Trial Outcomes & Findings for Calcineurin Inhibitor (CNI)-Free Immunosuppressive Regimen in T1D Patients Receiving Islet Transplantation (NCT NCT01346085)

Last Updated: 2014-05-09

Results Overview

Insulin independence is defined as no need for exogenous insulin, with adequate glycemic control \[i.e., glycated hemoglobin \<7% (normal range 3.5 - 6.0%), fasting glucose levels not exceeding 140 mg/dL (7.8 mmol/L) more than three times per week and 2-hour postprandial levels not exceeding 180 mg/dL (10 mmol/L) more than four times per week\].

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

10 participants

Primary outcome timeframe

3 year

Results posted on

2014-05-09

Participant Flow

Participant milestones

Participant milestones
Measure	CNI-free Single-group CNI free immunosuppression: Immunosuppression consisted of: (i) pre-Tx rapamycin treatment (0.1 mg/kg/day) for at least 30 days; (ii) induction therapy with ATG (1.5 mg/kg/day for 4 days starting at day -1) and a steroid bolus (methyl-prednisolone 500 mg, day -1) plus low dose steroids (prednisone, 10 mg/day) and interleukin-1 (IL-1) receptor antagonist (100 mg/day) for 2 weeks (with ATG and steroid bolus administered only prior to the 1st islet infusion; (iii) maintenance with rapamycin (0.1 mg/kg/day) plus mycophenolate mofetil (2 g/day).
Overall Study STARTED	10
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Calcineurin Inhibitor (CNI)-Free Immunosuppressive Regimen in T1D Patients Receiving Islet Transplantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CNI-free Single-group n=10 Participants CNI free immunosuppression: Immunosuppression consisted of: (i) pre-Tx rapamycin treatment (0.1 mg/kg/day) for at least 30 days; (ii) induction therapy with ATG (1.5 mg/kg/day for 4 days starting at day -1) and a steroid bolus (methyl-prednisolone 500 mg, day -1) plus low dose steroids (prednisone, 10 mg/day) and interleukin-1 (IL-1) receptor antagonist (100 mg/day) for 2 weeks (with ATG and steroid bolus administered only prior to the 1st islet infusion; (iii) maintenance with rapamycin (0.1 mg/kg/day) plus mycophenolate mofetil (2 g/day).
Region of Enrollment Italy	8 participants n=5 Participants
Region of Enrollment Switzerland	2 participants n=5 Participants
Age, Continuous	39.6 years STANDARD_DEVIATION 4.94 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: 3 year

Outcome measures

Outcome measures
Measure	CNI-free Single-group n=10 Participants CNI free immunosuppression: Immunosuppression consisted of: (i) pre-Tx rapamycin treatment (0.1 mg/kg/day) for at least 30 days; (ii) induction therapy with ATG (1.5 mg/kg/day for 4 days starting at day -1) and a steroid bolus (methyl-prednisolone 500 mg, day -1) plus low dose steroids (prednisone, 10 mg/day) and interleukin-1 (IL-1) receptor antagonist (100 mg/day) for 2 weeks (with ATG and steroid bolus administered only prior to the 1st islet infusion; (iii) maintenance with rapamycin (0.1 mg/kg/day) plus mycophenolate mofetil (2 g/day).
The Proportion of Insulin Free Patients 3 Years After the Last Islet Infusion	4 participants

SECONDARY outcome

Timeframe: up to 3 years

Outcome measures

Outcome measures
Measure	CNI-free Single-group n=10 Participants CNI free immunosuppression: Immunosuppression consisted of: (i) pre-Tx rapamycin treatment (0.1 mg/kg/day) for at least 30 days; (ii) induction therapy with ATG (1.5 mg/kg/day for 4 days starting at day -1) and a steroid bolus (methyl-prednisolone 500 mg, day -1) plus low dose steroids (prednisone, 10 mg/day) and interleukin-1 (IL-1) receptor antagonist (100 mg/day) for 2 weeks (with ATG and steroid bolus administered only prior to the 1st islet infusion; (iii) maintenance with rapamycin (0.1 mg/kg/day) plus mycophenolate mofetil (2 g/day).
Insulin Independence With Adequate Glycemic Control Throughout Follow-up	4 participants

SECONDARY outcome

Timeframe: up to 3 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 3 year

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 3 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 3 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 3 years

Among study participants there were no reports of death, post-transplantation lymphoproliferative disease, cancer, or opportunistic infections. There was no evidence of cytomegalovirus disease, infection or serological activation (CMV early antigens negative during the whole follow-up), nor of Epstein-Barr clinical and serological reactivation (all patients were antibodies anti EBV positive before transplant, as per the inclusion criteria).

Outcome measures

Outcome data not reported

Adverse Events

CNI-free Single-group

Serious events: 8 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	CNI-free Single-group n=10 participants at risk CNI free immunosuppression: Immunosuppression consisted of: (i) pre-Tx rapamycin treatment (0.1 mg/kg/day) for at least 30 days; (ii) induction therapy with ATG (1.5 mg/kg/day for 4 days starting at day -1) and a steroid bolus (methyl-prednisolone 500 mg, day -1) plus low dose steroids (prednisone, 10 mg/day) and interleukin-1 (IL-1) receptor antagonist (100 mg/day) for 2 weeks (with ATG and steroid bolus administered only prior to the 1st islet infusion; (iii) maintenance with rapamycin (0.1 mg/kg/day) plus mycophenolate mofetil (2 g/day).
Immune system disorders Leucopenia	80.0% 8/10 • Number of events 8 • Up to 3 years after last islet infusion AEs were recorded according to the "Terminology Criteria for Adverse Events (TCAE) In Trials of Adult Pancreatic Islet Transplantation, Version 4.1 (16 July 2008)" (http://www.isletstudy.org/CITDocs/CIT-TCAE%20V4.pdf).
Immune system disorders Neutropenia	10.0% 1/10 • Number of events 1 • Up to 3 years after last islet infusion AEs were recorded according to the "Terminology Criteria for Adverse Events (TCAE) In Trials of Adult Pancreatic Islet Transplantation, Version 4.1 (16 July 2008)" (http://www.isletstudy.org/CITDocs/CIT-TCAE%20V4.pdf).
Blood and lymphatic system disorders Anemia	10.0% 1/10 • Number of events 1 • Up to 3 years after last islet infusion AEs were recorded according to the "Terminology Criteria for Adverse Events (TCAE) In Trials of Adult Pancreatic Islet Transplantation, Version 4.1 (16 July 2008)" (http://www.isletstudy.org/CITDocs/CIT-TCAE%20V4.pdf).
Gastrointestinal disorders Gastrointestinal conditions	20.0% 2/10 • Number of events 2 • Up to 3 years after last islet infusion AEs were recorded according to the "Terminology Criteria for Adverse Events (TCAE) In Trials of Adult Pancreatic Islet Transplantation, Version 4.1 (16 July 2008)" (http://www.isletstudy.org/CITDocs/CIT-TCAE%20V4.pdf).
Immune system disorders ATG reaction during third infusion	10.0% 1/10 • Number of events 1 • Up to 3 years after last islet infusion AEs were recorded according to the "Terminology Criteria for Adverse Events (TCAE) In Trials of Adult Pancreatic Islet Transplantation, Version 4.1 (16 July 2008)" (http://www.isletstudy.org/CITDocs/CIT-TCAE%20V4.pdf).

Other adverse events

Other adverse events
Measure	CNI-free Single-group n=10 participants at risk CNI free immunosuppression: Immunosuppression consisted of: (i) pre-Tx rapamycin treatment (0.1 mg/kg/day) for at least 30 days; (ii) induction therapy with ATG (1.5 mg/kg/day for 4 days starting at day -1) and a steroid bolus (methyl-prednisolone 500 mg, day -1) plus low dose steroids (prednisone, 10 mg/day) and interleukin-1 (IL-1) receptor antagonist (100 mg/day) for 2 weeks (with ATG and steroid bolus administered only prior to the 1st islet infusion; (iii) maintenance with rapamycin (0.1 mg/kg/day) plus mycophenolate mofetil (2 g/day).
Surgical and medical procedures Hemorrhage/bleeding from percutaneous transhepatic portal access	50.0% 5/10 • Number of events 6 • Up to 3 years after last islet infusion AEs were recorded according to the "Terminology Criteria for Adverse Events (TCAE) In Trials of Adult Pancreatic Islet Transplantation, Version 4.1 (16 July 2008)" (http://www.isletstudy.org/CITDocs/CIT-TCAE%20V4.pdf).
Gastrointestinal disorders Transient liver enzyme increase exceeding 5 times the baseline level	20.0% 2/10 • Number of events 2 • Up to 3 years after last islet infusion AEs were recorded according to the "Terminology Criteria for Adverse Events (TCAE) In Trials of Adult Pancreatic Islet Transplantation, Version 4.1 (16 July 2008)" (http://www.isletstudy.org/CITDocs/CIT-TCAE%20V4.pdf).
Immune system disorders Leucopenia	20.0% 2/10 • Number of events 2 • Up to 3 years after last islet infusion AEs were recorded according to the "Terminology Criteria for Adverse Events (TCAE) In Trials of Adult Pancreatic Islet Transplantation, Version 4.1 (16 July 2008)" (http://www.isletstudy.org/CITDocs/CIT-TCAE%20V4.pdf).
Gastrointestinal disorders Mouth ulcers	90.0% 9/10 • Number of events 9 • Up to 3 years after last islet infusion AEs were recorded according to the "Terminology Criteria for Adverse Events (TCAE) In Trials of Adult Pancreatic Islet Transplantation, Version 4.1 (16 July 2008)" (http://www.isletstudy.org/CITDocs/CIT-TCAE%20V4.pdf).
Immune system disorders Neutropenia	70.0% 7/10 • Number of events 7 • Up to 3 years after last islet infusion AEs were recorded according to the "Terminology Criteria for Adverse Events (TCAE) In Trials of Adult Pancreatic Islet Transplantation, Version 4.1 (16 July 2008)" (http://www.isletstudy.org/CITDocs/CIT-TCAE%20V4.pdf).
Blood and lymphatic system disorders Anemia	60.0% 6/10 • Number of events 6 • Up to 3 years after last islet infusion AEs were recorded according to the "Terminology Criteria for Adverse Events (TCAE) In Trials of Adult Pancreatic Islet Transplantation, Version 4.1 (16 July 2008)" (http://www.isletstudy.org/CITDocs/CIT-TCAE%20V4.pdf).
Skin and subcutaneous tissue disorders Acne or rash	60.0% 6/10 • Number of events 6 • Up to 3 years after last islet infusion AEs were recorded according to the "Terminology Criteria for Adverse Events (TCAE) In Trials of Adult Pancreatic Islet Transplantation, Version 4.1 (16 July 2008)" (http://www.isletstudy.org/CITDocs/CIT-TCAE%20V4.pdf).
Metabolism and nutrition disorders Hyperlipemia	40.0% 4/10 • Number of events 4 • Up to 3 years after last islet infusion AEs were recorded according to the "Terminology Criteria for Adverse Events (TCAE) In Trials of Adult Pancreatic Islet Transplantation, Version 4.1 (16 July 2008)" (http://www.isletstudy.org/CITDocs/CIT-TCAE%20V4.pdf).
Gastrointestinal disorders Gastrointestinal conditions	10.0% 1/10 • Number of events 1 • Up to 3 years after last islet infusion AEs were recorded according to the "Terminology Criteria for Adverse Events (TCAE) In Trials of Adult Pancreatic Islet Transplantation, Version 4.1 (16 July 2008)" (http://www.isletstudy.org/CITDocs/CIT-TCAE%20V4.pdf).
Infections and infestations Fungal infection	30.0% 3/10 • Number of events 3 • Up to 3 years after last islet infusion AEs were recorded according to the "Terminology Criteria for Adverse Events (TCAE) In Trials of Adult Pancreatic Islet Transplantation, Version 4.1 (16 July 2008)" (http://www.isletstudy.org/CITDocs/CIT-TCAE%20V4.pdf).
Musculoskeletal and connective tissue disorders Joint pain	20.0% 2/10 • Number of events 2 • Up to 3 years after last islet infusion AEs were recorded according to the "Terminology Criteria for Adverse Events (TCAE) In Trials of Adult Pancreatic Islet Transplantation, Version 4.1 (16 July 2008)" (http://www.isletstudy.org/CITDocs/CIT-TCAE%20V4.pdf).
Skin and subcutaneous tissue disorders Peripheral edema	20.0% 2/10 • Number of events 2 • Up to 3 years after last islet infusion AEs were recorded according to the "Terminology Criteria for Adverse Events (TCAE) In Trials of Adult Pancreatic Islet Transplantation, Version 4.1 (16 July 2008)" (http://www.isletstudy.org/CITDocs/CIT-TCAE%20V4.pdf).
Renal and urinary disorders Proteinuria	10.0% 1/10 • Number of events 1 • Up to 3 years after last islet infusion AEs were recorded according to the "Terminology Criteria for Adverse Events (TCAE) In Trials of Adult Pancreatic Islet Transplantation, Version 4.1 (16 July 2008)" (http://www.isletstudy.org/CITDocs/CIT-TCAE%20V4.pdf).
Cardiac disorders Hypertension	10.0% 1/10 • Number of events 1 • Up to 3 years after last islet infusion AEs were recorded according to the "Terminology Criteria for Adverse Events (TCAE) In Trials of Adult Pancreatic Islet Transplantation, Version 4.1 (16 July 2008)" (http://www.isletstudy.org/CITDocs/CIT-TCAE%20V4.pdf).
Infections and infestations Lower urinary tract infection	10.0% 1/10 • Number of events 1 • Up to 3 years after last islet infusion AEs were recorded according to the "Terminology Criteria for Adverse Events (TCAE) In Trials of Adult Pancreatic Islet Transplantation, Version 4.1 (16 July 2008)" (http://www.isletstudy.org/CITDocs/CIT-TCAE%20V4.pdf).
Infections and infestations Otitis externa	10.0% 1/10 • Number of events 1 • Up to 3 years after last islet infusion AEs were recorded according to the "Terminology Criteria for Adverse Events (TCAE) In Trials of Adult Pancreatic Islet Transplantation, Version 4.1 (16 July 2008)" (http://www.isletstudy.org/CITDocs/CIT-TCAE%20V4.pdf).

Additional Information

Dr Lorenzo Piemonti

Ospedale San Raffaele

Phone: +390226432706

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place