Renal FailurePhase 1NCT04540380
Renal Allograft Tolerance Through Mixed Chimerism - SMC/MGH
A Phase 1 study testing Rituximab, Fludarabine, Cyclophosphamide, Thymic irradiation and Siplizumab and Combined bone marrow and kidney transplant in people with Renal Failure, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
The goal is to investigate the safety of the conditioning regimen, and its ability to induce donor/recipient lymphohematopoietic chimerism without Chimerism Transition Syndrome (CTS), which may result in donor-specific unresponsiveness (tolerance) to the renal allograft in the absence of maintenance immunosuppression. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Renal Failure
- What is being tested?
- Rituximab, Fludarabine, Cyclophosphamide, Thymic irradiation and Siplizumab and Combined bone marrow and kidney transplant
- Type of treatment
- Surgery or procedure
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2021to Jun 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- Male or female 18-65 years of age.
- Candidate for a living-donor renal allograft from an HLA mismatched donor
- Subjects with chronic kidney disease stage or ESRD who are treated with either hemodialysis or peritoneal dialysis.
- First transplant.
- Use of FDA-approved methods of contraception
- Ability to understand and provide informed consent.
- Negative COVID at screening and 2 days before procedure
Who cannot join
- ABO blood group-incompatible renal allograft.
- Participant with a (non DSA) PRA > 20% within 6 months prior to transplant
- Persistent Leukopenia (WBC less than 2,000/mm3) or thrombocytopenia (<100,000/mm3).
- Seropositivity for HIV-1, hepatitis B core antigen, or hepatitis C virus (confirmed by hepatitis C virus RNA); or positivity for hepatitis B surface antigen.
- Active infection
- Left ventricular ejection fraction < 40% as determined by TTE or clinical evidence of heart failure
Show all 17Show fewer
- Forced expiratory volume FEV1 or DLCO < 50% of predicted.
- Lactation or pregnancy
- History of cancer (following the American Transplant Society Guidelines)
- Underlying renal disease etiology with a high risk of disease recurrence in the transplanted kidney (such as focal segmental glomerulosclerosis).
- Prior dose-limiting radiation therapy
- Known genetic disease or family history that may result in greater sensitivity to the effects of irradiation, or a physical deformity that would preclude adequate shielding or appropriate dosing during the irradiation component of the conditioning regimen
- Enrollment in other investigational drug studies within 30 days prior to enrollment
- Abnormal (>2 times lab normal) values for (a) liver function chemistries (ALT, AST, AP), (b) bilirubin, (c) coagulation studies (PT, PTT).
- Allergy or sensitivity to any component of Siplizumab, Fludarabine, Cyclophosphamide, tacrolimus, DMSO, MMF or rituximab.
- The presence of any medical condition that the investigator deems incompatible with participation in the trial.
- Subjects who have non-insulin dependent diabetes (NIDDM) without good blood glucose control (HbA1c<7). Subject with severe retinopathy, gastroparesis, or severe neuropathy which prevent subject's normal independent daily activities will be excluded from the study
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
The goal is to investigate the safety of the conditioning regimen, and its ability to induce donor/recipient lymphohematopoietic chimerism without Chimerism Transition Syndrome (CTS), which may result in donor-specific unresponsiveness (tolerance) to the renal allograft in the absence of maintenance immunosuppression.
- Conditions
- Renal Failure
- Being tested
- Rituximab, Fludarabine, Cyclophosphamide, Thymic irradiation and Siplizumab, Combined bone marrow and kidney transplant
- Medical subject headings
- Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rituximab, Fludarabine, Cyclophosphamide, Thymic irradiation and SiplizumabDrug
Conditioning regimen .Patients will receive Rituximab, Fludarabine, Cyclophosphamide, Thymic irradiation and Thymoglobulin
Combined bone marrow and kidney transplantProcedure or surgery
Recipients will receive a conditioning regimen that includes rituximab on study days -7 and -2, fludarabine 10mg/m2/day on days -6 to -3 (4 doses), cyclophosphamide (22.5mg/kg/day) on days -5 and -4, followed by local thymic irradiation (7 Gy) on day -1 and Siplizumabon days -1, 0, and +1. Combined kidney and bone marrow transplant will be performed on study day 0. Methylprednisolone will be started at 250 mg/day on day 0 and tapered to prednisone 20mg by day 10 after which it will be continued until day 20. Prophylaxis will be provided for hemorrhagic cystitis, PCP, fungal infection, CMV, and perioperative infection. All patients who require any blood transfusion will receive only leukocyte-depleted and irradiated blood products for a period of at least 52 weeks following transplantation. The proportion of patients successfully weaned off immunosuppression without chimerism transition syndrome (CTS) will be assessed.
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Transient Chimerism
Measured: 36 months after immunosuppression withdrawal
Incidence of Chimerism Transition Syndrome
Measured: 36 months after immunosuppression withdrawal
Incidence of tolerance induction
Measured: 36 months after immunosuppression withdrawal
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2020
- Study start1 Sep 2021
- Primary completionJan 2029 (estimated)
- Study completionJun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal FailureStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tatsuo Kawai, MD, PhD, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04540380
- Sponsor's protocol ID
- Tolerance SMC-MGH
- Status last verified
- Sep 2026
- First submitted
- 18 Aug 2020
- Last updated
- 28 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Renal Allograft Tolerance Through Mixed Chimerism - SMC/MGH
- ClinicalTrials.gov ID
- NCT04540380
- Acronym / sponsor ID
- Tolerance SMC-MGH
- Conditions
- Renal Failure
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 1 Sep 2021 (actual)
- Primary completion
- Jan 2029 (estimated)
- Study completion
- Jun 2029 (estimated)
- First posted
- 7 Sep 2020 (actual)
- 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.
The goal is to investigate the safety of the conditioning regimen, and its ability to induce donor/recipient lymphohematopoietic chimerism without Chimerism Transition Syndrome (CTS), which may result in donor-specific unresponsiveness (tolerance) to the renal allograft in the absence of maintenance immunosuppression.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female 18-65 years of age.
- Candidate for a living-donor renal allograft from an HLA mismatched donor
- Subjects with chronic kidney disease stage or ESRD who are treated with either hemodialysis or peritoneal dialysis.
- First transplant.
- Use of FDA-approved methods of contraception
Key exclusion criteria (17 listed)
- ABO blood group-incompatible renal allograft.
- Participant with a (non DSA) PRA > 20% within 6 months prior to transplant
- Persistent Leukopenia (WBC less than 2,000/mm3) or thrombocytopenia (<100,000/mm3).
- Seropositivity for HIV-1, hepatitis B core antigen, or hepatitis C virus (confirmed by hepatitis C virus RNA); or positivity for hepatitis B surface antigen.
- Active infection
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 |
|---|---|---|
| Rituximab, Fludarabine, Cyclophosphamide, Thymic irradiation and SiplizumabConditioning regimen .Patients will receive Rituximab, Fludarabine, Cyclophosphamide, Thymic irradiation and Thymoglobulin | Drug | – |
| Combined bone marrow and kidney transplantRecipients will receive a conditioning regimen that includes rituximab on study days -7 and -2, fludarabine 10mg/m2/day on days -6 to -3 (4 doses), cyclophosphamide (22.5mg/kg/day) on days -5 and -4, followed by local thymic irradiation (7 Gy) on day -1 and Siplizumabon days -1, 0, and +1. Combined kidney and bone marrow transplant will be performed on study day 0. Methylprednisolone will be started at 250 mg/day on day 0 and tapered to prednisone 20mg by day 10 after which it will be continued until day 20. Prophylaxis will be provided for hemorrhagic cystitis, PCP, fungal infection, CMV, and perioperative infection. All patients who require any blood transfusion will receive only leukocyte-depleted and irradiated blood products for a period of at least 52 weeks following transplantation. The proportion of patients successfully weaned off immunosuppression without chimerism transition syndrome (CTS) will be assessed. | Procedure or surgery | – |
Primary outcome
Incidence of Transient Chimerism
Time frame: 36 months after immunosuppression withdrawal
Incidence of Chimerism Transition Syndrome
Time frame: 36 months after immunosuppression withdrawal
Incidence of tolerance induction
Time frame: 36 months after immunosuppression withdrawal
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2026.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Rituximab, Fludarabine, Cyclophosphamide, Thymic irradiation and Siplizumab and Combined bone marrow and kidney transplant in people with Renal Failure, run by Massachusetts General Hospital 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 7 inclusion and 17 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: under way, not looking for participants, as of the sponsor's last update on 28 Sep 2026. 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?
This study is still under way. Results are not available in the source record yet.
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?
Incidence of Transient Chimerism (time frame: 36 months after immunosuppression withdrawal). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Sep 2026.