B-Lymphocyte Immunotherapy in Islet Transplantation: Toward Calcineurin-Inhibitor Free Immunosuppression (CIT-05/08)

General Description

The CIT consortium conducted a total of 9 studies across North America (CIT02 through CIT08) and the Nordic region (CIT01). CIT08 was a long-term follow-up study for interested participants at the North American sites. The target population was individuals with type 1 diabetes, normal kidney function, and intractable hypoglycemia. All studies treated participants with up to 3 separate infusions of islets. Subjects in CIT05 received, in an open label-fashion, the anti-CD20 agent rituximab in combination with rabbit anti-thymocyte globulin (ATG; daclizumab or basiliximab instead of ATG for the 2nd and 3rd transplants, if applicable) for induction and sirolimus alone for maintenance, a calcineurin-inhibitor free regimen.

Objectives

CIT-05: The primary objective is to determine the proportion of subjects who are insulin independent at 75 +/- 5 days following the first islet transplant among subjects treated with an experimental islet transplant immunosuppression regimen which includes rituximab and excludes tacrolimus. This group will be compared, as a secondary analysis, to subjects in a concurrent protocol, CIT-07, which uses a standard immunosuppressive regimen.

CIT-08: The primary objective is to provide extended follow-up for safety and efficacy and to support continued islet graft function to participants previously enrolled in CIT02, CIT03, CIT04, CIT05, CIT06, or CIT07.

Outcome Measure

The primary outcome measure was the proportion of participants with insulin independence at 75 days following the first transplant infusion. Secondary outcome measures included reduction in insulin requirements, mean amplitude of glycemic excursions, HbA1c levels, incidence of immune sensitization (defined by detected anti-HLA antibodies not present prior to transplantation), and quality of life.

Criteria

Individuals who met the following criteria were eligible for enrollment:

• Clinical history compatible with type 1 diabetes with onset at less than 40 years of age, insulin dependence for at least 5 years at study entry, and a sum of age and insulin dependent diabetes duration of at least 28

• Absent stimulated C-peptide (less than 0.3 ng/mL) 60 and 90 minutes post-mixed-meal tolerance test

• Involvement of intensive diabetes management, defined as: (1) Self-monitoring of glucose values no less than a mean of three times each day averaged over each week; (2) Administration of three or more insulin injections each day or insulin pump therapy; (3) Under the direction of an endocrinologist, diabetologist, or diabetes specialist with at least three evaluations during the 12 months prior to study enrollment

• At least one episode of severe hypoglycemia in the 12 months prior to study enrollment

• Reduced awareness of hypoglycemia.

Exclusion criteria are documented in the study protocol.

Outcome

This study was terminated for lack of efficacy.