End Stage Renal DiseasePhase 1/2NCT01178216
Use of Immune Globulin Plus Rituximab for Desensitization in Highly HLA Sensitized Patients Awaiting Deceased Donor Kidney Transplantation
A Phase 1/2 study testing Rituxan in people with End Stage Renal Disease, run by Stanley Jordan, MD at 1 site in United States.
Trial summary
This single center, Phase I/II, exploratory study has been modified to a safety/efficacy study providing all patients with IVIG and Rituximab. The trial will examine the safety and efficacy of human polyclonal IVIG 10%, when given at [2.0 gm/kgx2], + Rituximab 1gm to reduce donor-specific antibodies (DSA) to a level… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- End Stage Renal Disease
- What is being tested?
- Rituxan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2013to 28 Jul 2017
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- End-stage renal disease.
- No known contraindications for therapy with IGIV10%/Rituximab.
- Age 18-70 years at the time of screening.
- PRA> 30% demonstrated on 3 consecutive samples, UNOS wait time sufficient to allow DD offers, history of sensitizing events, positive crossmatch with the intended donor.
- Subject/Parent/Guardian must be able to understand and provide informed consent.
Who cannot join
- Lactating or pregnant females.
- Pediatric patients <18 years of age
- Women of child-bearing age who are not willing or able to practice FDA-approved forms of contraception.
- HIV-positive subjects.
- Subjects who test positive for HBV infection [positive HBVsAg, HBVcAg, or HBVeAg/DNA] or HCV infection [positive Anti-HCV (EIA) and confirmatory HCV RIBA].
- Subjects with active TB.
Show all 24Show fewer
- Subjects with selective IgA deficiency, those who have known anti-IgA antibodies, and those with a history of anaphylaxis or severe systemic responses to any part of the clinical trial material.
- Subjects who have received or for whom multiple organ transplants are planned.
- Recent recipients of any licensed or investigational live attenuated vaccine(s) within two months of the screening visit (including but not limited to any of the following:
- Adenovirus [Adenovirus vaccine live oral type 7]
- Varicella [Varivax]
- Hepatitis A [VAQTA]
- Rotavirus [Rotashield]
- Yellow fever [Y-F-Vax]
- Measles and mumps [Measles and mumps virus vaccine live]
- Measles, mumps, and rubella vaccine [M-M-R-II]
- Sabin oral polio vaccine
- Rabies vaccines [IMOVAX Rabies I.D., RabAvert])
- A significantly abnormal general serum screening lab result defined as a WBC < 3.0 X 103/ml, a Hgb < 8.0 g/dL, a platelet count < 100 X 103/ml, , an SGOT > 5X upper limit of normal, and an SGPT >5X upper limit of normal range.
- Individuals deemed unable to comply with the protocol.
- Subjects with active CMV or EBV infection as defined by CMV-specific serology (IgG or IgM) and confirmed by quantitative PCR with or without a compatible illness.
- Subjects with a known history of previous myocardial infarction within one year of screening.
- Subjects with a history of clinically significant thrombotic episodes, and subjects with active peripheral vascular disease.
- Use of investigational agents within 4 weeks of participation.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cedars-Sinai Medical Center
Los Angeles, California, 90048
About this study
Official title: Use of Immune Globulin Intravenous (Human), 10% (IVIG), Plus Rituximab as Agents to Reduce Donor Specific Antibodies, Improve Transplant Rates and Outcomes in Highly-HLA Sensitized Patients Awaiting Deceased Donor Kidney Transplantation
This single center, Phase I/II, exploratory study has been modified to a safety/efficacy study providing all patients with IVIG and Rituximab. The trial will examine the safety and efficacy of human polyclonal IVIG 10%, when given at [2.0 gm/kgx2], + Rituximab 1gm to reduce donor-specific antibodies (DSA) to a level that is permissive for transplantation in 75 subjects (adults only ages >18 yrs) who are highly-HLA sensitized and are awaiting deceased donor kidney transplant. Once transplant offers are entertained, a donor-specific crossmatch will be performed. If acceptable crossmatches and DSA levels are seen, the patients will proceed to DD transplantation. Patients receiving transplants will receive an additional dose of IVIG at transplantation (within 10 days) and will receive additional doses of Rituximab 1g at 3M post transplant if DSA levels remain or become positive at 6M if de novo DSA occur. Patients who are desensitized and not transplanted at 9M after desensitization will have completed the study and can be treated as best judged by their physician.
Read the detailed description
Organ transplantation offers the only hope for a normal life for patients with end-stage renal disease on dialysis. For patients with antibodies to human leukocyte antigens (HLA), transplantation is extremely difficult or impossible since pre-formed antibodies will cause severe rejection and loss of transplanted organs. Intravenous gamma globulin (IVIG) can reduce or eliminate these antibodies in most patients and allow for successful transplantation. This breakthrough has allowed patients previously considered not transplantable to receive life-saving transplants. However, IVIG alone does not always eradicate the anti-HLA antibodies to a degree that will allow transplantation.
In this study, the investigators propose additional treatment with rituximab, a humanized antibody directed at the CD20 antigen that is present on most B-cells. Both IVIG and rituximab are approved by the U.S. Food and Drug Administration (FDA) for numerous immunologic disorders and Non-Hodgkin's lymphoma, respectively. However, neither is approved by the FDA for desensitization of highly-HLA sensitized transplant patients. A previously conducted pilot study demonstrated IVIG + Rituximab can fill an important gap in the current therapeutic approach for management of highly sensitized patients and may become the standard therapy.
Update: Study updated after observation that subjects transplanted after desensitization with IVIG alone experienced higher rates of antibody rejection and graft loss. The primary objective of this revised protocol will be to examine the safety and efficacy of IVIG 2gm/kg (maximum 140g) given on day#0 \& day #30 plus Rituximab 1gm given on day #15. Transplanted patients will receive additional doses of Rituximab 1gm at 3 months post-transplant if donor specific antibody (DSA) levels remain or become positive or at 6M if de novo DSA occur. All transplanted patients who remain DSA negative, will not receive additional Rituximab. All transplanted patients will have a protocol biopsy at transplant and 12 months. All subjects will complete 5 visits in the pre-transplant phase of the study. Patients who are transplanted will have additional 5 post-transplant visits. The following are research-related procedures:
- Rituximab infusion.
- Kidney allograft biopsies (Intra-op, 12 months post-transplant)
- Rituximab level, HACA levels
- Immunologic biomarkers (CD19+, CD38+, CD27+)
Although the investigator commonly uses both treatment regimens at Cedars-Sinai Medical Center, only the IVIG treatment is considered to be standard of care for highly HLA-sensitized patients. The investigational component of this study is the addition of the rituximab. Currently the study has been amended to a safety and efficacy study focusing on decreasing HLA antibodies pre-transplant and minimizing DSA post-transplant.
- Conditions
- End Stage Renal Disease
- Being tested
- Rituxan
- Keywords
- Kidney transplant, highly sensitized
- 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.
RituxanBiological
Also called Rituximab
Rituximab (1gm) given on day# 15. Transplanted patients will receive an additional dose of Rituximab at 3M if DSA remains or 6M if denovo DSA present.
| Study group | Role | What they receive |
|---|---|---|
| Rituxan | Experimental | All study patients will receive Rituxan 1g on day 15 from start of desensitization and either 3M or 6M post transplant depending on the presence of DSA. Receives: Biological: Rituxan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients That Underwent Transplantation
This trial is designed to determine if Rituximab + IVIG can improve rates of transplantation for highly-HLA sensitized DD candidates on the UNOS waiting list over a 9M period of time after completion of treatment.
Measured: 9 month
Secondary outcomes (5)
Number of Patients With Allograft Survival
Graft survival in study participants
Measured: 12 months
Reduction in Anti-HLA Antibodies
Number of patients with a reduction in anti-HLA antibodies.
Measured: 9 months
Number of Acute Rejection Episodes
Number of rejection episodes in study participants
Measured: 12 months
Number of Patients Reporting a Serious Infection
Infection rate in study participants
Measured: 12 months
Number of Adverse Events, Toxicity Assessments
Adverse effects in study participants
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2010 (estimated)
- Study startSep 2013
- Primary completion28 Jul 2017
- Study completion28 Jul 2017
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 (2)Papers the sponsor has linked to this study.
- Other trials for End Stage Renal DiseaseStudies of the same condition, open and under way.
- 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
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanley Jordan, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor-investigator, Stanley Jordan, MD, Cedars-Sinai Medical Center
- Investigators
- Stanley Jordan, MD, Principal investigator, Cedars-Sinai Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01178216
- Sponsor's protocol ID
- Genentech-Ritux2010
- Status last verified
- Sep 2018
- First submitted
- 9 Aug 2010
- Last updated
- 26 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Jordan SC, Peng A, Vo AA. Therapeutic strategies in management of the highly HLA-sensitized and ABO-incompatible transplant recipients. Contrib Nephrol. 2009;162:13-26. doi: 10.1159/000170864. Epub 2008 Oct 31.
PubMed 19001810Vo AA, Lukovsky M, Toyoda M, Wang J, Reinsmoen NL, Lai CH, Peng A, Villicana R, Jordan SC. Rituximab and intravenous immune globulin for desensitization during renal transplantation. N Engl J Med. 2008 Jul 17;359(3):242-51. doi: 10.1056/NEJMoa0707894.
PubMed 18635429
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Immune Globulin Intravenous (Human), 10% (IVIG), Plus Rituximab as Agents to Reduce Donor Specific Antibodies, Improve Transplant Rates and Outcomes in Highly-HLA Sensitized Patients Awaiting Deceased Donor Kidney Transplantation
- ClinicalTrials.gov ID
- NCT01178216
- Acronym / sponsor ID
- Genentech-Ritux2010
- Conditions
- End Stage Renal Disease
- Keywords
- Kidney transplant, highly sensitized
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Stanley Jordan, MDUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Sep 2013
- Primary completion
- 28 Jul 2017 (actual)
- Study completion
- 28 Jul 2017 (actual)
- First posted
- 10 Aug 2010 (estimated)
- Results
- Posted 7 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This single center, Phase I/II, exploratory study has been modified to a safety/efficacy study providing all patients with IVIG and Rituximab. The trial will examine the safety and efficacy of human polyclonal IVIG 10%, when given at [2.0 gm/kgx2], + Rituximab 1gm to reduce donor-specific antibodies (DSA) to a level that is permissive for transplantation in 75 subjects (adults only ages >18 yrs) who are highly-HLA sensitized and are awaiting deceased donor kidney transplant. Once transplant offers are entertained, a donor-specific crossmatch will be performed. If acceptable crossmatches and DSA levels are seen, the patients will proceed to DD transplantation. Patients receiving transplants will receive an additional dose of IVIG at transplantation (within 10 days) and will receive additional doses of Rituximab 1g at 3M post transplant if DSA levels remain or become positive at 6M if de novo DSA occur. Patients who are desensitized and not transplanted at 9M after desensitization will have completed the study and can be treated as best judged by their physician.
Detailed description
Organ transplantation offers the only hope for a normal life for patients with end-stage renal disease on dialysis. For patients with antibodies to human leukocyte antigens (HLA), transplantation is extremely difficult or impossible since pre-formed antibodies will cause severe rejection and loss of transplanted organs. Intravenous gamma globulin (IVIG) can reduce or eliminate these antibodies in most patients and allow for successful transplantation. This breakthrough has allowed patients previously considered not transplantable to receive life-saving transplants. However, IVIG alone does not always eradicate the anti-HLA antibodies to a degree that will allow transplantation.
In this study, the investigators propose additional treatment with rituximab, a humanized antibody directed at the CD20 antigen that is present on most B-cells. Both IVIG and rituximab are approved by the U.S. Food and Drug Administration (FDA) for numerous immunologic disorders and Non-Hodgkin's lymphoma, respectively. However, neither is approved by the FDA for desensitization of highly-HLA sensitized transplant patients. A previously conducted pilot study demonstrated IVIG + Rituximab can fill an important gap in the current therapeutic approach for management of highly sensitized patients and may become the standard therapy.
Update: Study updated after observation that subjects transplanted after desensitization with IVIG alone experienced higher rates of antibody rejection and graft loss. The primary objective of this revised protocol will be to examine the safety and efficacy of IVIG 2gm/kg (maximum 140g) given on day#0 \& day #30 plus Rituximab 1gm given on day #15. Transplanted patients will receive additional doses of Rituximab 1gm at 3 months post-transplant if donor specific antibody (DSA) levels remain or become positive or at 6M if de novo DSA occur. All transplanted patients who remain DSA negative, will not receive additional Rituximab. All transplanted patients will have a protocol biopsy at transplant and 12 months. All subjects will complete 5 visits in the pre-transplant phase of the study. Patients who are transplanted will have additional 5 post-transplant visits. The following are research-related procedures:
- Rituximab infusion.
- Kidney allograft biopsies (Intra-op, 12 months post-transplant)
- Rituximab level, HACA levels
- Immunologic biomarkers (CD19+, CD38+, CD27+)
Although the investigator commonly uses both treatment regimens at Cedars-Sinai Medical Center, only the IVIG treatment is considered to be standard of care for highly HLA-sensitized patients. The investigational component of this study is the addition of the rituximab. Currently the study has been amended to a safety and efficacy study focusing on decreasing HLA antibodies pre-transplant and minimizing DSA post-transplant.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rituxan | Experimental | Biological: RituxanAll study patients will receive Rituxan 1g on day 15 from start of desensitization and either 3M or 6M post transplant depending on the presence of DSA. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- End-stage renal disease.
- No known contraindications for therapy with IGIV10%/Rituximab.
- Age 18-70 years at the time of screening.
- PRA> 30% demonstrated on 3 consecutive samples, UNOS wait time sufficient to allow DD offers, history of sensitizing events, positive crossmatch with the intended donor.
- Subject/Parent/Guardian must be able to understand and provide informed consent.
Key exclusion criteria (24 listed)
- Lactating or pregnant females.
- Pediatric patients <18 years of age
- Women of child-bearing age who are not willing or able to practice FDA-approved forms of contraception.
- HIV-positive subjects.
- Subjects who test positive for HBV infection [positive HBVsAg, HBVcAg, or HBVeAg/DNA] or HCV infection [positive Anti-HCV (EIA) and confirmatory HCV RIBA].
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 |
|---|---|---|
| RituxanAlso: RituximabRituximab (1gm) given on day# 15. Transplanted patients will receive an additional dose of Rituximab at 3M if DSA remains or 6M if denovo DSA present. | Biological | Rituxan |
Primary outcome
Number of Patients That Underwent Transplantation
Time frame: 9 month
This trial is designed to determine if Rituximab + IVIG can improve rates of transplantation for highly-HLA sensitized DD candidates on the UNOS waiting list over a 9M period of time after completion of treatment.
5 secondary outcomes
Number of Patients With Allograft Survival
Time frame: 12 months
Reduction in Anti-HLA Antibodies
Time frame: 9 months
Number of Acute Rejection Episodes
Time frame: 12 months
Number of Patients Reporting a Serious Infection
Time frame: 12 months
Number of Adverse Events, Toxicity Assessments
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19001810Jordan SC, Peng A, Vo AA. Therapeutic strategies in management of the highly HLA-sensitized and ABO-incompatible transplant recipients. Contrib Nephrol. 2009;162:13-26. doi: 10.1159/000170864. Epub 2008 Oct 31.
- Background: PubMed 18635429Vo AA, Lukovsky M, Toyoda M, Wang J, Reinsmoen NL, Lai CH, Peng A, Villicana R, Jordan SC. Rituximab and intravenous immune globulin for desensitization during renal transplantation. N Engl J Med. 2008 Jul 17;359(3):242-51. doi: 10.1056/NEJMoa0707894.
- Cedars-Sinai Medical Center Kidney Transplant 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.
Stanley Jordan, MD principal investigator
Cedars-Sinai Medical Center
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 Rituxan in people with End Stage Renal Disease, run by Stanley Jordan, MD 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 5 inclusion and 24 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 26 Oct 2018. 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 7 Sep 2018). 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 Patients That Underwent Transplantation (time frame: 9 month). 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 NCT01178216, which also lists 2 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 26 Oct 2018.