Kidney Transplantation Clinical Trial
Official title:
The Use of Campath-1H, Tacrolimus, and Sirolimus Followed by Sirolimus Withdrawal in Renal Transplant Patients
Verified date | May 2018 |
Source | University of Wisconsin, Madison |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Transplant rejection occurs when a patient's body does not recognize the new organ and
attacks it. Patients who have kidney transplants must take drugs to prevent transplant
rejection. Alemtuzumab is a man-made antibody used to treat certain blood disorders. The
purpose of this study is to test the safety and effectiveness of using alemtuzumab in
combination with two other drugs, sirolimus and tacrolimus, to prevent organ rejection after
kidney transplantation. This study will also test whether this combination of medications
will allow patients to eventually stop taking antirejection medications entirely.
Study hypothesis: A new strategy of immunosuppression using alemtuzumab, tacrolimus, and
sirolimus for human renal transplantation will permit a step-wise withdrawal from
immunosuppressive drugs.
Status | Completed |
Enrollment | 10 |
Est. completion date | February 2010 |
Est. primary completion date | February 2010 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility |
Inclusion Criteria - Kidney transplant with primary cadaveric or non-Human Leukocyte Antigen (HLA)-identical living donor kidney (0-3 HLA-antigen mismatch) - Receiving only a kidney and no other organs - Able to take medications by mouth - Willing to use acceptable methods of contraception Exclusion Criteria - Received HLA-identical living-donor kidney transplant - HLA-antigen mismatch greater than 3 - Panel reactive antibody (PRA) value greater than 10% at any time prior to enrollment - Received a non-heart-beating donor allograft - Received a kidney from a donor who is greater than 60 years of age - End-stage Renal Disease (ESRD) due to Focal Segmental Glomulerosclerosis (FSGS) - Previous kidney transplant - Received multiorgan transplant - Concomitant systemic corticosteroid therapy for other medical diseases - Known hypersensitivity to alemtuzumab, tacrolimus, methylprednisolone, or sirolimus - Human Immunodeficiency Virus (HIV) infected - Hepatitis C virus infected - Positive for hepatitis B surface antigen - Received dual or en-bloc pediatric kidneys - Anti-human Globulin (AHG) or T cell crossmatch positive - Investigational drug within 6 weeks of study entry - Known clinically significant cardiovascular or cerebrovascular disease - Previous or current history of cancer or lymphoma. Patients with adequately treated basal or squamous cell skin carcinoma are not excluded. - Clinically significant coagulopathy or a requirement for chronic anti-coagulation therapy precluding biopsy - Cytomegalovirus (CMV)-negative recipient, if received kidney is from a CMV-positive donor - History of a psychological illness or condition that, in the opinion of the investigator, may interfere with the study - Graves disease. Patients who have been previously adequately treated with radioiodine ablative therapy are not excluded. - Active systemic infections - Platelets less than 100,000 cells/mm^3 at study entry - Pregnant or breastfeeding |
Country | Name | City | State |
---|---|---|---|
United States | University of Wisconsin - Department of Medicine | Madison | Wisconsin |
Lead Sponsor | Collaborator |
---|---|
University of Wisconsin, Madison | Immune Tolerance Network (ITN) |
United States,
First MR. Tacrolimus based immunosuppression. J Nephrol. 2004 Nov-Dec;17 Suppl 8:S25-31. Review. — View Citation
Gourishankar S, Turner P, Halloran P. New developments in immunosuppressive therapy in renal transplantation. Expert Opin Biol Ther. 2002 Jun;2(5):483-501. Review. — View Citation
Watson CJ, Bradley JA, Friend PJ, Firth J, Taylor CJ, Bradley JR, Smith KG, Thiru S, Jamieson NV, Hale G, Waldmann H, Calne R. Alemtuzumab (CAMPATH 1H) induction therapy in cadaveric kidney transplantation--efficacy and safety at five years. Am J Transplant. 2005 Jun;5(6):1347-53. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of Acute Rejections in All Enrolled Participants | Number of acute rejections[1] in all enrolled subjects from the time of transplantation to the end of the trial (four years post-transplant) Acute rejection is defined as a biopsy-proven rejection: a renal biopsy demonstrates acute cellular or humoral rejection of Banff[2] Grade 1B or greater; or presumed rejection in the absence of biopsy-proven rejection, the participant is treated for an unexplained 20% increase in serum creatinine. Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999 |
Four years post-transplant | |
Secondary | Number of Acute Rejections in All Enrolled Participants Following Sirolimus Withdrawal | Following sirolimus withdrawal, the number of acute rejections[1] in all enrolled participants 1] Acute rejection is defined as a biopsy-proven rejection: a renal biopsy demonstrates acute cellular or humoral rejection of Banff[2] Grade 1B or greater; or presumed rejection in the absence of biopsy-proven rejection, the participant is treated for an unexplained 20% increase in serum creatinine. [2] Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999 |
Transplantation to end of study (up to four years post-transplant) | |
Secondary | Number of Acute Rejections Between Initiation of Sirolimus Withdrawal and End of Study | Acute rejections[1] between initiation of sirolimus withdrawal and end of study 1] Acute rejection is defined as a biopsy-proven rejection: a renal biopsy demonstrates acute cellular or humoral rejection of Banff[2] Grade 1B or greater; or presumed rejection in the absence of biopsy-proven rejection, the participant is treated for an unexplained 20% increase in serum creatinine. [2] Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999 |
Initiation of sirolimus to end of study (up to four years post-transplant) | |
Secondary | Time From Transplantation to Acute Rejection in Participants for Whom Sirolimus Withdrawal Was Not Initiated | Time (days) to acute rejection[1] for participants where sirolimus was not initiated 1] Acute rejection is defined as a biopsy-proven rejection: a renal biopsy demonstrates acute cellular or humoral rejection of Banff[2] Grade 1B or greater; or presumed rejection in the absence of biopsy-proven rejection, the participant is treated for an unexplained 20% increase in serum creatinine. [2] Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999 |
Transplantation to acute rejection (up to four years post-transplantation) | |
Secondary | Time From Transplantation to Acute Rejection in Participants for Whom Acute Rejection Occurred During the 1 Year Post-transplant Period | Time (days) to acute rejection[1] for participants occurring during the year following transplantation 1] Acute rejection is defined as a biopsy-proven rejection: a renal biopsy demonstrates acute cellular or humoral rejection of Banff[2] Grade 1B or greater; or presumed rejection in the absence of biopsy-proven rejection, the participant is treated for an unexplained 20% increase in serum creatinine. [2] Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999 |
Transplantation to acute rejection (up to one year post-transplant) | |
Secondary | Number of Deaths Stratified by Sirolimus Withdrawal Status | Participants who died during the study, all cause(s) | Transplantation to Death (up to four years post-transplant) | |
Secondary | Number of Participants Who Experienced Graft Loss Stratified by Sirolimus Withdrawal Status | Participants who experienced graft loss[1] during study [1]Graft loss is defined as the institution of chronic dialysis (at least 6 consecutive weeks, excluding participants with delayed graft function), transplant nephrectomy, or retransplantation |
Transplantation to Graft Loss (up to four years post-transplantation) | |
Secondary | Number of Severe Acute Rejections Stratified by Sirolimus Withdrawal Status | Participants who experienced severe acute rejections[1] during study Severe acute rejection is defined as that which requires treatment with anti-lymphocyte antibody or is histologically evaluated as Type IIA or greater using the Banff 1997 criteria[2] Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999 |
Transplantation to severe acute rejection (up to four years post-transplantation) | |
Secondary | Number of Participants Requiring Anti-lymphocyte Therapy for an Acute Rejection, Stratified by Sirolimus Withdrawal Status | Participants who experienced acute rejection[1] during study which required anti-lymphocyte (OKT3, ATG) therapy 1] Acute rejection is defined as a biopsy-prove rejection: a renal biopsy demonstrates acute cellular or humoral rejection of Banff[2] Grade 1B or greater; or presumed rejection in the absence of biopsy-proven rejection, the participant is treated for an unexplained 20% increase in serum creatinine. [2] Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999 |
Transplantation to acute rejection (up to four years post-transplantation) | |
Secondary | Number of Alemtuzumab Associated Adverse Events, Stratified by Sirolimus Withdrawal Status | Transplantation to end of study (up to four years post-transplant) | ||
Secondary | Number of Tacrolimus Associated Adverse Events, Stratified by Sirolimus Withdrawal Status | Transplantation to end of study (up to four years post-transplant) | ||
Secondary | Number of Sirolimus Associated Adverse Events, Stratified by Sirolimus Withdrawal Status | Transplantation to end of study (up to four years post-transplant) | ||
Secondary | Number of Side Effects of Conventional Immunosuppression, Stratified by Withdrawal Status | Side effects of conventional immunosuppression include increased body weight and hypertension | Transplantation to end of study (up to four years post-transplant) | |
Secondary | Change in Renal Function as Measured by Serum Creatinine, Stratified by Withdrawal Status | Mean change from transplantation to Month 48 in serum creatinine. Normal serum creatinine range is from 0.7 - 1.4 mg/dL. In a transplant population, starting serum creatinine is higher than normal range. A negative change indicates better renal function | Transplantation to end of study (up to four years post-transplant) |
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