Trial Outcomes & Findings for Pilot of Abatacept-based Immunosuppression for Prevention of Acute GvHD During Unrelated Donor HCT (NCT NCT01012492)

Results Overview

Grade III-IV Acute GVHD by Day 100. The incidence of Gr III-IV acute GVHD was measured by the modified Glucksburg scale.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

11 participants

Primary outcome timeframe

Day 100 post-transplant

Results posted on

2019-11-21

Participant Flow

One patient signed consent but was determined to be an assignment failure prior to starting study activities.

Participant milestones

Participant milestones
Measure	Abatacept Participants will receive one of two standard myeloablative conditioning regimens for their stem cell transplant, and will receive an aGvHD prophylaxis regimen including cyclosporine, methotrexate, and abatacept. Abatacept: Participants will receive one of two standard myeloablative conditioning regimens for their stem cell transplant, and will receive an aGvHD prophylaxis regimen including cyclosporine, methotrexate, and abatacept.
Overall Study STARTED	10
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pilot of Abatacept-based Immunosuppression for Prevention of Acute GvHD During Unrelated Donor HCT

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Abatacept n=10 Participants Participants will receive one of two standard myeloablative conditioning regimens for their stem cell transplant, and will receive an aGvHD prophylaxis regimen including cyclosporine, methotrexate, and abatacept. Abatacept: Participants will receive one of two standard myeloablative conditioning regimens for their stem cell transplant, and will receive an aGvHD prophylaxis regimen including cyclosporine, methotrexate, and abatacept.
Age, Continuous	44.5 years STANDARD_DEVIATION 27 • n=93 Participants
Age, Categorical <=18 years	1 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=93 Participants
Age, Categorical >=65 years	1 Participants n=93 Participants
Sex: Female, Male Female	4 Participants n=93 Participants
Sex: Female, Male Male	6 Participants n=93 Participants
Region of Enrollment United States	10 participants n=93 Participants

PRIMARY outcome

Timeframe: Day 100 post-transplant

Grade III-IV Acute GVHD by Day 100. The incidence of Gr III-IV acute GVHD was measured by the modified Glucksburg scale.

Outcome measures

Outcome measures
Measure	Abatacept n=10 Participants Participants will receive one of two standard myeloablative conditioning regimens for their stem cell transplant, and will receive an aGvHD prophylaxis regimen including cyclosporine, methotrexate, and abatacept. Abatacept: Participants will receive one of two standard myeloablative conditioning regimens for their stem cell transplant, and will receive an aGvHD prophylaxis regimen including cyclosporine, methotrexate, and abatacept.
Percentage of Participants With Grade III-IV Acute GVHD by Day 100.	10 percentage of participants

SECONDARY outcome

Timeframe: 2 years after transplant

The rates of Grades III-IV acute GVHD were measured at 2 years according to standard Glucksberg criteria, which was 10%.

Outcome measures

Outcome measures
Measure	Abatacept n=10 Participants Participants will receive one of two standard myeloablative conditioning regimens for their stem cell transplant, and will receive an aGvHD prophylaxis regimen including cyclosporine, methotrexate, and abatacept. Abatacept: Participants will receive one of two standard myeloablative conditioning regimens for their stem cell transplant, and will receive an aGvHD prophylaxis regimen including cyclosporine, methotrexate, and abatacept.
Percentage of Participants With Grades III-IV Acute GVHD at 2 Years	10 percentage of participants

SECONDARY outcome

Timeframe: Day +100 post-transplant

Flow cytometric analysis of CD4 t-cell t-cell reconstitution was performed at day +100 post-transplant.

Outcome measures

Outcome measures
Measure	Abatacept n=10 Participants Participants will receive one of two standard myeloablative conditioning regimens for their stem cell transplant, and will receive an aGvHD prophylaxis regimen including cyclosporine, methotrexate, and abatacept. Abatacept: Participants will receive one of two standard myeloablative conditioning regimens for their stem cell transplant, and will receive an aGvHD prophylaxis regimen including cyclosporine, methotrexate, and abatacept.
Hematologic and Immunologic Reconstitution	285 cell per microlitre Standard Error 105

SECONDARY outcome

Timeframe: Day +365 post-transplant

Percent of CMV virus binding CD8+ t-cells at day +365 post-transplant

Outcome measures

Outcome measures
Measure	Abatacept n=10 Participants Participants will receive one of two standard myeloablative conditioning regimens for their stem cell transplant, and will receive an aGvHD prophylaxis regimen including cyclosporine, methotrexate, and abatacept. Abatacept: Participants will receive one of two standard myeloablative conditioning regimens for their stem cell transplant, and will receive an aGvHD prophylaxis regimen including cyclosporine, methotrexate, and abatacept.
Protective Immunity	2.8 percentage of total CD8+ t-cells Standard Error 1.7

Adverse Events

Abatacept

Serious events: 7 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Abatacept n=10 participants at risk In this trial, we will test the safety and tolerability of the addition of the CD28-B7 blockade agent, abatacept, as an adjunctive therapy for the prevention of GvHD in a high-risk BMT cohort. Four doses of abatacept will be given according to a dosing schedule based on previous trials using CD28-B7 blockade with belatacept in kidney transplantation. Pharmacokinetic and pharmakodynamic analysis of abatacept will be undertaken, as well as an evaluation of the incidence and severity of acute GvHD in this patient cohort. Dosage: Abatacept is administered as an intravenous infusion under medically controlled conditions. Dose is 10mg/kg with a maximum dose of 1 gram. Abatacept should be administered as a 30-minute intravenous infusion. In this study, abatacept will be dosed on days -1, +5, +14, +28 post-transplant. Small adjustments in dose to accommodate abatacept vial size may be acceptable. These dose adjustments must be approved by the study PI.
Blood and lymphatic system disorders Febrile neutropenia	40.0% 4/10 • Number of events 4 • One year post-transplant. Attribution of adverse events when patients are co-enrolled on other trials: because abatacept's effects are strictly immunologic and because co-enrollment will only be allowed in trials testing agents without immunomodulatory effects, all adverse events stemming directly or indirectly from immune deficiency or immune dysregulation will be attributed (definite, probable or possible depending on the circumstances) to abatacept and not the agent being tested in the other trial.
Infections and infestations Bacteremia with coagulase negative staphylococcus	10.0% 1/10 • Number of events 2 • One year post-transplant. Attribution of adverse events when patients are co-enrolled on other trials: because abatacept's effects are strictly immunologic and because co-enrollment will only be allowed in trials testing agents without immunomodulatory effects, all adverse events stemming directly or indirectly from immune deficiency or immune dysregulation will be attributed (definite, probable or possible depending on the circumstances) to abatacept and not the agent being tested in the other trial.
Infections and infestations Upper Respiratory Infection - Parainfluenza	10.0% 1/10 • Number of events 1 • One year post-transplant. Attribution of adverse events when patients are co-enrolled on other trials: because abatacept's effects are strictly immunologic and because co-enrollment will only be allowed in trials testing agents without immunomodulatory effects, all adverse events stemming directly or indirectly from immune deficiency or immune dysregulation will be attributed (definite, probable or possible depending on the circumstances) to abatacept and not the agent being tested in the other trial.
Infections and infestations Bacteremia with E. coli	10.0% 1/10 • Number of events 1 • One year post-transplant. Attribution of adverse events when patients are co-enrolled on other trials: because abatacept's effects are strictly immunologic and because co-enrollment will only be allowed in trials testing agents without immunomodulatory effects, all adverse events stemming directly or indirectly from immune deficiency or immune dysregulation will be attributed (definite, probable or possible depending on the circumstances) to abatacept and not the agent being tested in the other trial.
Infections and infestations Upper Respiratory Infection - Rhinovirus	10.0% 1/10 • Number of events 1 • One year post-transplant. Attribution of adverse events when patients are co-enrolled on other trials: because abatacept's effects are strictly immunologic and because co-enrollment will only be allowed in trials testing agents without immunomodulatory effects, all adverse events stemming directly or indirectly from immune deficiency or immune dysregulation will be attributed (definite, probable or possible depending on the circumstances) to abatacept and not the agent being tested in the other trial.
Infections and infestations Perianal cellulitis	10.0% 1/10 • Number of events 1 • One year post-transplant. Attribution of adverse events when patients are co-enrolled on other trials: because abatacept's effects are strictly immunologic and because co-enrollment will only be allowed in trials testing agents without immunomodulatory effects, all adverse events stemming directly or indirectly from immune deficiency or immune dysregulation will be attributed (definite, probable or possible depending on the circumstances) to abatacept and not the agent being tested in the other trial.
Infections and infestations Hemorrhagic cystitis with BK virus	10.0% 1/10 • Number of events 1 • One year post-transplant. Attribution of adverse events when patients are co-enrolled on other trials: because abatacept's effects are strictly immunologic and because co-enrollment will only be allowed in trials testing agents without immunomodulatory effects, all adverse events stemming directly or indirectly from immune deficiency or immune dysregulation will be attributed (definite, probable or possible depending on the circumstances) to abatacept and not the agent being tested in the other trial.
Blood and lymphatic system disorders Polyclonal lymphoproliferative disorder	10.0% 1/10 • Number of events 1 • One year post-transplant. Attribution of adverse events when patients are co-enrolled on other trials: because abatacept's effects are strictly immunologic and because co-enrollment will only be allowed in trials testing agents without immunomodulatory effects, all adverse events stemming directly or indirectly from immune deficiency or immune dysregulation will be attributed (definite, probable or possible depending on the circumstances) to abatacept and not the agent being tested in the other trial.

Other adverse events

Other adverse events
Measure	Abatacept n=10 participants at risk In this trial, we will test the safety and tolerability of the addition of the CD28-B7 blockade agent, abatacept, as an adjunctive therapy for the prevention of GvHD in a high-risk BMT cohort. Four doses of abatacept will be given according to a dosing schedule based on previous trials using CD28-B7 blockade with belatacept in kidney transplantation. Pharmacokinetic and pharmakodynamic analysis of abatacept will be undertaken, as well as an evaluation of the incidence and severity of acute GvHD in this patient cohort. Dosage: Abatacept is administered as an intravenous infusion under medically controlled conditions. Dose is 10mg/kg with a maximum dose of 1 gram. Abatacept should be administered as a 30-minute intravenous infusion. In this study, abatacept will be dosed on days -1, +5, +14, +28 post-transplant. Small adjustments in dose to accommodate abatacept vial size may be acceptable. These dose adjustments must be approved by the study PI.
Renal and urinary disorders Renal toxicity	40.0% 4/10 • Number of events 4 • One year post-transplant. Attribution of adverse events when patients are co-enrolled on other trials: because abatacept's effects are strictly immunologic and because co-enrollment will only be allowed in trials testing agents without immunomodulatory effects, all adverse events stemming directly or indirectly from immune deficiency or immune dysregulation will be attributed (definite, probable or possible depending on the circumstances) to abatacept and not the agent being tested in the other trial.
Gastrointestinal disorders Mucositis oral	50.0% 5/10 • Number of events 5 • One year post-transplant. Attribution of adverse events when patients are co-enrolled on other trials: because abatacept's effects are strictly immunologic and because co-enrollment will only be allowed in trials testing agents without immunomodulatory effects, all adverse events stemming directly or indirectly from immune deficiency or immune dysregulation will be attributed (definite, probable or possible depending on the circumstances) to abatacept and not the agent being tested in the other trial.
Infections and infestations Bladder toxicity	10.0% 1/10 • Number of events 1 • One year post-transplant. Attribution of adverse events when patients are co-enrolled on other trials: because abatacept's effects are strictly immunologic and because co-enrollment will only be allowed in trials testing agents without immunomodulatory effects, all adverse events stemming directly or indirectly from immune deficiency or immune dysregulation will be attributed (definite, probable or possible depending on the circumstances) to abatacept and not the agent being tested in the other trial.

Additional Information

Leslie S Kean

Emory University School of Medicine

Phone: 404-376-0187

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place