Use of Immune Globulin (IVIG) Plus Rituximab for Desensitization in Highly HLA Sensitized Patients Awaiting Deceased Donor Kidney Transplantation
Organ transplantation offers the only hope for a normal life for patients with end-stage renal disease on dialysis (ESRD). 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 to proceed.
In this study, the investigators propose to add an additional treatment (Rituxan), a humanized antibody directed at the CD20 antigen that is present on most B-cells (B-cells make antibodies, this Rituxan should help eliminate the source of anti-HLA by deleting the cells that make it).
Both IVIG and Rituxan are approved by the U.S. Food and Drug Administration (FDA) for numerous immunologic disorders and Non-Hodgkin's lymphoma, respectively. However, neither is yet approved by the FDA for desensitization of highly-HLA sensitized transplant patients.
Previously conducted pilot study demonstrated that IVIG + Rituxan can fill an important gap in our current therapeutic approach for management of highly sensitized patients and it may become the standard approach to manage these patients.
This study has been recently 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 dose 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 at 12 months. All subjects will have to complete 5 visits in a pre-transplant phase of the study. Patients who are transplanted will have additional 5 post-transplant visits. The following are research-related procedures:
- Rituxan infusion.
- Kidney allograft biopsy (Intra-op and 12 months post transplant)
- Rituxan level, HACA levels
- Immunologic biomarkers (CD19+, CD38+, CD27+)
Although Dr. Jordan 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 Rituxan and currently the study has been ammended to a safety and efficacy study focusing on decreasing HLA antibodies pre-transplant and minimizing DSA post transplant.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- Rates of transplantation [ Time Frame: 9 month ] [ Designated as safety issue: No ]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.
- Renal allograft survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- • Reduction in anti-HLA antibodies [ Time Frame: 9 months ] [ Designated as safety issue: No ]
- • The number of acute rejection episodes [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- • The number of serious infections [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
- • Adverse events, toxicity assessments [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||September 2013|
|Estimated Study Completion Date:||September 2015|
|Estimated Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
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.
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.
Other Name: Rituximab
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.
|Contact: Jua Choi, PharmD, RD, CSNCemail@example.com|
|Contact: Sabrina Louie, B.S.||firstname.lastname@example.org|
|United States, California|
|Cedars-Sinai Medical Center||Recruiting|
|Los Angeles, California, United States, 90048|
|Principal Investigator: Stanley Jordan, MD|
|Sub-Investigator: Ashley Vo, PharmD|
|Principal Investigator:||Stanley Jordan, MD||Cedars-Sinai Medical Center|