Trial Outcomes & Findings for Renal Allograft Tolerance Through Mixed Chimerism (Belatacept) (NCT NCT02314403)

NCT ID: NCT02314403

Last Updated: 2021-10-25

Results Overview

The Primary Outcome is: The induction of transient mixed chimerism and renal allograft tolerance (24 consecutive months off of immunosuppression)

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 2 participants
• Primary outcome timeframe: 5 Years
• Results posted on: 2021-10-25

Participant Flow

Participant milestones

Measure	Combined Bone Marrow and Kidney Transplantation Recipients will receive a conditioning regimen that starts with Rituximab on day -7 (and days -2, 5, 12), Whole Body Irradiation 1.5 Gy x2 on study days -6 and -5, followed by ATG on Days -2, -1, 0. Belatacept 10mg/kg on Days 0, 3, 10, 17, 24, 38, 52. Thymic irradiation (7 Gy) will be given on study day -1, and combined renal and bone marrow transplant will be done on study day 0. Prednisone will be started at 2 mg/kg on day 4 and tapered off by day 20. Tacrolimus will be administered on study days -1 through 60, and then tapered if weaning criteria are met. Belatacept: A selective T-cell (lymphocyte) costimulation blocker ATG: A T-Cell Depleting Agent Rituximab: B-Cell Depleting Agent Total Body Irradiation Thymic Irradiation Combined Bone Marrow/Kidney Transplantation
Overall Study STARTED	2
Overall Study COMPLETED	2
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Renal Allograft Tolerance Through Mixed Chimerism (Belatacept)

Baseline characteristics by cohort

Measure	Combined Bone Marrow and Kidney Transplantation n=2 Participants Recipients will receive a conditioning regimen that starts with Rituximab on day -7 (and days -2, 5, 12), Whole Body Irradiation 1.5 Gy x2 on study days -6 and -5, followed by ATG on Days -2, -1, 0. Belatacept 10mg/kg on Days 0, 3, 10, 17, 24, 38, 52. Thymic irradiation (7 Gy) will be given on study day -1, and combined renal and bone marrow transplant will be done on study day 0. Prednisone will be started at 2 mg/kg on day 4 and tapered off by day 20. Tacrolimus will be administered on study days -1 through 60, and then tapered if weaning criteria are met. Belatacept: A selective T-cell (lymphocyte) costimulation blocker ATG: A T-Cell Depleting Agent Rituximab: B-Cell Depleting Agent Total Body Irradiation Thymic Irradiation Combined Bone Marrow/Kidney Transplantation
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	37 years STANDARD_DEVIATION 5.5 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	2 participants n=5 Participants

PRIMARY outcome

Timeframe: 5 Years

Population: Two subjects underwent conditioning regimen

The Primary Outcome is: The induction of transient mixed chimerism and renal allograft tolerance (24 consecutive months off of immunosuppression)

Outcome measures

Measure

Combined Bone Marrow and Kidney Transplantation n=2 Participants Recipients will receive a conditioning regimen that starts with Rituximab on day -7 (and days -2, 5, 12), Whole Body Irradiation 1.5 Gy x2 on study days -6 and -5, followed by ATG on Days -2, -1, 0. Belatacept 10mg/kg on Days 0, 3, 10, 17, 24, 38, 52. Thymic irradiation (7 Gy) will be given on study day -1, and combined renal and bone marrow transplant will be done on study day 0. Prednisone will be started at 2 mg/kg on day 4 and tapered off by day 20. Tacrolimus will be administered on study days -1 through 60, and then tapered if weaning criteria are met. Belatacept: A selective T-cell (lymphocyte) costimulation blocker ATG: A T-Cell Depleting Agent Rituximab: B-Cell Depleting Agent Total Body Irradiation Thymic Irradiation Combined Bone Marrow/Kidney Transplantation

Number of Participants With Successful Withdrawal of Immunosuppression

2 Participants

Adverse Events

Combined Bone Marrow and Kidney Transplantation

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure

Combined Bone Marrow and Kidney Transplantation n=2 participants at risk Recipients will receive a conditioning regimen that starts with Rituximab on day -7 (and days -2, 5, 12), Whole Body Irradiation 1.5 Gy x2 on study days -6 and -5, followed by ATG on Days -2, -1, 0. Belatacept 10mg/kg on Days 0, 3, 10, 17, 24, 38, 52. Thymic irradiation (7 Gy) will be given on study day -1, and combined renal and bone marrow transplant will be done on study day 0. Prednisone will be started at 2 mg/kg on day 4 and tapered off by day 20. Tacrolimus will be administered on study days -1 through 60, and then tapered if weaning criteria are met. Belatacept: A selective T-cell (lymphocyte) costimulation blocker ATG: A T-Cell Depleting Agent Rituximab: B-Cell Depleting Agent Total Body Irradiation Thymic Irradiation Combined Bone Marrow/Kidney Transplantation

Renal and urinary disorders Thrombotic Microangiopathy

50.0% 1/2 • Number of events 1 • 5 years An adverse event is any occurrence or worsening of an undesirable or unintended sign, symptom, laboratory finding, or disease that occurs during participation in the trial. An adverse event will be followed until it resolves or until 30 days after a participant terminates from the study, whichever comes first.

Other adverse events

Measure	Combined Bone Marrow and Kidney Transplantation n=2 participants at risk Recipients will receive a conditioning regimen that starts with Rituximab on day -7 (and days -2, 5, 12), Whole Body Irradiation 1.5 Gy x2 on study days -6 and -5, followed by ATG on Days -2, -1, 0. Belatacept 10mg/kg on Days 0, 3, 10, 17, 24, 38, 52. Thymic irradiation (7 Gy) will be given on study day -1, and combined renal and bone marrow transplant will be done on study day 0. Prednisone will be started at 2 mg/kg on day 4 and tapered off by day 20. Tacrolimus will be administered on study days -1 through 60, and then tapered if weaning criteria are met. Belatacept: A selective T-cell (lymphocyte) costimulation blocker ATG: A T-Cell Depleting Agent Rituximab: B-Cell Depleting Agent Total Body Irradiation Thymic Irradiation Combined Bone Marrow/Kidney Transplantation
Skin and subcutaneous tissue disorders HSV Lesion	50.0% 1/2 • Number of events 1 • 5 years An adverse event is any occurrence or worsening of an undesirable or unintended sign, symptom, laboratory finding, or disease that occurs during participation in the trial. An adverse event will be followed until it resolves or until 30 days after a participant terminates from the study, whichever comes first.
Immune system disorders Neutropenia	50.0% 1/2 • Number of events 1 • 5 years An adverse event is any occurrence or worsening of an undesirable or unintended sign, symptom, laboratory finding, or disease that occurs during participation in the trial. An adverse event will be followed until it resolves or until 30 days after a participant terminates from the study, whichever comes first.
Musculoskeletal and connective tissue disorders Heel pain	50.0% 1/2 • Number of events 1 • 5 years An adverse event is any occurrence or worsening of an undesirable or unintended sign, symptom, laboratory finding, or disease that occurs during participation in the trial. An adverse event will be followed until it resolves or until 30 days after a participant terminates from the study, whichever comes first.

Additional Information

Tatsuo Kawai, MD PhD

Massachusetts General Hospital

Phone: 617-726-0289

Email: tkawai@mgh.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place