End Stage Renal Disease Clinical Trial
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.
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:
1. Rituximab infusion.
2. Kidney allograft biopsies (Intra-op, 12 months post-transplant)
3. Rituximab level, HACA levels
4. 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.
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