End-stage Renal DiseasePhase 1NCT00063817
Reducing the Risk of Transplant Rejection: Simultaneous Kidney and Bone Marrow Transplant
A Phase 1 study testing Conditioning Regimen in people with End-stage Renal Disease and Renal Transplantation, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This study will examine the safety and effectiveness of a combination kidney and bone marrow transplant from a relative with the same (or nearly the same) blood cell type as the transplant recipient. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- End-stage Renal Disease, Renal Transplantation, Kidney Transplantation
- What is being tested?
- Conditioning Regimen
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2003to Jul 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- End-stage renal disease (ESRD) without prior sensitization (defined as Panel Reactive Antibody [PRA] greater than 20%) within the 60 days prior to transplant as measured by cytotoxicity assays, ELISA, and flow cytometry;
- Undergoing a first or second transplant;
- Receiving a transplant from a living related donor who is ABO (blood type) compatible and haploidentical (3, 4, or 5 antigen match by serologic typing);
- Cardiac ejection fraction greater than 40%;
- Forced expiratory volume (FEV1) greater than 50%;
- Liver function tests, bilirubin, and coagulation studies less than 2 X normal;
- White blood cells greater than 2000/mm^3; abd
- Platelets greater than 100,000/mm^3
Who cannot join
- Positive donor lymphocyte cross-match;
- HIV-1 infected;
- Positive hepatitis B surface antigen (HbsAg);
- Hepatitis C virus infected;
- History of cancer;
- Prior dose-limiting radiation therapy;
Show all 9Show fewer
- Pregnant, breastfeeding, or planning pregnancy within the time frame of the study;
- Enrolled in another investigational drug study within 30 days prior to study entry; or
- Receiving maintenance immunosuppression within 3 months before the conditioning regimen begins
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 (ITN010ST)
This study will examine the safety and effectiveness of a combination kidney and bone marrow transplant from a relative with the same (or nearly the same) blood cell type as the transplant recipient. An investigational medication will be given prior to and after the transplant to help protect the transplanted kidney from attack by the body's immune system.
Read the detailed description
Of the two currently available treatments for kidney failure, long-term dialysis and kidney transplantation, only kidney transplantation provides a potential cure. After a kidney transplant, the body's immune system recognizes the kidney as foreign and tries to attack and destroy it in a process called rejection. To avoid rejection, participants must take medications called immunosuppressants or anti-rejection drugs. It is believed that by transplanting bone marrow at the same time as a solid organ such as a kidney, a state of "mixed chimerism" (a mixing of the donor and recipient's immune system) can be achieved. Mixed chimerism may prevent rejection without the need for anti-rejection drugs.
Participants in this study will receive a simultaneous bone marrow and kidney transplant from the same living related donor in an attempt to establish mixed chimerism. Prior to transplantation, participants will undergo a "conditioning regimen" involving cyclophosphamide chemotherapy, radiation to the thymus gland, and four immunosuppressive medications: cyclosporine A, a man-made antibody known as rituximab to suppress B cells, a short course of steroids, and a T-cell depleting antibody known as MEDI-507. MEDI-507 is an investigational medication that has not been approved by the FDA. The primary goal of the study is to investigate the safety of the conditioning regimen and its ability to promote mixed chimerism so that the transplanted kidney is not destroyed. The study will also determine whether participants with mixed chimerism can eventually be safely removed from long-term immunosuppressive therapy following transplantation.
Participants will be assessed before and after transplantation and will be followed ≤36 months.
- Being tested
- Conditioning Regimen
- Keywords
- End-stage renal disease, Renal Transplant, Bone Marrow Transplant, nonmyeloablative conditioning regimen
- 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.
Conditioning RegimenDrug
Also called nonmyeloablative preparative regimen
Cyclophosphamide 60 mg per kilogram (kg) of body weight per day intravenously (IV) on days -5 and -4 with respect to transplantation; humanized anti-CD2 monoclonal antibody (MEDI-507) 0.6 mg per kg on days -1, 0, and 1 (after test dose of 0.1 mg per kg on day -2); and cyclosporine A 5 mg per kg IV and thymic irradiation (700 cGy) on day -1. Hemodialysis was performed before and 14 hours after each dose of cyclophosphamide.Kidney transplantation was followed by IV infusion of donor bone marrow. Oral cyclosporine A was administered postoperatively, 8 to 12 mg per kg per day, with target trough blood levels of 250 to 350 ng per milliliter; the dose was tapered and discontinued over a period of several months. Protocol amendment that applied to participant 4 and 5: rituximab, 375 mg per square meter of body-surface area days -7 and -2; and prednisone, 2 mg per kg per day starting on the day of transplantation with tapering over the next 10 days.
| Study group | Role | What they receive |
|---|---|---|
| Conditioning Regimen | Experimental | Cyclophosphamide intravenously (IV) on days -5 and -4 with respect to transplantation; MEDI-507 on days -1, 0, and 1 (after a test dose of 0.1 mg per kg on day -2); and cyclosporine A IV and thymic irradiation on day -1. Hemodialysis was performed before and 14 hours after each dose of cyclophosphamide.Kidney transplantation was followed by IV infusion of donor bone marrow. Oral cyclosporine A was administered daily postoperatively, with target trough blood levels of 250 to 350 ng per milliliter; the dose was tapered and discontinued over a period of several months.
Amendment applicable to the 4th and 5th participant: rituximab on days -7 and -2; and prednisone, 2 mg per kg per day starting on the day of transplantation with tapering over the next 10 days. Receives: Drug: Conditioning Regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Graft Survival Twenty-Four Months Post Transplantation
Defined by kidney transplant survival at month 24 post transplantation with successful withdrawal of cyclosporine following transplantation, in the absence of maintenance immunosuppression.
Measured: 24 months (2 Years) Post Transplantation
Secondary outcomes (5)
Participant Survival
During the three-year post-transplant follow-up period for enrolled participants.
Measured: Up to thirty-six months (3 Years) Post Transplantation
Graft Survival
During the three-year post-transplant follow-up period for enrolled participants.
Measured: Up to thirty-six months (3 Years) Post Transplantation
Change from Baseline in Renal Function Using Serum Creatinine
Changes in serum creatinine levels from baseline through post transplantation follow-up period.
Measured: Up to thirty-six months (3 Years) Post Transplantation
Number of Episodes of Acute or Chronic Graft Versus Host Disease (GVHD)
Evaluations for suspected GVHD, including biopsies as appropriate, during routine and/or for cause assessments.
Measured: From Week 1 through thirty-six months (3 Years) Post Transplantation
Number of Adverse Events
As defined by protocol.
Measured: Participant enrollment through <=thirty-six months (3 Years) Post Transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2003 (estimated)
- Study startJun 2003
- Primary completionJan 2009
- Study completionJul 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for End-stage Renal DiseaseStudies 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 1
- 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 H. Sachs, MD, Principal investigator, Department of Medicine, Massachusetts General HospitalA. Benedict Cosimi, MD, Principal investigator, Department of Medicine, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00063817
- Sponsor's protocol ID
- DAIT ITN010ST
- Other IDs
- DAIT NKD03
- Status last verified
- Dec 2017
- First submitted
- 7 Jul 2003
- Last updated
- 27 Dec 2017
- Results posted
- No
- 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 18216355
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Renal Allograft Tolerance Through Mixed Chimerism (ITN010ST)
- ClinicalTrials.gov ID
- NCT00063817
- Acronym / sponsor ID
- DAIT ITN010ST
- Keywords
- End-stage renal disease, Renal Transplant, Bone Marrow Transplant, nonmyeloablative conditioning regimen
- Phase
- Phase 1
- 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
- Jun 2003
- Primary completion
- Jan 2009 (actual)
- Study completion
- Jul 2009 (actual)
- First posted
- 8 Jul 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will examine the safety and effectiveness of a combination kidney and bone marrow transplant from a relative with the same (or nearly the same) blood cell type as the transplant recipient. An investigational medication will be given prior to and after the transplant to help protect the transplanted kidney from attack by the body's immune system.
Detailed description
Of the two currently available treatments for kidney failure, long-term dialysis and kidney transplantation, only kidney transplantation provides a potential cure. After a kidney transplant, the body's immune system recognizes the kidney as foreign and tries to attack and destroy it in a process called rejection. To avoid rejection, participants must take medications called immunosuppressants or anti-rejection drugs. It is believed that by transplanting bone marrow at the same time as a solid organ such as a kidney, a state of "mixed chimerism" (a mixing of the donor and recipient's immune system) can be achieved. Mixed chimerism may prevent rejection without the need for anti-rejection drugs.
Participants in this study will receive a simultaneous bone marrow and kidney transplant from the same living related donor in an attempt to establish mixed chimerism. Prior to transplantation, participants will undergo a "conditioning regimen" involving cyclophosphamide chemotherapy, radiation to the thymus gland, and four immunosuppressive medications: cyclosporine A, a man-made antibody known as rituximab to suppress B cells, a short course of steroids, and a T-cell depleting antibody known as MEDI-507. MEDI-507 is an investigational medication that has not been approved by the FDA. The primary goal of the study is to investigate the safety of the conditioning regimen and its ability to promote mixed chimerism so that the transplanted kidney is not destroyed. The study will also determine whether participants with mixed chimerism can eventually be safely removed from long-term immunosuppressive therapy following transplantation.
Participants will be assessed before and after transplantation and will be followed ≤36 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Conditioning Regimen | Experimental | Drug: Conditioning RegimenCyclophosphamide intravenously (IV) on days -5 and -4 with respect to transplantation; MEDI-507 on days -1, 0, and 1 (after a test dose of 0.1 mg per kg on day -2); and cyclosporine A IV and thymic irradiation on day -1. Hemodialysis was performed before and 14 hours after each dose of cyclophosphamide.Kidney transplantation was followed by IV infusion of donor bone marrow. Oral cyclosporine A was administered daily postoperatively, with target trough blood levels of 250 to 350 ng per milliliter; the dose was tapered and discontinued over a period of several months. Amendment applicable to the 4th and 5th participant: rituximab on days -7 and -2; and prednisone, 2 mg per kg per day starting on the day of transplantation with tapering over the next 10 days. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- End-stage renal disease (ESRD) without prior sensitization (defined as Panel Reactive Antibody [PRA] greater than 20%) within the 60 days prior to transplant as measured by cytotoxicity assays, ELISA, and flow cytometry;
- Undergoing a first or second transplant;
- Receiving a transplant from a living related donor who is ABO (blood type) compatible and haploidentical (3, 4, or 5 antigen match by serologic typing);
- Cardiac ejection fraction greater than 40%;
- Forced expiratory volume (FEV1) greater than 50%;
Key exclusion criteria (9 listed)
- Positive donor lymphocyte cross-match;
- HIV-1 infected;
- Positive hepatitis B surface antigen (HbsAg);
- Hepatitis C virus infected;
- History of cancer;
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 |
|---|---|---|
| Conditioning RegimenAlso: nonmyeloablative preparative regimenCyclophosphamide 60 mg per kilogram (kg) of body weight per day intravenously (IV) on days -5 and -4 with respect to transplantation; humanized anti-CD2 monoclonal antibody (MEDI-507) 0.6 mg per kg on days -1, 0, and 1 (after test dose of 0.1 mg per kg on day -2); and cyclosporine A 5 mg per kg IV and thymic irradiation (700 cGy) on day -1. Hemodialysis was performed before and 14 hours after each dose of cyclophosphamide.Kidney transplantation was followed by IV infusion of donor bone marrow. Oral cyclosporine A was administered postoperatively, 8 to 12 mg per kg per day, with target trough blood levels of 250 to 350 ng per milliliter; the dose was tapered and discontinued over a period of several months. Protocol amendment that applied to participant 4 and 5: rituximab, 375 mg per square meter of body-surface area days -7 and -2; and prednisone, 2 mg per kg per day starting on the day of transplantation with tapering over the next 10 days. | Drug | Conditioning Regimen |
Primary outcome
Graft Survival Twenty-Four Months Post Transplantation
Time frame: 24 months (2 Years) Post Transplantation
Defined by kidney transplant survival at month 24 post transplantation with successful withdrawal of cyclosporine following transplantation, in the absence of maintenance immunosuppression.
5 secondary outcomes
Participant Survival
Time frame: Up to thirty-six months (3 Years) Post Transplantation
Graft Survival
Time frame: Up to thirty-six months (3 Years) Post Transplantation
Change from Baseline in Renal Function Using Serum Creatinine
Time frame: Up to thirty-six months (3 Years) Post Transplantation
Number of Episodes of Acute or Chronic Graft Versus Host Disease (GVHD)
Time frame: From Week 1 through thirty-six months (3 Years) Post Transplantation
Number of Adverse Events
Time frame: Participant enrollment through <=thirty-six months (3 Years) Post Transplantation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2017.
- Results publication: 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.
- National Institute of Allergy and Infectious Diseases websiteLink provided by the sponsor.
- Click here for the Immune Tolerance Network websiteLink 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 H. Sachs, MD principal investigator
Department of Medicine, Massachusetts General Hospital
A. Benedict Cosimi, MD principal investigator
Department of Medicine, 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 1 study testing Conditioning Regimen in people with End-stage Renal Disease and Renal Transplantation, 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 8 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 27 Dec 2017. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Graft Survival Twenty-Four Months Post Transplantation (time frame: 24 months (2 Years) Post Transplantation). 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 NCT00063817, which also lists 1 linked publication.
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 27 Dec 2017.