Use of Immune Globulin Plus Rituximab for Desensitization in Highly HLA Sensitized Patients Awaiting Deceased Donor Kidney Transplantation
|ClinicalTrials.gov Identifier: NCT01178216|
Recruitment Status : Completed
First Posted : August 10, 2010
Last Update Posted : December 27, 2017
|Condition or disease||Intervention/treatment||Phase|
|End Stage Renal Disease||Biological: Rituxan||Phase 1 Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||41 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||September 2013|
|Primary Completion Date :||July 28, 2017|
|Study Completion Date :||July 28, 2017|
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
- Rates of 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.
- Renal allograft survival [ Time Frame: 12 months ]Graft survival in study participants
- Reduction in anti-HLA antibodies [ Time Frame: 9 months ]Antibody measurements at multiple time points
- Incidence of acute rejection episodes [ Time Frame: 12 months ]Number of rejection episodes in study participants
- Incidence of serious infections [ Time Frame: 12 months ]Infection rate in study participants
- Adverse events, toxicity assessments [ Time Frame: 12 months ]Adverse effects in study participants
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01178216
|United States, California|
|Cedars-Sinai Medical Center|
|Los Angeles, California, United States, 90048|
|Principal Investigator:||Stanley Jordan, MD||Cedars-Sinai Medical Center|