Kidney Failure, ChronicPhase 2NCT00240994
Safety in Immunomodulatory Functions of Alemtuzumab (Campath) in Pediatric Kidney Transplantation Recipients
A Phase 2 study testing Alemtuzumab, Tacrolimus and Mycophenolate mofetil in people with Kidney Failure, Chronic and Kidney Transplantation, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 sites in United States.
Trial summary
The purpose of this study is to evaluate the safety of alemtuzumab after kidney transplantation as part of a multitherapy regimen to prevent kidney graft loss and death and to avoid steroids and chronic use of calcineurin inhibitors in pediatric renal transplant recipients 1 to 20 years of age. Read more about this study
- Who is it for?
- Ages 1 year to 20 years
- Conditions the study is for
- Kidney Failure, Chronic, Kidney Transplantation, Immunosuppression
- What is being tested?
- Alemtuzumab, Tacrolimus and Mycophenolate mofetil
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 4 sitesUnited States
- Study dates
- Jan 2005to Nov 2009
- Phase
- Phase 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 1 year to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Between the ages of 1 to 20 (prior to 21st birthday)
- End Stage Renal Disease
- Necessity of kidney transplant
- First kidney transplant received from a living donor
- A living kidney donor identified
- No known contraindications to therapy with alemtuzumab
Show all 10Show fewer
- Negative pregnancy test before study entry
- Willing to use approved methods of contraception for the duration of the study, 6 weeks after discontinuation of MMF, and 12 weeks after discontinuation of sirolimus
- Informed consent from participant, parent, or guardian
- Current vaccinations, including varicella-zoster (VZV) vaccine, before study enrollment
Who cannot join
- Recipient of a deceased donor kidney transplant
- Multiorgan transplant
- History of prior organ transplantation
- Participant sensitized to greater than 0% Panel Reactive Antibody (PRA) within 4 weeks before study enrollment. (If participant receives a blood transfusion status post PRA test, then the PRA must be repeated within 1 week of transplantation)
- Participants with human leukocyte antigen (HLA) identical living related donors
- History of primary focal segmented glomerulosclerosis
Show all 14Show fewer
- History of other disorders requiring continuous maintenance steroids or calcineurin inhibitors
- Active systemic infection at time of transplant
- History of malignancy
- Infected with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
- Contraindication to receive tacrolimus, sirolimus, MMF, or monoclonal antibody therapy
- Use of investigational drugs within 4 weeks before study enrollment
- Recipient of any licensed or investigational live attenuated vaccine(s) within 2 months before study enrollment
- Family history of high cholesterol
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Children's Hospital, Boston
Boston, Massachusetts, 02115
Children's Hospital, Philadelphia
Philadelphia, Pennsylvania, 19104
University of California, San Francisco
San Francisco, California, 94143-0116
Children's Hospital and Regional Medical Center, Seattle
Seattle, Washington, 98105
About this study
Official title: A Phase II Exploratory Study to Determine the Safety and Study the Immunomodulatory Functions of Induction Therapy With Campath, Combined With Chronic Immunosuppression With Mycophenolate Mofetil and Sirolimus
The purpose of this study is to evaluate the safety of alemtuzumab after kidney transplantation as part of a multitherapy regimen to prevent kidney graft loss and death and to avoid steroids and chronic use of calcineurin inhibitors in pediatric renal transplant recipients 1 to 20 years of age.
Read the detailed description
Kidney transplantation is widely considered to be the treatment of choice for children with End Stage Renal Disease (ESRD). Improvements in surgical techniques, donor selection, and immunosuppression practices, as well as the enhanced experience of specialized pediatric transplant teams, have all led to marked improvements in patient and kidney graft survival in infants and young children ages 1 to 10. However, young children now have more infections following transplant previously. Also, improved graft survival is not observed in pediatric renal transplant recipients 11 to 17 years of age. Some studies do indicate that the poor long term outcome of patient and kidney survival observed in this age group may be caused by noncompliance with immunosuppressive medications. Therefore, protocols that minimize the use of immunosuppressive medications while retaining kidney function are necessary for improving graft and patient survival in children. This study will evaluate the safety of a regimen containing alemtuzumab after kidney transplantation, followed by steroid avoidance and calcineurin inhibitor withdrawal in pediatric renal transplant recipients 1 to 20 years of age.
The accrual period is scheduled for 18 months. The study follow-up period will last 24 months. All participants enrolled will undergo this treatment schedule: 1.) All participants will receive intravenous alemtuzumab one day before transplantation and 1 day after transplantation. 2.) Mycophenolate mofetil (MMF) will be administered orally no later than 2 days after transplantation. 3.) Participants will begin to take oral tacrolimus twice a day 1 to 3 days after transplantation until Weeks 8 through 12 when 4.) Sirolimus will be initiated. 5.) Sirolimus and MMF will be taken orally until Month 24.
Blood collection will occur at baseline, 1 day before transplant, at Days 1 and 3, at Weeks 2, 4, 6, 8, 10, and at Months 3 through 24. Scheduled kidney (renal) biopsies will be performed at transplant, during Weeks 8 through 12, immediately before conversion to sirolimus, and at Months 6 and 24.
- Being tested
- Alemtuzumab, Tacrolimus, Mycophenolate mofetil, Sirolimus
- Keywords
- End stage renal disease, Kidney transplantation, Renal transplantation, Kidney failure, Pediatric renal transplant recipients, Alemtuzumab, Campath, Mycophenolate mofetil, MMF, CellCept, Tacrolimus, Prograf, Sirolimus, Rapamycin
- Medical subject headings
- Kidney Failure, Chronic, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlemtuzumabDrug
Also called Campath, Campath- 1H
Administered intravenously over a period of 2-3 hours. Two doses total, the first will be one day before transplant and the second will be on the day following transplantation. Pre-medication with methylprednisolone, acetaminophen, and Benadryl will be administered before each dose.
TacrolimusDrug
Also called Prograf
Administered orally at a dose of 0.05-0.1 mg/kg twice daily, beginning 1-3 days following transplantation and continuing until weeks 8-12. Tacrolimus will be discontinued and a treatment regimen with sirolimus will be initiated between weeks 8-12 but some overlap with these medications is possible.
Also called CellCept
Per recommendation
SirolimusDrug
Also called Rapamycin
Administered by either liquid or tablet every 12 hours from month 6 until month 24. Dosage will vary throughout the treatment course.
| Study group | Role | What they receive |
|---|---|---|
| Alemtuzumab (Campath) | Experimental | In this open-label, single-arm trial , participants will be administered a 0.3 mg/kg dose of alemtuzumab (Campath) intravenously one day prior to kidney transplantation and one day post kidney transplantation. Participants will then receive a maintenance immunosuppressive regimen of tacrolimus and mycophenolate mofetil (MMF) for 8 to 12 weeks, followed by sirolimus and MMF until 24 months post transplantation. Receives: Drug: Alemtuzumab; Drug: Tacrolimus; Drug: Mycophenolate mofetil; Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Proportion of Participants With Graft Loss or Death Within 12 Months Post Kidney Transplantation
Graft loss is defined as the need for dialysis for more than 30 days duration, allograft nephrectomy, or the decision to withdraw immunosuppression due to graft failure.
Measured: Up to one year post kidney transplantation procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2005 (estimated)
- Study startJan 2005
- Primary completionNov 2009
- Study completionNov 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Kidney Failure, ChronicStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Cooperative Clinical Trials in Pediatric Transplantation
- Responsible party
- Sponsor
- Investigators
- William Harmon, MD, Study chair, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00240994
- Sponsor's protocol ID
- DAIT PC01
- Status last verified
- Nov 2016
- First submitted
- 14 Oct 2005
- Last updated
- 2 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Participant level data and additional relevant materials are available to the public in the Immunology Database and Analysis Portal (ImmPort). ImmPort is a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
Publications
Wolff G, Strecker K, Vester U, Latta K, Ehrich JH. Non-compliance following renal transplantation in children and adolescents. Pediatr Nephrol. 1998 Nov;12(9):703-8. doi: 10.1007/s004670050531.
PubMed 9874312Ciancio G, Burke GW, Gaynor JJ, Mattiazzi A, Roohipour R, Carreno MR, Roth D, Ruiz P, Kupin W, Rosen A, Esquenazi V, Tzakis AG, Miller J. The use of Campath-1H as induction therapy in renal transplantation: preliminary results. Transplantation. 2004 Aug 15;78(3):426-33. doi: 10.1097/01.tp.0000128625.29654.eb.
PubMed 15316372Rao V, Pirsch JD, Becker BN, Knechtle SJ. Sirolimus monotherapy following Campath-1H induction. Transplant Proc. 2003 May;35(3 Suppl):128S-130S. doi: 10.1016/s0041-1345(03)00227-6.
PubMed 12742484Kreis H, Cisterne JM, Land W, Wramner L, Squifflet JP, Abramowicz D, Campistol JM, Morales JM, Grinyo JM, Mourad G, Berthoux FC, Brattstrom C, Lebranchu Y, Vialtel P. Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients. Transplantation. 2000 Apr 15;69(7):1252-60. doi: 10.1097/00007890-200004150-00009.
PubMed 10798738Watson 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 15888040De Serres SA, Mfarrej BG, Magee CN, Benitez F, Ashoor I, Sayegh MH, Harmon WE, Najafian N. Immune profile of pediatric renal transplant recipients following alemtuzumab induction. J Am Soc Nephrol. 2012 Jan;23(1):174-82. doi: 10.1681/ASN.2011040360. Epub 2011 Nov 3.
PubMed 22052056
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Exploratory Study to Determine the Safety and Study the Immunomodulatory Functions of Induction Therapy With Campath, Combined With Chronic Immunosuppression With Mycophenolate Mofetil and Sirolimus
- ClinicalTrials.gov ID
- NCT00240994
- Acronym / sponsor ID
- DAIT PC01
- Keywords
- End stage renal disease, Kidney transplantation, Renal transplantation, Kidney failure, Pediatric renal transplant recipients, Alemtuzumab, Campath, Mycophenolate mofetil
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Cooperative Clinical Trials in Pediatric Transplantation
- Study start
- Jan 2005
- Primary completion
- Nov 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 18 Oct 2005 (estimated)
- Results
- Posted 25 Oct 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety of alemtuzumab after kidney transplantation as part of a multitherapy regimen to prevent kidney graft loss and death and to avoid steroids and chronic use of calcineurin inhibitors in pediatric renal transplant recipients 1 to 20 years of age.
Detailed description
Kidney transplantation is widely considered to be the treatment of choice for children with End Stage Renal Disease (ESRD). Improvements in surgical techniques, donor selection, and immunosuppression practices, as well as the enhanced experience of specialized pediatric transplant teams, have all led to marked improvements in patient and kidney graft survival in infants and young children ages 1 to 10. However, young children now have more infections following transplant previously. Also, improved graft survival is not observed in pediatric renal transplant recipients 11 to 17 years of age. Some studies do indicate that the poor long term outcome of patient and kidney survival observed in this age group may be caused by noncompliance with immunosuppressive medications. Therefore, protocols that minimize the use of immunosuppressive medications while retaining kidney function are necessary for improving graft and patient survival in children. This study will evaluate the safety of a regimen containing alemtuzumab after kidney transplantation, followed by steroid avoidance and calcineurin inhibitor withdrawal in pediatric renal transplant recipients 1 to 20 years of age.
The accrual period is scheduled for 18 months. The study follow-up period will last 24 months. All participants enrolled will undergo this treatment schedule: 1.) All participants will receive intravenous alemtuzumab one day before transplantation and 1 day after transplantation. 2.) Mycophenolate mofetil (MMF) will be administered orally no later than 2 days after transplantation. 3.) Participants will begin to take oral tacrolimus twice a day 1 to 3 days after transplantation until Weeks 8 through 12 when 4.) Sirolimus will be initiated. 5.) Sirolimus and MMF will be taken orally until Month 24.
Blood collection will occur at baseline, 1 day before transplant, at Days 1 and 3, at Weeks 2, 4, 6, 8, 10, and at Months 3 through 24. Scheduled kidney (renal) biopsies will be performed at transplant, during Weeks 8 through 12, immediately before conversion to sirolimus, and at Months 6 and 24.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Alemtuzumab (Campath) | Experimental | Drug: Alemtuzumab, Drug: Tacrolimus, Drug: Mycophenolate mofetil, Drug: SirolimusIn this open-label, single-arm trial , participants will be administered a 0.3 mg/kg dose of alemtuzumab (Campath) intravenously one day prior to kidney transplantation and one day post kidney transplantation. Participants will then receive a maintenance immunosuppressive regimen of tacrolimus and mycophenolate mofetil (MMF) for 8 to 12 weeks, followed by sirolimus and MMF until 24 months post transplantation. |
Who may qualify
- Ages
- 1 year to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- Between the ages of 1 to 20 (prior to 21st birthday)
- End Stage Renal Disease
- Necessity of kidney transplant
- First kidney transplant received from a living donor
- A living kidney donor identified
Key exclusion criteria (14 listed)
- Recipient of a deceased donor kidney transplant
- Multiorgan transplant
- History of prior organ transplantation
- Participant sensitized to greater than 0% Panel Reactive Antibody (PRA) within 4 weeks before study enrollment. (If participant receives a blood transfusion status post PRA test, then the PRA must be repeated within 1 week of transplantation)
- Participants with human leukocyte antigen (HLA) identical living related donors
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlemtuzumabAlso: Campath, Campath- 1HAdministered intravenously over a period of 2-3 hours. Two doses total, the first will be one day before transplant and the second will be on the day following transplantation. Pre-medication with methylprednisolone, acetaminophen, and Benadryl will be administered before each dose. | Drug | Alemtuzumab (Campath) |
| TacrolimusAlso: PrografAdministered orally at a dose of 0.05-0.1 mg/kg twice daily, beginning 1-3 days following transplantation and continuing until weeks 8-12. Tacrolimus will be discontinued and a treatment regimen with sirolimus will be initiated between weeks 8-12 but some overlap with these medications is possible. | Drug | Alemtuzumab (Campath) |
| Mycophenolate mofetilAlso: CellCeptPer recommendation | Drug | Alemtuzumab (Campath) |
| SirolimusAlso: RapamycinAdministered by either liquid or tablet every 12 hours from month 6 until month 24. Dosage will vary throughout the treatment course. | Drug | Alemtuzumab (Campath) |
Primary outcome
The Proportion of Participants With Graft Loss or Death Within 12 Months Post Kidney Transplantation
Time frame: Up to one year post kidney transplantation procedure
Graft loss is defined as the need for dialysis for more than 30 days duration, allograft nephrectomy, or the decision to withdraw immunosuppression due to graft failure.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 9874312Wolff G, Strecker K, Vester U, Latta K, Ehrich JH. Non-compliance following renal transplantation in children and adolescents. Pediatr Nephrol. 1998 Nov;12(9):703-8. doi: 10.1007/s004670050531.
- Background: PubMed 15316372Ciancio G, Burke GW, Gaynor JJ, Mattiazzi A, Roohipour R, Carreno MR, Roth D, Ruiz P, Kupin W, Rosen A, Esquenazi V, Tzakis AG, Miller J. The use of Campath-1H as induction therapy in renal transplantation: preliminary results. Transplantation. 2004 Aug 15;78(3):426-33. doi: 10.1097/01.tp.0000128625.29654.eb.
- Background: PubMed 12742484Rao V, Pirsch JD, Becker BN, Knechtle SJ. Sirolimus monotherapy following Campath-1H induction. Transplant Proc. 2003 May;35(3 Suppl):128S-130S. doi: 10.1016/s0041-1345(03)00227-6.
- Background: PubMed 10798738Kreis H, Cisterne JM, Land W, Wramner L, Squifflet JP, Abramowicz D, Campistol JM, Morales JM, Grinyo JM, Mourad G, Berthoux FC, Brattstrom C, Lebranchu Y, Vialtel P. Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients. Transplantation. 2000 Apr 15;69(7):1252-60. doi: 10.1097/00007890-200004150-00009.
- Background: PubMed 15888040Watson 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.
- Results publication: PubMed 22052056De Serres SA, Mfarrej BG, Magee CN, Benitez F, Ashoor I, Sayegh MH, Harmon WE, Najafian N. Immune profile of pediatric renal transplant recipients following alemtuzumab induction. J Am Soc Nephrol. 2012 Jan;23(1):174-82. doi: 10.1681/ASN.2011040360. Epub 2011 Nov 3.
- National Institute of Allergy and Infectious Diseases (NIAID)Link provided by the sponsor.
- Division of Allergy, Immunology, and Transplantation (DAIT)Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Participant level data and additional relevant materials are available to the public in the Immunology Database and Analysis Portal (ImmPort). ImmPort is a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William Harmon, MD study chair
Boston Children's Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alemtuzumab, Tacrolimus and Mycophenolate mofetil in people with Kidney Failure, Chronic and Kidney Transplantation, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 sites 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 10 inclusion and 14 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 2 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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 phase mean?
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 25 Oct 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?
The Proportion of Participants With Graft Loss or Death Within 12 Months Post Kidney Transplantation (time frame: Up to one year post kidney transplantation procedure). 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 NCT00240994, which also lists 6 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 2 Jan 2017.