Kidney TransplantationPhase 2NCT00801632
Combined Kidney and Bone Marrow Transplantation to Prevent Kidney Transplant Rejection
A Phase 2 study testing Kidney Transplantation, Bone marrow transplantation and MEDI-507 in people with Kidney Transplantation and Kidney Failure, Chronic, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
In small initial studies, combined kidney and bone marrow transplants from the same donor have permitted some individuals to stop taking anti-rejection medicines without rejecting their transplant. This clinical trial will study this method in a greater number of people to determine if it is indeed effective and safe. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Kidney Transplantation, Kidney Failure, Chronic
- What is being tested?
- Kidney Transplantation, Bone marrow transplantation and MEDI-507
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2008to Nov 2014
- 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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Awaiting first or second transplant with a living donor or first transplant with a cadaveric donor
- For living-donor transplants, must have one or more HLA antigen-mismatched donors identified
- Serologic evidence of prior exposure to Epstein-Barr virus (EBV)
Who cannot join
- ABO blood group-incompatibility for a kidney graft of tissue from a donor
- Decreased circulating white blood cell count
- Positive for HIV-1, hepatitis B and C viruses
- Have had prior radiation therapy that could limit dose
- Lung capacity <50% of predicted normal
- Evidence of insufficient cardiac capacity
Show all 9Show fewer
- Unwilling to use adequate contraception until 2 years after transplant
- Lactation or pregnancy
- Presence of antibody against the donor
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: Renal Allograft Tolerance Through Mixed Chimerism
In small initial studies, combined kidney and bone marrow transplants from the same donor have permitted some individuals to stop taking anti-rejection medicines without rejecting their transplant. This clinical trial will study this method in a greater number of people to determine if it is indeed effective and safe.
Read the detailed description
All patients receiving an organ or tissue transplant must take special medicines known as "immunosuppressive drugs" in order to prevent the immune system from rejecting the transplant. These drugs can be very effective, but they leave the patient at an increased risk of serious infections and certain types of cancer. New methods of preventing transplant rejection are needed.
Researchers have found that transplanting both bone marrow and a kidney from the same donor can create what is called "mixed chimerism." This means that the transplant recipient has a mixture of the donor and recipient's immune systems. It is believed that this mixture of immune cells can prevent rejection of the kidney. In a small prior study, performing a kidney transplant together with a bone marrow transplant from the same donor allowed 4 of 5 patients to stop taking immunosuppressive drugs altogether, without rejecting their transplant. This clinical trial will study more patients to confirm if the technique is safe and effective.
Patients eligible for this study must be candidates for a living kidney transplant, and have an eligible donor identified. The transplant recipient and donor must both consent to participate in this study. Transplant recipients enrolled in the study will receive both kidney and bone marrow transplants from the same living donor. Prior to the transplant procedure, the transplant recipient will undergo a "conditioning regimen" that prepares their immune system for the recipient's immune (bone marrow) cells. This conditioning regimen is a combination of chemotherapy, radiation, immunosuppressive drugs and specialized medications called rituximab and MEDI-507. MEDI-507 is an investigational medication that has not been approved by the FDA. After the transplant procedure, transplant recipients will be prescribed steroids for several weeks and immunosuppressive drugs. After 2 months, the dose of the immunosuppressive drugs will slowly be decreased to zero in patients whose immune system and kidney function meet certain criteria.
Transplant recipients enrolled into the study will be hospitalized for 1 week prior to the transplant procedure. After the transplant, patients will remain in the hospital until the doctor feels they are well enough to go home. Recipients will receive approximately monthly checkups over a period of 2 years after transplant, plus a checkup at 2 ½, 3, 3 ½ , 4, and 5 years after transplant. Checkups will include physical exams, and blood and urine tests to assess immune system and kidney function. At four of these checkups, a kidney biopsy will be requested.
Transplant donors enrolled in the study will attend a screening visit, which will include a physical exam, blood tests and chest x-ray. Eligible donors will be admitted to the hospital for 3-5 days, where bone marrow will be collected prior to removal of the kidney. Transplant donors may be asked at a later date to donate additional blood samples for research purposes.
- Conditions
- Kidney Transplantation, Kidney Failure, Chronic
- Being tested
- Kidney Transplantation, Bone marrow transplantation, MEDI-507, cyclophosphamide, rituximab
- Keywords
- renal allograft tolerance, mixed chimerism, kidney transplant, bone marrow transplant, antirejection, immunosuppression
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Kidney TransplantationProcedure or surgery
Also called Renal Transplantation
Surgical transplantation of donor kidney
Bone marrow transplantationProcedure or surgery
During kidney transplant, bone marrow cells donated by the same donor as the kidney are given through a plastic tube placed in a vein in the chest, underneath the collarbone
MEDI-507Biological
Also called siplizumab, anti-CD2 monoclonal antibody
0.1 mg/kg on day -2; 0.6 mg/kg on days -1,0,1
cyclophosphamideDrug
Also called Cytoxan
60 mg/kg infusion on days -5, -4
rituximabBiological
Also called Rituxan
375 mg/m^2 infusion on days -7, -2, 5, and 12
TacrolimusDrug
Also called PROGRAF®
0.05 mg/kg intravenously twice daily starting on day -1, adjusted to trough level of 10-15ng/ml, then tapered (if eligible) on days 1, 7, 14, 21, 28, 42, and 56
corticosteroidsDrug
Also called methylprednisolone, prednisone
2 mg/kg prednisone on day 4, with an additional 500-mg pulse of methylprednisolone given on days 10, 11, and 12, and then tapered off by day 20
thymic irradiationRadiation
700 cGy of thymic irradiation administered in a single dose on day -1
| Study group | Role | What they receive |
|---|---|---|
| Kidney and Marrow Recipients | Experimental | Combined kidney and bone marrow transplant Receives: Procedure: Kidney Transplantation; Procedure: Bone marrow transplantation; Biological: MEDI-507; Drug: cyclophosphamide; Biological: rituximab; Drug: Tacrolimus; Drug: corticosteroids; Radiation: thymic irradiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Successfully Withdrawn Off of Immunosuppressant Medication for 104 Weeks
A participant was considered a success if they were off immunosuppressive therapy for 104 consecutive weeks leading up to study week 208 (48 months post-transplant) or study termination, whichever occurred first.
Measured: 48 months post-transplant
Secondary outcomes (7)
Percentage of Participants Experiencing Acute Rejection
The percentage of participants who experience an acute rejection. Acute rejection is defined as a biopsy with findings of Banff score of grade IA or higher. The Banff classification is as follows: grade IA is >25% of parenchyma affected and foci of moderate tubulitis; Grade IB is >25% of parenchyma affected and foci of severe tubulitis; Grade IIA is mild to moderate intimal arteritis; Grade IIB is severe intimal arteritis comprising >25% of the luminal area; Grade III is "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation.
Measured: Transplantation until study completion or participant termination (up to five years)
Change in Renal Function
Change in renal function as seen in serum creatinine values from baseline until study completion or participant termination. Baseline is defined as the lowest serum creatinine collected during stabilization period or in the four weeks following the end of the stabilization period. The stabilization period is defined as four consecutive creatinine values close in value (not differing more than 0.3 mg/dL). Higher results indicate poorer kidney function, as creatinine is removed from the body by the kidneys.
Measured: Transplantation until study completion or participant termination (up to five years)
Percentage of Participants With Graft Survival Through 156 Weeks
The percentage of participants with graft survival from transplantation through 156 weeks. Participants who terminated from the study prior to Week 156 without meeting the event were excluded. Graft survival is defined as the time to week 156 or graft loss. Graft loss is defined as the day on which a graft is deemed irreversibly nonfunctional and dialysis is begun, a transplantectomy is performed, or the participant is re-transplanted, whichever comes first. Six consecutive weeks of dialysis are required for the diagnosis of graft loss, though the date of graft loss will be defined as the date of first dialysis.
Measured: Transplantation until week 156
Percentage of Participants Surviving Through 156 Weeks
The percentage of participants who survived from transplantation through 156 weeks. Participants who terminated from the study prior to Week 156 without meeting the event were excluded.
Measured: Transplantation until week 156
Time to Neutrophil Recovery Following Transplant
Time (in days) until neutrophil recovery following transplant. Neutrophil recovery is defined as an absolute neutrophil count (ANC) > 500/mm^3 at three consecutive assessments on different days post-transplant. Time to recovery is time from transplantation until the first assessment date used to confirm the recovery.
Measured: Transplantation until study completion or participant termination (participants followed up to five years)
Time to Platelet Recovery Following Transplant
Time (in days) until platelet recovery following transplant. Platelet recovery is defined as a platelet count >20,000 /mm^3 and where no transfusion is required. Time to recovery is time from transplantation until platelet value recovers.
Measured: Transplantation until study completion or participant termination (participants followed up to five years)
Percentage of Participants Experiencing a Clinically Significant Invasive or Resistant Opportunistic Infection
Clinically significant invasive or resistant opportunistic infections include cytomegalovirus, herpes zoster, and candida.
Measured: Transplantation until study completion or participant termination (participants followed up to five years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2008 (estimated)
- Study startDec 2008
- Primary completionApr 2014
- Study completionNov 2014
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 (2)Papers the sponsor has linked to this study.
- Other trials for Kidney TransplantationStudies 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Immune Tolerance Network (ITN)
- Responsible party
- Sponsor
- Investigators
- David Sachs, MD, Principal investigator, Massacusetts General HospitalBen Cosimi, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00801632
- Sponsor's protocol ID
- DAIT ITN036ST
- Status last verified
- Nov 2015
- First submitted
- 2 Dec 2008
- Last updated
- 10 Nov 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Kawai T, Cosimi AB, Spitzer TR, Tolkoff-Rubin N, Suthanthiran M, Saidman SL, Shaffer J, Preffer FI, Ding R, Sharma V, Fishman JA, Dey B, Ko DS, Hertl M, Goes NB, Wong W, Williams WW Jr, Colvin RB, Sykes M, Sachs DH. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2008 Jan 24;358(4):353-61. doi: 10.1056/NEJMoa071074.
PubMed 18216355Kawai T, Sachs DH, Sykes M, Cosimi AB; Immune Tolerance Network. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2013 May 9;368(19):1850-2. doi: 10.1056/NEJMc1213779. No abstract available.
PubMed 23656665
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Renal Allograft Tolerance Through Mixed Chimerism
- ClinicalTrials.gov ID
- NCT00801632
- Acronym / sponsor ID
- DAIT ITN036ST
- Conditions
- Kidney Transplantation, Kidney Failure, Chronic
- Keywords
- renal allograft tolerance, mixed chimerism, kidney transplant, bone marrow transplant, antirejection, immunosuppression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Immune Tolerance Network (ITN)
- Study start
- Dec 2008
- Primary completion
- Apr 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 3 Dec 2008 (estimated)
- Results
- Posted 12 May 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In small initial studies, combined kidney and bone marrow transplants from the same donor have permitted some individuals to stop taking anti-rejection medicines without rejecting their transplant. This clinical trial will study this method in a greater number of people to determine if it is indeed effective and safe.
Detailed description
All patients receiving an organ or tissue transplant must take special medicines known as "immunosuppressive drugs" in order to prevent the immune system from rejecting the transplant. These drugs can be very effective, but they leave the patient at an increased risk of serious infections and certain types of cancer. New methods of preventing transplant rejection are needed.
Researchers have found that transplanting both bone marrow and a kidney from the same donor can create what is called "mixed chimerism." This means that the transplant recipient has a mixture of the donor and recipient's immune systems. It is believed that this mixture of immune cells can prevent rejection of the kidney. In a small prior study, performing a kidney transplant together with a bone marrow transplant from the same donor allowed 4 of 5 patients to stop taking immunosuppressive drugs altogether, without rejecting their transplant. This clinical trial will study more patients to confirm if the technique is safe and effective.
Patients eligible for this study must be candidates for a living kidney transplant, and have an eligible donor identified. The transplant recipient and donor must both consent to participate in this study. Transplant recipients enrolled in the study will receive both kidney and bone marrow transplants from the same living donor. Prior to the transplant procedure, the transplant recipient will undergo a "conditioning regimen" that prepares their immune system for the recipient's immune (bone marrow) cells. This conditioning regimen is a combination of chemotherapy, radiation, immunosuppressive drugs and specialized medications called rituximab and MEDI-507. MEDI-507 is an investigational medication that has not been approved by the FDA. After the transplant procedure, transplant recipients will be prescribed steroids for several weeks and immunosuppressive drugs. After 2 months, the dose of the immunosuppressive drugs will slowly be decreased to zero in patients whose immune system and kidney function meet certain criteria.
Transplant recipients enrolled into the study will be hospitalized for 1 week prior to the transplant procedure. After the transplant, patients will remain in the hospital until the doctor feels they are well enough to go home. Recipients will receive approximately monthly checkups over a period of 2 years after transplant, plus a checkup at 2 ½, 3, 3 ½ , 4, and 5 years after transplant. Checkups will include physical exams, and blood and urine tests to assess immune system and kidney function. At four of these checkups, a kidney biopsy will be requested.
Transplant donors enrolled in the study will attend a screening visit, which will include a physical exam, blood tests and chest x-ray. Eligible donors will be admitted to the hospital for 3-5 days, where bone marrow will be collected prior to removal of the kidney. Transplant donors may be asked at a later date to donate additional blood samples for research purposes.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Kidney and Marrow Recipients | Experimental | Procedure: Kidney Transplantation, Procedure: Bone marrow transplantation, Biological: MEDI-507, Drug: cyclophosphamide, Biological: rituximab, Drug: Tacrolimus, Drug: corticosteroids, Radiation: thymic irradiationCombined kidney and bone marrow transplant |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Awaiting first or second transplant with a living donor or first transplant with a cadaveric donor
- For living-donor transplants, must have one or more HLA antigen-mismatched donors identified
- Serologic evidence of prior exposure to Epstein-Barr virus (EBV)
Key exclusion criteria (9 listed)
- ABO blood group-incompatibility for a kidney graft of tissue from a donor
- Decreased circulating white blood cell count
- Positive for HIV-1, hepatitis B and C viruses
- Have had prior radiation therapy that could limit dose
- Lung capacity <50% of predicted normal
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 |
|---|---|---|
| Kidney TransplantationAlso: Renal TransplantationSurgical transplantation of donor kidney | Procedure or surgery | Kidney and Marrow Recipients |
| Bone marrow transplantationDuring kidney transplant, bone marrow cells donated by the same donor as the kidney are given through a plastic tube placed in a vein in the chest, underneath the collarbone | Procedure or surgery | Kidney and Marrow Recipients |
| MEDI-507Also: siplizumab, anti-CD2 monoclonal antibody0.1 mg/kg on day -2; 0.6 mg/kg on days -1,0,1 | Biological | Kidney and Marrow Recipients |
| cyclophosphamideAlso: Cytoxan60 mg/kg infusion on days -5, -4 | Drug | Kidney and Marrow Recipients |
| rituximabAlso: Rituxan375 mg/m^2 infusion on days -7, -2, 5, and 12 | Biological | Kidney and Marrow Recipients |
| TacrolimusAlso: PROGRAF®0.05 mg/kg intravenously twice daily starting on day -1, adjusted to trough level of 10-15ng/ml, then tapered (if eligible) on days 1, 7, 14, 21, 28, 42, and 56 | Drug | Kidney and Marrow Recipients |
| corticosteroidsAlso: methylprednisolone, prednisone2 mg/kg prednisone on day 4, with an additional 500-mg pulse of methylprednisolone given on days 10, 11, and 12, and then tapered off by day 20 | Drug | Kidney and Marrow Recipients |
| thymic irradiation700 cGy of thymic irradiation administered in a single dose on day -1 | Radiation | Kidney and Marrow Recipients |
Primary outcome
Number of Participants Successfully Withdrawn Off of Immunosuppressant Medication for 104 Weeks
Time frame: 48 months post-transplant
A participant was considered a success if they were off immunosuppressive therapy for 104 consecutive weeks leading up to study week 208 (48 months post-transplant) or study termination, whichever occurred first.
7 secondary outcomes
Percentage of Participants Experiencing Acute Rejection
Time frame: Transplantation until study completion or participant termination (up to five years)
Change in Renal Function
Time frame: Transplantation until study completion or participant termination (up to five years)
Percentage of Participants With Graft Survival Through 156 Weeks
Time frame: Transplantation until week 156
Percentage of Participants Surviving Through 156 Weeks
Time frame: Transplantation until week 156
Time to Neutrophil Recovery Following Transplant
Time frame: Transplantation until study completion or participant termination (participants followed up to five years)
Time to Platelet Recovery Following Transplant
Time frame: Transplantation until study completion or participant termination (participants followed up to five years)
Percentage of Participants Experiencing a Clinically Significant Invasive or Resistant Opportunistic Infection
Time frame: Transplantation until study completion or participant termination (participants followed up to five years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18216355Kawai T, Cosimi AB, Spitzer TR, Tolkoff-Rubin N, Suthanthiran M, Saidman SL, Shaffer J, Preffer FI, Ding R, Sharma V, Fishman JA, Dey B, Ko DS, Hertl M, Goes NB, Wong W, Williams WW Jr, Colvin RB, Sykes M, Sachs DH. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2008 Jan 24;358(4):353-61. doi: 10.1056/NEJMoa071074.
- Results publication: PubMed 23656665Kawai T, Sachs DH, Sykes M, Cosimi AB; Immune Tolerance Network. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2013 May 9;368(19):1850-2. doi: 10.1056/NEJMc1213779. No abstract available.
- Immune Tolerance NetworkLink provided by the sponsor.
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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.
David Sachs, MD principal investigator
Massacusetts General Hospital
Ben Cosimi, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Kidney Transplantation, Bone marrow transplantation and MEDI-507 in people with Kidney Transplantation and Kidney Failure, Chronic, run by National Institute of Allergy and Infectious Diseases (NIAID) 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 3 inclusion and 9 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 10 Nov 2015. 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 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 12 May 2015). 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 Participants Successfully Withdrawn Off of Immunosuppressant Medication for 104 Weeks (time frame: 48 months 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 NCT00801632, which also lists 2 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 10 Nov 2015.