End Stage Renal DiseasePhase 1/2NCT01780454

Renal Allograft Tolerance Through Mixed Chimerism

A Phase 1/2 study testing MEDI-507, Rituximab and Total Body Irradiation in people with End Stage Renal Disease, 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 65 years
Conditions the study is for: End Stage Renal Disease
What is being tested?: MEDI-507, Rituximab and Total Body Irradiation
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: Mar 2013to Jun 2020
Phase: Phase 1/2
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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female 18-60 years of age
Candidate for a living-donor renal allograft with a one haplotype identical donor identified.
First or second transplant with either a living donor or cadaveric transplant as the first transplant.
Positive serologic testing for EBV indicating past exposure.

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)
Positive testing for: HIV, hepatitis B core antigen, or hepatitis C virus or positivity for hepatitis B surface antigen.
Cardiac ejection fraction < 40% or clinical evidence of insufficiency.
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 nonproliferative glomerulonephritis).

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Prior dose-limiting radiation therapy.
Abnormal (>2 times lab normal) values for (a) liver function chemistries (ALT, AST, AP), (b) bilirubin, (c) coagulation studies (PT, PTT).
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: End Stage Renal Disease
Being tested: MEDI-507, Rituximab, Total Body Irradiation, Thymic Irradiation
Keywords: End Stage Renal Disease, Renal Transplant, Bone Marrow Transplant, Tolerance, Chimerism, ESRD
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.

MEDI-507Drug
T-Cell Depleting Agent
RituximabDrug
B-Cell Depleting Agent
Total Body IrradiationRadiation
Bone Marrow Depletion
Thymic IrradiationRadiation

Study groups in NCT01780454
Study group	Role	What they receive
Combined Bone Marrow and Kidney Transplantation	Experimental	Conditioning regimen consisting of Rituximab, MEDI-507, Total Body Irradiation, Thymic Irradiation followed by simultaneous bone marrow and kidney transplantation Receives: Drug: MEDI-507; Drug: Rituximab; Radiation: Total Body Irradiation; Radiation: Thymic Irradiation

What is being measured

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

Successful Withdrawal of Immunosuppressive Therapy
The primary endpoint is induction of transient mixed chimerism and renal allograft tolerance without "engraftment syndrome" or "acute kidney injury"
Measured: 5 years

Secondary outcomes (1)

Number of Participants With Engraftment Syndrome
Constellation of symptoms known "Engraftment Syndrome"
Measured: 5 Years

Timeline

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

Mar 2013Jun 2020

First posted31 Jan 2013 (estimated)
Study startMar 2013
Primary completionJun 2018
Study completionJun 2020

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 (3)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 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 1/2
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: NCT01780454
Sponsor's protocol ID: 2013P000822
Status last verified: Mar 2021
First submitted: 29 Jan 2013
Last updated: 19 Apr 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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. doi: 10.1097/MOT.0b013e3283484b2c.
PubMed 21666482
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. doi: 10.1016/j.smim.2011.07.001. Epub 2011 Aug 11.
PubMed 21839648
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

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?

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Study at a glance

From the registry record, last updated by the sponsor on 19 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Renal Allograft Tolerance Through Mixed Chimerism
ClinicalTrials.gov ID: NCT01780454
Acronym / sponsor ID: 2013P000822
Conditions: End Stage Renal Disease
Keywords: End Stage Renal Disease, Renal Transplant, Bone Marrow Transplant, Tolerance, Chimerism, ESRD
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 2 participants (actual)
Lead sponsor: Massachusetts General HospitalUniversity, hospital or other
Study start: Mar 2013
Primary completion: Jun 2018 (actual)
Study completion: Jun 2020 (actual)
First posted: 31 Jan 2013 (estimated)
Results: Posted 23 Sep 2020

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: MEDI-507, Drug: Rituximab, Radiation: Total Body Irradiation, Radiation: Thymic IrradiationConditioning regimen consisting of Rituximab, MEDI-507, Total Body Irradiation, Thymic Irradiation followed by simultaneous bone marrow and kidney transplantation

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Male or female 18-60 years of age
Candidate for a living-donor renal allograft with a one haplotype identical donor identified.
First or second transplant with either a living donor or cadaveric transplant as the first transplant.
Positive serologic testing for EBV indicating past exposure.

Key exclusion criteria (9 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)
Positive testing for: HIV, hepatitis B core antigen, or hepatitis C virus or positivity for hepatitis B surface antigen.
Cardiac ejection fraction < 40% or clinical evidence of insufficiency.
History of cancer other than basal cell carcinoma of the skin or carcinoma in situ of the cervix.

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
MEDI-507T-Cell Depleting Agent	Drug	Combined Bone Marrow and Kidney Transplantation
RituximabB-Cell Depleting Agent	Drug	Combined Bone Marrow and Kidney Transplantation
Total Body IrradiationBone Marrow Depletion	Radiation	Combined Bone Marrow and Kidney Transplantation
Thymic Irradiation	Radiation	Combined Bone Marrow and Kidney Transplantation

Primary outcome

Successful Withdrawal of Immunosuppressive Therapy
Time frame: 5 years
The primary endpoint is induction of transient mixed chimerism and renal allograft tolerance without "engraftment syndrome" or "acute kidney injury"

1 secondary outcome

Number of Participants With Engraftment Syndrome
Time frame: 5 Years

Results and safety

Results posted to the registry on 23 Sep 2020, 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: Successful Withdrawal of Immunosuppressive Therapy

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

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

1 secondary outcome is reported in the full results.

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

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 21666482Kawai 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. doi: 10.1097/MOT.0b013e3283484b2c.
Background: PubMed 21839648Sachs 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. doi: 10.1016/j.smim.2011.07.001. Epub 2011 Aug 11.
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.

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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.

A. Benedict Cosimi, M.D. principal investigator

Massachusetts General Hospital

David Sachs, M.D. 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 1/2 study testing MEDI-507, Rituximab and Total Body Irradiation in people with End Stage Renal Disease, 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 4 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 19 Apr 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 combined 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.

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 23 Sep 2020). 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?

Successful Withdrawal of Immunosuppressive Therapy (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 NCT01780454, which also lists 3 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 19 Apr 2021.