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Kidney TransplantationPhase 1/2NCT00078559

Combination Immunosuppressive Therapy to Prevent Kidney Transplant Rejection in Adults

A Phase 1/2 study testing Alemtuzumab, Sirolimus and Tacrolimus in people with Kidney Transplantation and Kidney Disease, run by University of Wisconsin, Madison at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Kidney Transplantation, Kidney Disease
What is being tested?
Alemtuzumab, Sirolimus and Tacrolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
Nov 2003to Feb 2010
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 25Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Wisconsin - Department of Medicine

    Madison, Wisconsin, 53792-1735

Other trials in United States

About this study

Official title: 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.

Read the detailed description

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.

Being tested
Alemtuzumab, Sirolimus, Tacrolimus, Kidney transplant, Methylprednisolone (or equivalent)
Keywords
Immunosuppression, Renal Failure
Medical subject headings
Kidney Diseases, Renal Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AlemtuzumabDrug

    30mg intravenous infusion on days 0 (transplant), 1, and 2

  • SirolimusDrug

    2mg/day orally within 24-48 hrs post-transplant, and adjusted to achieve blood levels of 8-12 ng/mL for 1 year

  • TacrolimusDrug

    2mg orally twice daily, on days 1-60

  • Kidney transplantProcedure or surgery

    Kidney transplant with primary cadaveric or non-HLA-identical living donor kidney (0-3 HLA-antigen mismatch)

  • Methylprednisolone (or equivalent)Drug

    250 mg intravenous infusion 60 minutes prior to first dose of alemtuzumab

  • AcetaminophenDrug

    650 mg may be given 30-60 minutes prior to start of each infusion of alemtuzumab to prevent infusion related side effects such as fever, skin rash and pruritis

  • DiphenhydramineDrug

    25 mg may be given 30-60 minutes prior to start of each infusion of alemtuzumab to prevent infusion related side effects such as fever, skin rash and pruritis

  • Trimethoprim (TMP)/Sulfa (Bactrim, Septra)Drug

    1 double strength tablet 3 times a week from day 1 through 1 year post-transplant.

  • ValgancyclovirDrug

    Given orally beginning on day 1 for up to 10 days post-transplant (until participant discharged from hospital if prior to 10 days). Dose adjusted based on participants calculated creatinine clearance

  • AcyclovirDrug

    400 mg orally twice daily or 800 mg orally four times daily (dose adjusted based on calculated creatinine clearance and cytomegalovirus antibody serologic status of donor and recipient) for a minimum of 3 months starting when valganciclovir discontinued.

  • PentamidineDrug

    300 mg/6 mL inhalation therapy once monthly for a total of 6 treatments. First treatment given within one week post-transplant for participants with a known allergy or intolerance to sulfa

  • ClotrimazoleDrug

    10 mg orally four times daily for a minimum of 3 months post-transplant (subjects take either clotrimazole or nystatin, not both)

  • NystatinDrug

    500,000 units/5 mL orally four times daily for a minimum of 3 months post-transplant (subjects take either nystatin or clotrimazole, not both)

Study groups in NCT00078559
Study groupRoleWhat they receive
AlemtuzumabExperimentalNot described
Receives: Drug: Alemtuzumab; Drug: Sirolimus; Drug: Tacrolimus; Procedure: Kidney transplant; Drug: Methylprednisolone (or equivalent); Drug: Acetaminophen; Drug: Diphenhydramine; Drug: Trimethoprim (TMP)/Sulfa (Bactrim, Septra); Drug: Valgancyclovir; Drug: Acyclovir; Drug: Pentamidine; Drug: Clotrimazole; Drug: Nystatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    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

    Measured: Four years post-transplant

Secondary outcomes (13)

  1. 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

    Measured: Transplantation to end of study (up to four years post-transplant)

  2. 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

    Measured: Initiation of sirolimus to end of study (up to four years post-transplant)

  3. 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

    Measured: Transplantation to acute rejection (up to four years post-transplantation)

  4. 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

    Measured: Transplantation to acute rejection (up to one year post-transplant)

  5. Number of Deaths Stratified by Sirolimus Withdrawal Status

    Participants who died during the study, all cause(s)

    Measured: Transplantation to Death (up to four years post-transplant)

  6. 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

    Measured: Transplantation to Graft Loss (up to four years post-transplantation)

  7. Number of Severe Acute Rejections Stratified by Sirolimus Withdrawal Status

    Participants who experienced severe acute rejections[1] during study

    1. 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]
    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

    Measured: Transplantation to severe acute rejection (up to four years post-transplantation)

  8. 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

    Measured: Transplantation to acute rejection (up to four years post-transplantation)

  9. Number of Alemtuzumab Associated Adverse Events, Stratified by Sirolimus Withdrawal Status

    Measured: Transplantation to end of study (up to four years post-transplant)

  10. Number of Tacrolimus Associated Adverse Events, Stratified by Sirolimus Withdrawal Status

    Measured: Transplantation to end of study (up to four years post-transplant)

  11. Number of Sirolimus Associated Adverse Events, Stratified by Sirolimus Withdrawal Status

    Measured: Transplantation to end of study (up to four years post-transplant)

  12. Number of Side Effects of Conventional Immunosuppression, Stratified by Withdrawal Status

    Side effects of conventional immunosuppression include increased body weight and hypertension

    Measured: Transplantation to end of study (up to four years post-transplant)

  13. 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

    Measured: Transplantation to end of study (up to four years post-transplant)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Mar 2004 (estimated)
  2. Study startNov 2003
  3. Primary completionFeb 2010
  4. Study completionFeb 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00078559
Sponsor's protocol ID
DAIT ITN013ST
Other IDs
H-2003-0435
Status last verified
May 2018
First submitted
1 Mar 2004
Last updated
29 Jun 2018
Data monitoring committee
Yes

Publications

  • First MR. Tacrolimus based immunosuppression. J Nephrol. 2004 Nov-Dec;17 Suppl 8:S25-31.

    PubMed 15599882

  • Gourishankar S, Turner P, Halloran P. New developments in immunosuppressive therapy in renal transplantation. Expert Opin Biol Ther. 2002 Jun;2(5):483-501. doi: 10.1517/14712598.2.5.483.

    PubMed 12079485

  • 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. doi: 10.1111/j.1600-6143.2005.00822.x.

    PubMed 15888040

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Alemtuzumab, Sirolimus and Tacrolimus in people with Kidney Transplantation and Kidney Disease, run by University of Wisconsin, Madison at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Jul 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Acute Rejections in All Enrolled Participants (time frame: Four years post-transplant). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00078559, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2018.

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