Chronic RejectionPhase 1/2NCT00261547
Rituximab Treatment to Block HLA Antibodies in Renal Transplant Recipients
A Phase 1/2 study testing Rituximab in people with Chronic Rejection and Kidney Insufficiency, run by Massachusetts General Hospital.
Trial summary
The purpose of this study is to determine if administration of rituximab blocks the development of donor specific antibodies (DSA) in transplant recipients who have developed renal dysfunction and DSA after renal transplant. It is hoped that by blocking DSA production renal function will stabilize or improve. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Chronic Rejection, Kidney Insufficiency
- What is being tested?
- Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Dec 2005to Nov 2007
- Phase
- Phase 1/2
- 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 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Recipient of a primary cadaver or living donor renal allograft
- 18-64 years of age
- At least 6 months and no more than 10 years post renal transplant
- Serum clearly positive for defined DSA
- Renal biopsy positive for C4d staining within 28 days before study Day 1 treatment
- Blood positive for Cd 19/20 cells at greater than/equal to 50 % of lower limit of normal
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- Baseline serum creatinine 1.7-3.0 mg/dl
- On stable doses of tacrolimus and MMF for at least 1 month prior to study entry
- Able and willing to sign IRB approved consent form and comply with the requirements of the screen, treatment and follow-up phase of the protocol
- Negative serum pregnancy test (women of child bearing potential)
- Men and women of reproductive potential agree to use an acceptable method of birth control during treatment, for twelve months after treatment completion, or until B cell counts return to normal, whichever is longer
Who cannot join
- Hemoglobin: < 8.5 gm/dL
- Platelets: < 100.00/mm
- White blood cell count: < 3000/mm3
- AST or ALT . 2.5 x Upper Limit of Normal unless related to primary disease
- Positive Hepatitis B or C serology
- History of positive HIV
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- Treatment with any investigational agen within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer)
- Receipt of a live vaccine within 4 weeks prior to study entry
- Previous treatment with rituximab (rituxan)
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
- History of recurrent infections
- Known active bacterial, viral, fungal, mycobacterial or other infection or any major episode of infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
- Ongoing use of high dose steroids (>10mg/day) or unstable steroid dose in the past 4 weeks.
- Lack of peripheral venous access
- History of drug, alcohol or chemical abuse within 6 months prior to screen
- Pregnancy or lactation
- Concomitant malignancies or previous malignancies
- History of psychiatric disorder that would interfere with normal participation in this protocol
- Significant cardiac or pulmonary disease
- Any other disease, metabolic dysfunction, physical examination finding or clinical lab finding giving reasonable suspicion of disease or condition that contraindicates use of an investigational drug or that may affect the interpretation of the results or render subject a high rist from treatment complications
- Inability to comply with study and follow-up procedures
About this study
Official title: Pilot Study of Rituximab Treatment to Inhibit HLA Antibodies in Renal Allograft Recipients
The purpose of this study is to determine if administration of rituximab blocks the development of donor specific antibodies (DSA) in transplant recipients who have developed renal dysfunction and DSA after renal transplant. It is hoped that by blocking DSA production renal function will stabilize or improve.
Read the detailed description
A long established risk factor for late renal allograft loss is the development of DSA. Recent studies from our group and others have shown that these antibodies are probably responsible for chronic rejection by attacking the vascular endothelium and fixing complement (detected as C4d in renal biopsies). Studies in humans and monkeys have shown that circulating antibody and complement deposition precede the development of chronic graft injury. Interruption of antibody production is a potential beneficial strategy to prevent late graft loss from this mechanism.
Therapeutic regimens that have been used in an attempt to deplete HLA or ABO antibodies include plasmapheresis, IVIg, tacrolimus and mycophenolate mofetil (MMF), and anti-CD20 (rituximab). Of these regimens, the most specific is anti-CD20, rituximab (rituxan), a therapy now FDA approved for B cell proliferative diseases. Although initially introduced for the treatment of neoplasm, the humoral immunosuppressant effects of rituximab have been shown to have clinical significance. Rituximab interferes with both primary and secondary humoral responses by eliminating B-cells prior to antigen exposure, thus interfering with differentiation into antibody secreting cells and specific antibody production.
- Conditions
- Chronic Rejection, Kidney Insufficiency
- Being tested
- Rituximab
- Keywords
- Kidney transplantation, HLA
- Medical subject headings
- Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called Rituxan
All subjects will be treated with Rituximab 1000 mg (1 g) intravenously on days 1 and 15.
| Study group | Role | What they receive |
|---|---|---|
| Rituximab | Experimental | this study has only one arm as the treatment group Receives: Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Negative DSA by Luminex beads or ELISA
Measured: at 12 months post study medication
Lack of C4d deposition in peritubular capillary
Measured: on 12 month renal biopsy
Secondary outcomes (2)
Renal allograft function: Serum creatinine, Calculated creatinine clearance, Urine protein, Urine protein-creatinine ratio
Measured: 12 months after study entry compared to the baseline
Change in chronic rejection pathology indices
Measured: on 12-month renal biopsy compared to baseline biopsy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2005 (estimated)
- Study startDec 2005
- Primary completionNov 2007
- Study completionNov 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic RejectionStudies 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Principal investigator, Nina Tolkoff-Rubin, MD, Massachusetts General Hospital
- Investigators
- Nina Tolkoff-Rubin, M.D., Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00261547
- Sponsor's protocol ID
- 2005p001524
- Status last verified
- Oct 2023
- First submitted
- 1 Dec 2005
- Last updated
- 23 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Rituximab Treatment to Inhibit HLA Antibodies in Renal Allograft Recipients
- ClinicalTrials.gov ID
- NCT00261547
- Acronym / sponsor ID
- 2005p001524
- Conditions
- Chronic Rejection, Kidney Insufficiency
- Keywords
- Kidney transplantation, HLA
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Dec 2005
- Primary completion
- Nov 2007 (actual)
- Study completion
- Nov 2007 (actual)
- First posted
- 5 Dec 2005 (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.
The purpose of this study is to determine if administration of rituximab blocks the development of donor specific antibodies (DSA) in transplant recipients who have developed renal dysfunction and DSA after renal transplant. It is hoped that by blocking DSA production renal function will stabilize or improve.
Detailed description
A long established risk factor for late renal allograft loss is the development of DSA. Recent studies from our group and others have shown that these antibodies are probably responsible for chronic rejection by attacking the vascular endothelium and fixing complement (detected as C4d in renal biopsies). Studies in humans and monkeys have shown that circulating antibody and complement deposition precede the development of chronic graft injury. Interruption of antibody production is a potential beneficial strategy to prevent late graft loss from this mechanism.
Therapeutic regimens that have been used in an attempt to deplete HLA or ABO antibodies include plasmapheresis, IVIg, tacrolimus and mycophenolate mofetil (MMF), and anti-CD20 (rituximab). Of these regimens, the most specific is anti-CD20, rituximab (rituxan), a therapy now FDA approved for B cell proliferative diseases. Although initially introduced for the treatment of neoplasm, the humoral immunosuppressant effects of rituximab have been shown to have clinical significance. Rituximab interferes with both primary and secondary humoral responses by eliminating B-cells prior to antigen exposure, thus interfering with differentiation into antibody secreting cells and specific antibody production.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rituximab | Experimental | Drug: Rituximabthis study has only one arm as the treatment group |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Recipient of a primary cadaver or living donor renal allograft
- 18-64 years of age
- At least 6 months and no more than 10 years post renal transplant
- Serum clearly positive for defined DSA
- Renal biopsy positive for C4d staining within 28 days before study Day 1 treatment
Key exclusion criteria (21 listed)
- Hemoglobin: < 8.5 gm/dL
- Platelets: < 100.00/mm
- White blood cell count: < 3000/mm3
- AST or ALT . 2.5 x Upper Limit of Normal unless related to primary disease
- Positive Hepatitis B or C serology
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 |
|---|---|---|
| RituximabAlso: RituxanAll subjects will be treated with Rituximab 1000 mg (1 g) intravenously on days 1 and 15. | Drug | Rituximab |
Primary outcome
Negative DSA by Luminex beads or ELISA
Time frame: at 12 months post study medication
Lack of C4d deposition in peritubular capillary
Time frame: on 12 month renal biopsy
2 secondary outcomes
Renal allograft function: Serum creatinine, Calculated creatinine clearance, Urine protein, Urine protein-creatinine ratio
Time frame: 12 months after study entry compared to the baseline
Change in chronic rejection pathology indices
Time frame: on 12-month renal biopsy compared to baseline biopsy.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2023.
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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.
Nina Tolkoff-Rubin, M.D. principal investigator
Massachusetts General Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Rituximab in people with Chronic Rejection and Kidney Insufficiency, run by Massachusetts General Hospital.
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 11 inclusion and 21 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: withdrawn, as of the sponsor's last update on 23 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Negative DSA by Luminex beads or ELISA (time frame: at 12 months post study medication). The study lists 2 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 23 Oct 2023.