Combination Immunosuppressive Therapy to Prevent Kidney Transplant Rejection in Adults
| Status: | Completed |
|---|---|
| Conditions: | Renal Impairment / Chronic Kidney Disease |
| Therapuetic Areas: | Nephrology / Urology |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 7/1/2018 |
| Start Date: | November 2003 |
| End Date: | February 2010 |
The Use of Campath-1H, Tacrolimus, and Sirolimus Followed by Sirolimus Withdrawal in Renal Transplant Patients
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.
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.
Drugs that suppress the immune system, such as sirolimus and tacrolimus, have contributed to
increased success of transplantation. However, to prevent organ rejection, transplant
recipients need to take immunosuppressive drugs for the rest of their lives, and these drugs
make patients more susceptible to infection, endangering their health and survival. Regimens
that are less toxic to or can eventually be withdrawn from transplant recipients are needed.
Alemtuzumab is a monoclonal antibody that binds to and depletes excess T cells in the bone
marrow of leukemia patients. This study will determine the effects of intravenous alemtuzumab
and oral sirolimus and tacrolimus after kidney transplantation. The study will also evaluate
this regimen's potential to allow eventual discontinuation of components of long-term
immunosuppressive therapy.
This study will last up to 4 years. Participants will undergo kidney transplantation on Day 0
and will receive intravenous doses of alemtuzumab, acetaminophen, and diphenhydramine on Days
0, 1, and 2, as well as methylprednisolone on Day 0. After transplant, patients will receive
up to 10 days of valganciclovir or acyclovir. Participants will take tacrolimus daily by
mouth for at least 60 days after transplant and sirolimus daily by mouth for at least 12
months after transplant. As part of opportunistic infection (OI) prophylaxis, participants
will also take sulfamethoxazole-trimethoprim by mouth 3 times a week, valganciclovir or
acyclovir for up to 10 days post-transplant, and clotrimazole or nystatin by mouth for at
least 3 months post-transplant.
There will be a minimum of 62 study visits spread out over 4 years after transplant. Vital
signs measurement, adverse event and OI reporting, medication history, physical exam, and
blood collection will occur at selected visits. Sirolimus withdrawal will begin when a
participant meets certain study criteria. The withdrawal process will occur over a minimum of
3 months at an approximate rate of 33% of the pre-withdrawal dose per month. Participants
eligible for sirolimus withdrawal will undergo several kidney biopsies, including one 2 weeks
prior to the start of withdrawal, 6 and 12 months after completion of withdrawal, 1 year
after study enrollment, and annually thereafter.
increased success of transplantation. However, to prevent organ rejection, transplant
recipients need to take immunosuppressive drugs for the rest of their lives, and these drugs
make patients more susceptible to infection, endangering their health and survival. Regimens
that are less toxic to or can eventually be withdrawn from transplant recipients are needed.
Alemtuzumab is a monoclonal antibody that binds to and depletes excess T cells in the bone
marrow of leukemia patients. This study will determine the effects of intravenous alemtuzumab
and oral sirolimus and tacrolimus after kidney transplantation. The study will also evaluate
this regimen's potential to allow eventual discontinuation of components of long-term
immunosuppressive therapy.
This study will last up to 4 years. Participants will undergo kidney transplantation on Day 0
and will receive intravenous doses of alemtuzumab, acetaminophen, and diphenhydramine on Days
0, 1, and 2, as well as methylprednisolone on Day 0. After transplant, patients will receive
up to 10 days of valganciclovir or acyclovir. Participants will take tacrolimus daily by
mouth for at least 60 days after transplant and sirolimus daily by mouth for at least 12
months after transplant. As part of opportunistic infection (OI) prophylaxis, participants
will also take sulfamethoxazole-trimethoprim by mouth 3 times a week, valganciclovir or
acyclovir for up to 10 days post-transplant, and clotrimazole or nystatin by mouth for at
least 3 months post-transplant.
There will be a minimum of 62 study visits spread out over 4 years after transplant. Vital
signs measurement, adverse event and OI reporting, medication history, physical exam, and
blood collection will occur at selected visits. Sirolimus withdrawal will begin when a
participant meets certain study criteria. The withdrawal process will occur over a minimum of
3 months at an approximate rate of 33% of the pre-withdrawal dose per month. Participants
eligible for sirolimus withdrawal will undergo several kidney biopsies, including one 2 weeks
prior to the start of withdrawal, 6 and 12 months after completion of withdrawal, 1 year
after study enrollment, and annually thereafter.
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
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