Kidney Failure, ChronicPhase 1NCT02314403

Renal Allograft Tolerance Through Mixed Chimerism (Belatacept)

A Phase 1 study testing Belatacept, ATG and Rituximab in people with Kidney Failure, Chronic and Renal Insufficiency, run by Massachusetts General Hospital 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

This study will examine the safety and effectiveness of a combination kidney and bone marrow transplant from a haplo-identical related donor. An investigational medication and other treatments will be given prior to and after the transplant to help protect the transplanted kidney from being attacked by the body's… Read more about this study

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Kidney Failure, Chronic, Renal Insufficiency
What is being tested?: Belatacept, ATG and Rituximab
Type of treatment: Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 2 participants
Where: 1 siteUnited States
Study dates: Feb 2015to Jul 2021
Phase: Phase 1
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

Male or female 18-60 years of age
Candidate for a living-donor renal allograft from an HLA mismatched donor
First or second transplant with either a living donor or cadaveric transplant as the first transplant.
Use of FDA-approved methods of contraception by all recipients from the time that study treatment begins until 104 weeks (24 months) after renal transplantation.
Ability to understand and provide informed consent.
Serologic evidence of prior exposure to EBV.

Who cannot join

ABO blood group-incompatible renal allograft.
Evidence of anti-HLA antibody within 60 days prior to transplant as assessed by routine methodology (AHG and/or ELISA)
Leukopenia or thrombocytopenia.
Positive for HIV-1, hepatitis B core antigen, or hepatitis C virus; or positivity for hepatitis B surface antigen.
Cardiac ejection fraction < 40% or clinical evidence of insufficiency.
Forced expiratory volume FEV1 < 50% of predicted.

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Lactation or pregnancy.
History of cancer other than basal cell carcinoma of the skin or carcinoma in situ of the cervix.
Underlying renal disease etiology with a high risk of disease recurrence in the transplanted kidney (such as focal segmental glomerulosclerosis, type I or II membranoprolifertive glomerulonephritis).
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 belatacept, ATG, tacrolimus, or rituximab.
Maintenance immunosuppression within 3 months prior to conditioning other than physiological doses of steroids, defined as ≤ 50 mg of hydrocortisone or dose equivalent.
The presence of any medical condition that the investigator deems incompatible with participation in the trial.

Trial locations and contacts

1 site in 1 country.

United States1 site

Massachusetts General Hospital
Boston, Massachusetts, 02114

Other trials in United States

About this study

Conditions: Kidney Failure, Chronic, Renal Insufficiency
Being tested: Belatacept, ATG, Rituximab, Total Body Irradiation, Thymic Irradiation
Keywords: ESRD
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.

BelataceptDrug
A selective T-cell (lymphocyte) costimulation blocker
ATGDrug
A T-Cell Depleting Agent
RituximabDrug
B-Cell Depleting Agent
Total Body IrradiationRadiation
Thymic IrradiationRadiation
Combined Bone Marrow/Kidney TransplantationProcedure or surgery

Study groups in NCT02314403
Study group	Role	What they receive
Combined Bone Marrow and Kidney Transplantation	Experimental	Recipients will receive a conditioning regimen that starts with Rituximab on day -7 (and days -2, 5, 12), Whole Body Irradiation 1.5 Gy x2 on study days -6 and -5, followed by ATG on Days -2, -1, 0. Belatacept 10mg/kg on Days 0, 3, 10, 17, 24, 38, 52. Thymic irradiation (7 Gy) will be given on study day -1, and combined renal and bone marrow transplant will be done on study day 0. Prednisone will be started at 2 mg/kg on day 4 and tapered off by day 20. Tacrolimus will be administered on study days -1 through 60, and then tapered if weaning criteria are met. Receives: Drug: Belatacept; Drug: ATG; Drug: Rituximab; Radiation: Total Body Irradiation; Radiation: Thymic Irradiation; Procedure: Combined Bone Marrow/Kidney Transplantation

What is being measured

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

Number of Participants With Successful Withdrawal of Immunosuppression
The Primary Outcome is: The induction of transient mixed chimerism and renal allograft tolerance (24 consecutive months off of immunosuppression)
Measured: 5 Years

Timeline

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

Feb 2015Jul 2021

First posted11 Dec 2014 (estimated)
Study startFeb 2015
Primary completionMar 2021
Study completionJul 2021

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.
Other trials for Kidney Failure, ChronicStudies 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 2 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02314403
Sponsor's protocol ID: MGH Tolerance Trial
Status last verified: Oct 2021
First submitted: 5 Dec 2014
Last updated: 25 Oct 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 25 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Renal Allograft Tolerance Through Mixed Chimerism (Belatacept)
ClinicalTrials.gov ID: NCT02314403
Acronym / sponsor ID: MGH Tolerance Trial
Conditions: Kidney Failure, Chronic, Renal Insufficiency
Keywords: ESRD
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 2 participants (actual)
Lead sponsor: Massachusetts General HospitalUniversity, hospital or other
Study start: Feb 2015
Primary completion: Mar 2021 (actual)
Study completion: Jul 2021 (actual)
First posted: 11 Dec 2014 (estimated)
Results: Posted 2 Sep 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Combined Bone Marrow and Kidney Transplantation	Experimental	Drug: Belatacept, Drug: ATG, Drug: Rituximab, Radiation: Total Body Irradiation, Radiation: Thymic Irradiation, Procedure: Combined Bone Marrow/Kidney TransplantationRecipients will receive a conditioning regimen that starts with Rituximab on day -7 (and days -2, 5, 12), Whole Body Irradiation 1.5 Gy x2 on study days -6 and -5, followed by ATG on Days -2, -1, 0. Belatacept 10mg/kg on Days 0, 3, 10, 17, 24, 38, 52. Thymic irradiation (7 Gy) will be given on study day -1, and combined renal and bone marrow transplant will be done on study day 0. Prednisone will be started at 2 mg/kg on day 4 and tapered off by day 20. Tacrolimus will be administered on study days -1 through 60, and then tapered if weaning criteria are met.

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (6 listed)

Male or female 18-60 years of age
Candidate for a living-donor renal allograft from an HLA mismatched donor
First or second transplant with either a living donor or cadaveric transplant as the first transplant.
Use of FDA-approved methods of contraception by all recipients from the time that study treatment begins until 104 weeks (24 months) after renal transplantation.
Ability to understand and provide informed consent.

Key exclusion criteria (16 listed)

ABO blood group-incompatible renal allograft.
Evidence of anti-HLA antibody within 60 days prior to transplant as assessed by routine methodology (AHG and/or ELISA)
Leukopenia or thrombocytopenia.
Positive for HIV-1, hepatitis B core antigen, or hepatitis C virus; or positivity for hepatitis B surface antigen.
Cardiac ejection fraction < 40% or clinical evidence of insufficiency.

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
BelataceptA selective T-cell (lymphocyte) costimulation blocker	Drug	Combined Bone Marrow and Kidney Transplantation
ATGA T-Cell Depleting Agent	Drug	Combined Bone Marrow and Kidney Transplantation
RituximabB-Cell Depleting Agent	Drug	Combined Bone Marrow and Kidney Transplantation
Total Body Irradiation	Radiation	Combined Bone Marrow and Kidney Transplantation
Thymic Irradiation	Radiation	Combined Bone Marrow and Kidney Transplantation
Combined Bone Marrow/Kidney Transplantation	Procedure or surgery	Combined Bone Marrow and Kidney Transplantation

Primary outcome

Number of Participants With Successful Withdrawal of Immunosuppression
Time frame: 5 Years
The Primary Outcome is: The induction of transient mixed chimerism and renal allograft tolerance (24 consecutive months off of immunosuppression)

Results and safety

Results posted to the registry on 2 Sep 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Combined Bone Marrow and Kidney Transplantation	2	2

Primary outcome: Number of Participants With Successful Withdrawal of Immunosuppression

Time frame: 5 Years. Count of participants. Unit: Participants

Measure	Combined Bone Marrow and Kidney Transplantation n = 2
Value	2

Population analysed: Two subjects underwent conditioning regimen

Adverse events

Time frame: 5 years. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Combined Bone Marrow and Kidney Transplantation	1 of 2 (50%)	2 of 2 (100%)	0 of 2

Limitations and caveats (from the sponsor): The incidence of adverse events found around 10 days after bone marrow transplant.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Kawai T, Cosimi AB, Sachs DH. Preclinical and clinical studies on the induction of renal allograft tolerance through transient mixed chimerism. Curr Opin Organ Transplant. 2011 Aug;16(4):366-71.Link provided by the sponsor.
Sachs DH, Sykes M, Kawai T, Cosimi AB. Immuno-intervention for the induction of transplantation tolerance through mixed chimerism. Semin Immunol. 2011 Jun;23(3):165-73.Link provided by the sponsor.
Kawai T, (et.al.) HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2008 Jan 24;358(4):353-61.Link 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.

Tatsuo Kawai, MD PhD 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 1 study testing Belatacept, ATG and Rituximab in people with Kidney Failure, Chronic and Renal Insufficiency, 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 6 inclusion and 16 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 25 Oct 2021. 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?

Yes. Results are posted in the registry (first posted 2 Sep 2021). 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 With Successful Withdrawal of Immunosuppression (time frame: 5 Years). 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 NCT02314403.

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 25 Oct 2021.