specific hyporesonsiveness at 9 months post-transplant (those staying on TAC+MMF) or 3 months post-convertion (converted from TAC+MMF to Sirolimus+MMF) will be weaned to MMF monotherapy; 2) Those in the sirolimus+MMF arm who do not experience acute rejection and demonstrate evidence of donor specific hyporesponsiveness at 6 months post-transplant will be weaned to MMF monotherapy.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At 6 & 12 months post-transplantPopulation: Study was stopped due to efficacy and no data was collected for this outcome measure.
Outcome measures
Outcome data not reported
Adverse Events
Group 1: Alemtuzumab + TAC + MMF
Serious events: 4 serious events
Other events: 16 other events
Deaths: 0 deaths
Group 2: Alemtuzumab + Sirolimus + MMF
Serious events: 4 serious events
Other events: 14 other events
Deaths: 0 deaths
Group 1: Post-conversion to Sirolimus
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Group 1: Alemtuzumab + TAC + MMF
n=24 participants at risk
Receive two doses of alemtuzumab (Campath-1H, 30mg) by intravenous (IV) infusion. One dose during kidney transplant surgery and the second dose on day 2 (post-surgery) to achieve peripheral T-cell depletion. IV glucocorticoids will be given prior to Campath administration to limit cytokine release syndrome in association with this monoclonal antibody. MMF on the day of surgery and continue taking it by mouth, twice daily. TAC started on the 1st day after surgery, and then taken by mouth twice daily.
|
Group 2: Alemtuzumab + Sirolimus + MMF
n=16 participants at risk
Sirolimus will be taken by mouth before transplant surgery and will continue taking once daily after surgery. Group 2 will also receive 2 doses of Alemtuzumab: one during surgery and the second will be given on the second day after surgery. Mycophenolate mofetil will be give on the day of surgery and twice daily, by mouth, as instructed by the doctor.
If subjects do not experience kidney rejection after 6 months after surgery, they will be weaned off of the sirolimus and continue taking the mycophenolate mofetil.
|
Group 1: Post-conversion to Sirolimus
n=3 participants at risk
After conversion to Sirolimus, if no rejection of transplanted kidney within 9 months post-transplant, will be weaned off Sirolimus.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Deep vein thrombosis
|
0.00%
0/24
|
6.2%
1/16
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary emboli
|
4.2%
1/24
|
0.00%
0/16
|
0.00%
0/3
|
|
Cardiac disorders
Hypertension/respiratory distress post kidney biospy
|
4.2%
1/24
|
0.00%
0/16
|
0.00%
0/3
|
|
Infections and infestations
CMV
|
4.2%
1/24
|
0.00%
0/16
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Abdominal hernia
|
0.00%
0/24
|
6.2%
1/16
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Would dishiscence
|
0.00%
0/24
|
6.2%
1/16
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Shortness of breath
|
4.2%
1/24
|
0.00%
0/16
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Community aquired pneumonia
|
0.00%
0/24
|
6.2%
1/16
|
0.00%
0/3
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/24
|
0.00%
0/16
|
33.3%
1/3
|
Other adverse events
| Measure |
Group 1: Alemtuzumab + TAC + MMF
n=24 participants at risk
Receive two doses of alemtuzumab (Campath-1H, 30mg) by intravenous (IV) infusion. One dose during kidney transplant surgery and the second dose on day 2 (post-surgery) to achieve peripheral T-cell depletion. IV glucocorticoids will be given prior to Campath administration to limit cytokine release syndrome in association with this monoclonal antibody. MMF on the day of surgery and continue taking it by mouth, twice daily. TAC started on the 1st day after surgery, and then taken by mouth twice daily.
|
Group 2: Alemtuzumab + Sirolimus + MMF
n=16 participants at risk
Sirolimus will be taken by mouth before transplant surgery and will continue taking once daily after surgery. Group 2 will also receive 2 doses of Alemtuzumab: one during surgery and the second will be given on the second day after surgery. Mycophenolate mofetil will be give on the day of surgery and twice daily, by mouth, as instructed by the doctor.
If subjects do not experience kidney rejection after 6 months after surgery, they will be weaned off of the sirolimus and continue taking the mycophenolate mofetil.
|
Group 1: Post-conversion to Sirolimus
n=3 participants at risk
After conversion to Sirolimus, if no rejection of transplanted kidney within 9 months post-transplant, will be weaned off Sirolimus.
|
|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Chest Pain
|
4.2%
1/24
|
0.00%
0/16
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Shingles
|
0.00%
0/24
|
6.2%
1/16
|
0.00%
0/3
|
|
Renal and urinary disorders
Severe cellular rejection
|
4.2%
1/24
|
0.00%
0/16
|
0.00%
0/3
|
|
Renal and urinary disorders
Antibody mediated rejection
|
4.2%
1/24
|
0.00%
0/16
|
33.3%
1/3
|
|
General disorders
Right upper quadrant pain post conversion to rapamune
|
4.2%
1/24
|
0.00%
0/16
|
0.00%
0/3
|
|
Cardiac disorders
Orthostatic hypertension
|
4.2%
1/24
|
0.00%
0/16
|
0.00%
0/3
|
|
Gastrointestinal disorders
Diarrhea
|
4.2%
1/24
|
6.2%
1/16
|
0.00%
0/3
|
|
Renal and urinary disorders
Pyelonephritis
|
0.00%
0/24
|
6.2%
1/16
|
0.00%
0/3
|
|
Blood and lymphatic system disorders
Hyperkalemia
|
4.2%
1/24
|
0.00%
0/16
|
33.3%
1/3
|
|
Renal and urinary disorders
Bladder spasms
|
4.2%
1/24
|
0.00%
0/16
|
0.00%
0/3
|
|
Infections and infestations
Positive sputum culture
|
0.00%
0/24
|
6.2%
1/16
|
0.00%
0/3
|
|
Renal and urinary disorders
Urinary tract infection
|
8.3%
2/24
|
0.00%
0/16
|
0.00%
0/3
|
|
Gastrointestinal disorders
Nausea, vomiting, diarrhea
|
4.2%
1/24
|
0.00%
0/16
|
0.00%
0/3
|
|
Infections and infestations
Cellulitis of AV fistula repair site
|
0.00%
0/24
|
6.2%
1/16
|
0.00%
0/3
|
|
Renal and urinary disorders
Fluid collection around kidney
|
0.00%
0/24
|
6.2%
1/16
|
0.00%
0/3
|
|
General disorders
Abdominal pain
|
0.00%
0/24
|
12.5%
2/16
|
0.00%
0/3
|
|
Infections and infestations
Fever
|
16.7%
4/24
|
18.8%
3/16
|
0.00%
0/3
|
|
Renal and urinary disorders
Acute allograft rejection
|
4.2%
1/24
|
18.8%
3/16
|
0.00%
0/3
|
Additional Information
Joseph Leventhal, MD, PhD, Associate Professor
Comprehensive Transplant Center, Northwestern University
Phone: (312) 695-1703
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place