Use of Immune Globulin Plus Rituximab for Desensitization in Highly HLA Sensitized Patients Awaiting Deceased Donor Kidney Transplantation

NCT01178216 | Completed Phase 1 Results

• 1 other identifier: Genentech-Ritux2010
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

End Stage Renal Disease

Keywords

Kidney transplant; highly sensitized

Outcome Measures

Primary Outcomes (1)

• 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.

  9 month

Secondary Outcomes (5)

• Number of Patients With Allograft Survival

  12 months

• Reduction in Anti-HLA Antibodies

  9 months

• Number of Acute Rejection Episodes

  12 months

• Number of Patients Reporting a Serious Infection

  12 months

• Number of Adverse Events, Toxicity Assessments

  12 months

Study Arms (1)

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.

Biological: Rituxan

Interventions

Rituxan BIOLOGICAL

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.

Also known as: Rituximab

Rituxan

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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 \[Measles and mumps virus vaccine live\]

Sponsors & Collaborators

• Stanley Jordan, MD: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Related Publications (2)

• 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.

  PMID: 19001810 BACKGROUND

• Vo 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.

  PMID: 18635429 BACKGROUND

Related Links

• Cedars-Sinai Medical Center Kidney Transplant Website

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Noriko Ammerman, PharmD
• Organization: Cedars-Sinai Medical Center

noriko.ammerman@cshs.org

3102488186

Study Officials

• Stanley Jordan, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Director, Medical Director, Renal Transplantation & Transplant Immunotherpay

Study Record Dates

• First Submitted: August 9, 2010
• First Posted: August 10, 2010
• Study Start: September 1, 2013
• Primary Completion: July 28, 2017
• Study Completion: July 28, 2017
• Last Updated: October 26, 2018
• Results First Posted: September 7, 2018

Record last verified: 2018-09

Locations

US (1)