Optimization of NULOJIX® Usage Towards Minimizing CNI Exposure in Simultaneous Pancreas and Kidney Transplantation

Optimization of NULOJIX® (Belatacept) Usage as a Means of Minimizing CNI Exposure in Simultaneous Pancreas and Kidney Transplantation (CTOT-15)

The purpose of this study is to find out if the drug NULOJIX® (belatacept) will minimize the amount of other anti-rejection medications necessary and thereby reduce the long-term side effects caused by the other medications. The researchers also want to learn more about the safety of this treatment and long term health of transplanted pancreases and kidneys.

Study Overview

• Status: Terminated
• Conditions: Simultaneous Kidney and Pancreas Transplantation
• Intervention / Treatment: Drug: methylprednisolone; Biological: Anti-thymocyte Globulin (Rabbit); Drug: Tacrolimus; Drug: Mycophenolate mofetil; Biological: Belatacept

Detailed Description

Transplant recipients have to take anti-rejection medications to prevent their immune systems (the body's natural defense system against illness) from rejecting their new organs. Most patients who receive a transplanted organ must take these anti-rejection medications for the rest of their lives, or for as long as the transplanted organ continues to work. Taking standard anti-rejection medications for a long time can cause serious side effects, including pancreas and kidney damage. There would be a benefit to finding new anti-rejection medications that work just as well, but could lessen the amount of anti-rejection medications that are taken long term.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • San Francisco, California, United States, 94143-0780
      • University of California San Francisco Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Hospital
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ability to understand and provide written informed consent;
• Candidate for a primary simultaneous kidney and pancreas allograft with random c-peptide <0.3 ng/mL;
• No known contraindications to study therapy using NULOJIX® (belatacept);
• Female subjects of childbearing potential must have a negative pregnancy test upon study entry;
• Female and male participants with reproductive potential must agree to use FDA approved methods of birth control during participation in the study and for 4 months following study completion;
• No donor specific antibodies prior to transplant that are considered to be of clinical significance by the site investigator;
• Negative crossmatch, actual or virtual, or a Panel Reactive Antibodies (PRA) of 0% on historic and admission sera, as determined by each participating study center;
• A documented negative Tuberculosis (TB) test within the 12 months prior to transplant. If documentation is not present at the time of transplantation, and the subject does not have any risk factors for TB, a TB-specific interferon gamma release assay (IGRA) may be performed.

Exclusion Criteria:

• Need for multi-organ transplantation other than a kidney and pancreas;
• Recipient of previous organ transplant;
• Epstein-Barr Virus (EBV) sero-negative recipients or recipients whose EBV serostatus is unknown prior to the time of transplantation;
• Individuals infected by the hepatitis B or C viruses or HIV;
• Individuals who have required treatment with systemic prednisone or other immunosuppressive drugs within 1 year prior to transplant;
• Individuals previously treated with NULOJIX® (belatacept);
• Any condition that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements;
• Use of investigational drugs within 4 weeks of enrollment;
• Known hypersensitivity to mycophenolate mofetil (MMF)or any of the drug's components;
• Administration of live attenuated vaccine(s) within 8 weeks of enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Immunosuppression without Belatacept; Induction: 5 day course of methylprednisolone or equivalent;; Induction: Anti-thymocyte Globulin (Rabbit);; Maintenance Immunosuppression: Tacrolimus (or generic). The site investigator will identify a starting tacrolimus dose at his or her discretion, in order to achieve the target trough levels, no later than 5 days post-transplantation. Tacrolimus dosing will be initiated on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed, then adjusted to target trough levels of 8-12 ng/ml during the first 24 weeks post-transplant, then adjusted to target trough levels of 5-8 ng/ml thereafter.; Maintenance Immunosuppression: Mycophenolate mofetil (or Myfortic (mycophenolate sodium), or generic).	Drug: methylprednisolone; Other Names: Medrol; Biological: Anti-thymocyte Globulin (Rabbit); Other Names: Thymoglobulin; ATG (Rabbit); Drug: Tacrolimus; There may be an opportunity to withdraw tacrolimus at week 40; Other Names: Prograf; Drug: Mycophenolate mofetil; Mycophenolate mofetil will be administered at a target dose of 1000 mg by mouth twice daily (e.g., BID) beginning on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed (maximum MMF dosing is 2G per day). MMF will be adjusted based on clinical complications (such as neutropenia). Myfortic® (mycophenolate sodium) may be used as a replacement for MMF. Mycophenolate sodium will be dosed at 720 mg PO BID. Mycophenolate sodium will be adjusted based on clinical complications.; Other Names: MMF, mycophenolate sodium, CellCept
EXPERIMENTAL: Immunosuppression Including Belatacept; Induction: 5 day course of methylprednisolone or equivalent;; Induction: Anti-thymocyte Globulin (Rabbit);; Maintenance Immunosuppression: Belatacept; Maintenance Immunosuppression: Tacrolimus (or generic)- The site investigator will identify a starting tacrolimus dose at his or her discretion, in order to achieve the target trough levels no later than 5 days post-transplantation. Tacrolimus dosing will be initiated on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed. The dosage will be adjusted to achieve the following therapeutic trough levels: 5-8 ng/ml during the first 24 weeks post-transplant and then 3-5 ng/ml until day 280 (week 40). Subjects may be withdrawn if they meet all the criteria defined below.; Maintenance Immunosuppression: Mycophenolate mofetil (or Myfortic (mycophenolate sodium), or generic).	Drug: methylprednisolone; Other Names: Medrol; Biological: Anti-thymocyte Globulin (Rabbit); Other Names: Thymoglobulin; ATG (Rabbit); Drug: Tacrolimus; There may be an opportunity to withdraw tacrolimus at week 40; Other Names: Prograf; Drug: Mycophenolate mofetil; Mycophenolate mofetil will be administered at a target dose of 1000 mg by mouth twice daily (e.g., BID) beginning on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed (maximum MMF dosing is 2G per day). MMF will be adjusted based on clinical complications (such as neutropenia). Myfortic® (mycophenolate sodium) may be used as a replacement for MMF. Mycophenolate sodium will be dosed at 720 mg PO BID. Mycophenolate sodium will be adjusted based on clinical complications.; Other Names: MMF, mycophenolate sodium, CellCept; Biological: Belatacept; The first dose of belatacept will be administered approximately 24-48 hours after the last dose of Anti-Thymocyte Globulin (Rabbit).; Other Names: NULOJIX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Estimated Glomerular Filtration Rate (eGFR) Calculated for Each Treatment Group Using the CKD-EPI Equation at Wk 52 Post-Transplant	eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI): A score of ≥90 means kidney function is normal.; A score between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease.; Scores between 30 and 59 indicates moderately reduced kidney function.; Scores between 15 and 29 indicate severely reduced kidney function.; Scores below 15 indicate very severe or end stage kidney failure.	Week 52 Post-Transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Count of Participants With eGFR < 60 mL/Min/1.73 m^2 Measured by CKD-EPI at Wk 52 Post-Transplant	eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI): A score of ≥90 means kidney function is normal.; A score between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease.; Scores between 30 and 59 indicates moderately reduced kidney function.; Scores between 15 and 29 indicate severely reduced kidney function.; Scores below 15 indicate very severe or end stage kidney failure.	Week 52 Post-Transplant
Count of Participants by CKD Stage at Wk 52 Post-Transplant	The stages of Chronic Kidney Disease are defined using the participant's GFR value: Stage 1 if GFR value is ≥90 ( kidney function is normal); Stage 2 if 60 ≤ GFR < 90 (mildly reduced kidney function, pointing to kidney disease); Stage 3A if 45 ≤ GFR < 60*; Stage 3B if 30 ≤ GFR < 45*; Stage 4 if 15 ≤ GFR < 30 (severely reduced kidney function); Stage 5 if GFR < 15 (severe or end stage kidney failure). Stages 3A and 3B indicate moderately reduced kidney function.*	Week 52 Post-Transplant
Count of Participants With Defined CKD Stage 4 or 5 at Wk 52 Post-Transplant	The stages of Chronic Kidney Disease (CKD) are defined using the participant's GFR value: Stage 1 if GFR value is ≥ 90 (kidney function is normal); Stage 2 if 60 ≤ GFR < 90 (mildly reduced kidney function, pointing to kidney disease); Stage 3A if 45 <= GFR < 60*; Stage 3B if 30 <= GFR < 45*; Stage 4 if 15 ≤ GFR < 30 (severely reduced kidney function); Stage 5 if GFR < 15 (severe or end stage kidney failure). Stages 3A abd 3B indicate moderately reduced kidney function.*	Week 52 Post-Transplant
Mean Calculated eGFR Using MDRD 4 Variable Model at Wk 52 Post-Transplant	The estimated Glomerular Filtration Rate (eGFR) was calculated using the Modification of Diet in Renal Disease equation (MDRD): A score of ≥ 90 means kidney function is normal.; A score between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease.; Scores between 30 and 59 indicates moderately reduced kidney function.; Scores between 15 and 29 indicate severely reduced kidney function.; Scores below 15 indicate severe or endstage kidney failure.	Week 52 Post-Transplant
The Slope of eGFR by CKD-EPI Over Time Based on Serum Creatinine Post-Transplant	The estimated Glomerular Filtration Rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI): A score of ≥ 90 means kidney function is normal.; A score between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease.; Scores between 30 and 59 indicates moderately reduced kidney function.; Scores between 15 and 29 indicate severely reduced kidney function.; Scores below 15 indicate very severe or endstage kidney failure. An estimate of the slope, or change over time, in eGFR was produced using standard statistical linear modeling procedures. The estimate was then re-scaled so that it could be interpreted as a change in eGFR per month. Positive numbers indicate increasing kidney function. Larger numbers indicate greater change in kidney function.	Day 28 through Week 52 Post-Transplant
Count of Participants With Successful Discontinuation of Tacrolimus in Recipients Randomized to the Investigational Arm	Participants achieved successful discontinuation if they were able to discontinue (e.g., off tacrolimus therapy completely) over a 4-8 weeks after tacrolimus withdrawal was initiated at week 40.	Week 40 through week 48 Post-Transplant
Count of Participants With Delayed Graft Function at Wk 52 Post-Transplant	Delayed grafted function is defined as dialysis in the first week on one or more occasions for any indication other than the treatment of acute hyperkalemia in the setting of otherwise acceptable renal function.	Transplant through Week 52 Post-Transplant
Count of Participants With Full Pancreatic Graft Function (Insulin Independent) at Wk 52 Post-Transplant	Participants with full pancreatic graft functions are defined as those that no longer require exogenous insulin therapy.	Week 52 Post-Transplant
Count of Participants With Evidence of Partial Pancreatic Graft Function at Week 52 Post-Transplant	C-peptide is a measure of pancreatic function. The definition of partial pancreatic graft function: a fasting C-peptide levels >0.3ng.mL (0.1nmol.L) plus the participant's continued requirement for exogenous insulin or oral hypoglycemic agent(s).	Week 52 Post-Transplant
Count of Participants With Evidence of Pancreatic Loss at Week 52 Post-Transplant	C-peptide is a measure of pancreatic function. The definition of pancreatic loss: a C-peptide value of <0.3 ng/mL.	Week 52 Post-Transplant
HbA1c at Baseline (Pre-Transplant) Through Wk 52 Post-Transplant	Hemoglobin A1c (HbA1c) measures the average blood glucose levels over 8-12 weeks, thus acting as a useful long-term gauge of blood glucose control: A value below 6.0% reflects normal levels,; 6.0% to 6.4% reflects prediabetes, and; a value of ≥ 6.5% reflects diabetes.	Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52
Fasting Blood Sugar (FBS) From Baseline (Pre-Transplant) Through Wk 52 Post-Transplant	Fasting blood sugar (e.g., glucose) test is used to help diagnose diabetes, prediabetes, and gestational diabetes. Reference fasting blood sugar (glucose) values: 70 to 99 mg/dL is normal; 100 to 125 mg/dL is considered prediabetes; 126 mg/dL or higher on two separate tests is considered diabetes.	Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52
Standardized Blood Pressure Measurement From Baseline (Pre-Transplant) Through Wk 52 Post-Transplant	A blood pressure measurement consists of two numbers: the systolic and diastolic pressures. Systolic pressure measures the pressure in blood vessels when the heart beats. Diastolic pressure measures the pressure in blood vessels between beats of the heart.; Systolic measures of <120 and diastolic measures of <80 are considered normal.; Systolic measures of 120-139 and diastolic measures of 80-89 are considered at risk (or pre-hypertension).; Systolic measures of ≥140 and diastolic measures of ≥90 are considered high.	Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52
Count of Participants With Use of Anti-hypertensive Medication From Baseline (Pre-Transplant) Through Wk 52 Post-Transplant	Anti-hypertensive medications are a class of drugs that are used to treat hypertension. The medications seek to prevent the complications of high blood pressure, such as stoke and myocardial infarction.	Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52
Fasting Lipid Profile at Baseline (Pre-Transplant)	A fasting lipid profiles measures total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. These measurements are used in assessing one's risk of cardiovascular disease. Target ranges for each of these measures are provided: Total cholesterol: 75-169 mg/dL if age ≤20; 100-199 mg/dL if age ≥ 21; high values indicate risk of cardiovascular disease; LDL cholesterol: <70 mg/dL for people with documented cardiovascular disease or metabolic syndrome; <100 mg/dL for people considered high risk for cardiovascular disease; <130 mg/dL for people considered low risk for cardiovascular disease; high values indicate risk of cardiovascular disease; HDL cholesterol: 40mg/dL and higher; high values indicate reduced risk of cardiovascular disease; Non-HDL cholesterol: 30 mg/dL above the target value for LDL cholesterol; high values indicate risk of cardiovascular disease and; Triglycerides: <150 mg/dL; high values indicate risk of cardiovascular disease.	Baseline (Pre-Transplant)
Fasting Lipid Profile at Wk 28 Post-Transplant	A fasting lipid profiles measures total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. These measurements are used in assessing one's risk of cardiovascular disease. Target ranges for each of these measures are provided: Total cholesterol: 75-169 mg/dL if age ≤20; 100-199 mg/dL if age ≥ 21; high values indicate risk of cardiovascular disease; LDL cholesterol: <70 mg/dL for people with documented cardiovascular disease or metabolic syndrome; <100 mg/dL for people considered high risk for cardiovascular disease; <130 mg/dL for people considered low risk for cardiovascular disease; high values indicate risk of cardiovascular disease; HDL cholesterol: 40mg/dL and higher; high values indicate reduced risk of cardiovascular disease; Non-HDL cholesterol: 30 mg/dL above the target value for LDL cholesterol; high values indicate risk of cardiovascular disease and; Triglycerides: <150 mg/dL; high values indicate risk of cardiovascular disease.	Week 28 Post-Transplant
Lipid Profile at Wk 52 Post-Transplant	A fasting lipid profiles measures total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. These measurements are used in assessing one's risk of cardiovascular disease. Target ranges for each of these measures are provided: Total cholesterol: 75-169 mg/dL if age ≤ 20; 100-199 mg/dL if age ≥ 21; high values indicate risk of cardiovascular disease; LDL cholesterol: <70 mg/dL for people with documented cardiovascular disease or metabolic syndrome; <100 mg/dL for people considered high risk for cardiovascular disease; <130 mg/dL for people considered low risk for cardiovascular disease; high values indicate risk of cardiovascular disease; HDL cholesterol: 40mg/dL and higher; high values indicate reduced risk of cardiovascular disease; Non-HDL cholesterol: 30 mg/dL above the target value for LDL cholesterol; high values indicate risk of cardiovascular disease and; Triglycerides: <150 mg/dL; high values indicate risk of cardiovascular disease.	Week 52 Post-Transplant
Count of Participants With Use of Lipid Lowering Medications at Baseline, Wk 28 and Wk 52 Post-Transplant	Lipid lowering medications are used in the treatment of high levels of fats (lipids), such as cholesterol in blood	Baseline (Pre-Transplant), Week 28, and Week 52
Count of Participants With Acute Rejection (AR) of Kidney or Pancreatic Transplant During the First 52 Wks Post-Transplant	Biopsy-proven acute rejection (AR) of the kidney (renal) or pancreas during the first 52 weeks post-transplant. AR grading using standard Banff* criteria. For both kidney and pancreas, AR is defined as a grade ≥1.; AR for the kidney: Banff 2007 criteria. Severity of AR is graded by as IA, IB, IIA, IIB, or III, with IA defined as the mildest form of AR and III being the most severe.; AR for the pancreas: Banff 2011 Criteria. Severity of AR is graded as I, II, or III, with I defined as the mildest form of AR and III being the most severe.	Transplant through Week 52
Severity Grade of First Biopsy-Proven Acute Rejection (AR) During the First 52 Weeks Post-Transplant	AR grading using standard Banff* criteria. For both kidney and pancreas, AR is defined as a grade ≥1.; AR for the kidney: Banff 2007 criteria. Severity of AR is graded by as IA, IB, IIA, IIB, or III, with IA defined as the mildest form of AR and III being the most severe.; AR for the pancreas: Banff 2011 Criteria. Severity of AR is graded is I, II, or III, with I defined as the mildest form of AR and III being the most severe.	Transplant through Week 52
Count of Participants With Biopsy-Proven Humoral Rejection During the First 52 Weeks Post-Transplant	Humoral rejection (i.e., antibody mediated rejection) of: the kidney as defined by diffusely positive staining for C4d, presence of circulating anti-donor antibodies, and morphologic evidence of acute tissue injury determined by local pathology and,; the pancreas as defined by the presence of circulating anti-donor antibodies, and histopathological data including morphologic evidence of microvascular tissue injury and C4d staining in interacinar capillaries determined by local pathology.	Transplant through Week 52
Count of Participants With De Novo Anti-Donor Antibodies or Anti-Human Leukocyte Antigen (HLA) Antibodies During the First 52 Weeks Post-Transplant	The de novo development of donor-specific antibody (DSA) is associated with an increased risk of graft rejection. The presence of anti-Histocompatibility Antigen (HLA) antibodies (alloantibodies) is associated with increased risk of acute and chronic injury to the transplant allograft.	Transplant through Week 52
Type of Treatment(s) Participants Received for Biopsy-Proven Renal Allograft Rejection During the First 52 Weeks Post-Transplant	Participants are stratified by kidney biopsy results/treatment received. In the event of a for cause renal (kidney) biopsy: -The diagnosis of acute cellular rejection (ACR) using the Banff 2007 renal allograft pathology criteria. These criteria for renal allograft biopsies is an international histopathological classification standard. ACR is defined by a renal biopsy demonstrating a Banff 2007 classification of Grade IA or greater, with higher scores indicating more severe rejection. (Ref: Solez K, Colvin RB et al. Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant 2008 8(4): 753-60). Acronyms and abbreviations: ACR=Acute Cellular Rejection*; Normal*; Borderline* (criteria for ACR not fulfilled); Gd.=Grade*; IFTA=Interstitial Fibrosis and Tubular Atrophy*; ATG=Anti-thymocyte globulin therapy; IVIG=Intravenous Immunoglobulin therapy; PO=Orally; QD=Daily *Banff 2007 renal allograft pathology criteria	Transplant through Week 52
Type of Treatment(s) Participants Received for Biopsy-Proven Pancreatic Allograft Rejection During the First 52 Weeks Post-Transplant	Participants are stratified by kidney biopsy results/treatment received. Upon having a for-cause biopsy performed, persons often receive treatment for rejection based on the biopsy results, which may or may not reveal signs of rejection. Details of biopsy findings and corresponding treatment are provided for each instance of treatment for rejection. Results summary format: biopsy results; treatment. Acronyms and abbreviations: ACR=Acute Cellular Rejection; IFTA=Interstitial Fibrosis and Tubular Atrophy; ATG=Anti-thymocyte globulin therapy; IVIG=Intravenous Immunoglobulin therapy; Gd =Grade; PO=Orally; QD=Daily	Transplant through Week 52
Count of Participants With Event of Death, Graft Loss, or Undetectable C-peptide	This measure counts death, graft loss, or undetectable C-peptide value (e.g., C-peptide <0.3 ng/mL) occurring at any point post-transplant and independent of each other.; Kidney Graft Loss was defined as 90 consecutive days of dialysis dependency.; Pancreas graft loss was defined as returning to exogenous insulin therapy or initiation of oral hypoglycemic agents for greater than 30 days.; Factitious hypoglycemia due to surreptitious insulin administration results in elevated serum insulin levels and low or undetectable C-peptide levels.	Transplant through Week 52 Post-Transplant
Count of Participants With the Occurrence of Adverse Events (AEs) and Serious Adverse Events (SAEs)	Adverse events were collected systematically. Counts of all participants who experienced at least one adverse event (AEs, SAEs) by assigned treatment group. Refer to the Serious Adverse Events and Other Adverse Events tables for more detail.	From Enrollment (Pre-Transplant) to Week 52 Post-Transplant
Count of Participants With an Infectious Disease Serious Adverse Event(s) Requiring Hospitalization or Systemic Therapy	Infections were required to be reported as a serious adverse event if they required either inpatient hospitalization or prolongation of a current hospitalization. Displayed are counts of all participants who experienced infection(s) as an adverse event, by treatment group.	Transplant through Week 52 Post-Transplant
Count of Participant Diagnosed With BK Polyoma Virus (BKV) and Cytomegalovirus (CMV) Viremia As Adverse Events	Viral infections following renal transplantation is a significant source of recipient morbidity and mortality, and a significant cause of allograft dysfunction and loss. Specific viruses were monitored during this study using participant blood samples. Displayed are counts of participants who experienced BKV and CMV viremia as adverse events, diagnosed by test results from the local clinical pathology laboratory.	Transplant through Week 52 Post-Transplant
Count of Participants Diagnosed With Epstein-Barr Virus (EBV) Infection as an Adverse Event	Viral infections following renal transplantation is a significant source of recipient morbidity and mortality, and a significant cause of allograft dysfunction and loss. Specific viruses were monitored during this study using participant blood samples. Displayed are counts of all participants diagnosed with EBV infection as an adverse event by EBV test(s), diagnosed by test results from the local clinical pathology laboratory.	Transplant through Week 52 Post-Transplant
Count of Participants Diagnosed With Malignancy as an Adverse Event	An increased risk/incidence of malignancy is a recognized complication of immunosuppression in recipients of organ transplants. In Phase 3 clinical trials, overall malignancy rates were similar across all treatment groups, with the exception of posttransplant lymphoproliferative disease (PTLD).Displayed are counts of all participants who experienced malignancy reported as an adverse event.	Transplant through Week 52 Post-Transplant

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Bristol-Myers Squibb; Rho Federal Systems Division, Inc.; Clinical Trials in Organ Transplantation

Publications and helpful links

General Publications

• Stock PG, Mannon RB, Armstrong B, Watson N, Ikle D, Robien MA, Morrison Y, Odorico J, Fridell J, Mehta AK, Newell KA. Challenges of calcineurin inhibitor withdrawal following combined pancreas and kidney transplantation: Results of a prospective, randomized clinical trial. Am J Transplant. 2020 Jun;20(6):1668-1678. doi: 10.1111/ajt.15817. Epub 2020 Mar 8.

Helpful Links

• National Institute of Allergy and Infectious Diseases (NIAID) website
• Division of Allergy, Immunology, and Transplantation (DAIT) website
• Clinical Trials in Organ Transplantation (CTOT) website

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (ACTUAL): August 1, 2016
• Study Completion (ACTUAL): August 1, 2016

Study Registration Dates

• First Submitted: February 11, 2013
• First Submitted That Met QC Criteria: February 11, 2013
• First Posted (ESTIMATE): February 13, 2013

Study Record Updates

• Last Update Posted (ACTUAL): July 20, 2021
• Last Update Submitted That Met QC Criteria: June 30, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: immunosuppression; pancreas; transplantation; kidney; calcineurin inhibitor (CNI)
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuroprotective Agents; Protective Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Immune Checkpoint Inhibitors; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Methylprednisolone; Tacrolimus; Mycophenolic Acid; Abatacept; Thymoglobulin; Antilymphocyte Serum
• Other Study ID Numbers: DAIT CTOT-15; U01AI084150 (NIH); NIAID CRMS ID#: 20117 (OTHER: DAIT NIAID); SDY1433 (OTHER: ImmPort)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data is available in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
• IPD Sharing Time Frame: On average, data is available within 24 months after database lock for a trial.

IPD Sharing Access Criteria

Open access.

Study's:

• Accession ID is SDY1433, and
• Digital Object Identifier (DOI) is : 10.21430/M3CEH2A7ZF

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL