Abatacept for Graft-versus-Host Disease Prevention

(ASCENT Trial)

Recruiting at 8 trial locations

Overseen By Elizabeth Stenger, MD, MSc

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Disqualifiers: HLA matched donor, Pulmonary dysfunction, Renal dysfunction, Severe cardiac dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 150 days

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial will see if extended abatacept administration (combined with a standard regimen of tacrolimus and mycophenolate mofetil) will prevent acute and chronic graft-versus-host disease (GVHD) in children and adolescents receiving unrelated donor (URD) hematopoietic stem cell transplantation (HSCT), without compromising their engraftment or reconstitution of protective immunity to infection. The study will enroll 30 pediatric patients with serious non-malignant hematologic diseases (NMHD) undergoing URD HSCT. The trial will include patients with 7/8 donors and those with 8/8 (matched) donors. All participants will receive 8 doses of abatacept. Recruitment is expected to last for about 2 years and participants will be followed for up to 3 years.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug abatacept for preventing graft-versus-host disease?

Research shows that abatacept, when used with other medications, is effective in preventing moderate to severe acute graft-versus-host disease in patients undergoing stem cell transplants. It has also shown promise in treating chronic cases where steroids are not effective, with studies reporting significant improvements and reduced steroid use. ^{1 2 3 4 5}

Is abatacept safe for humans?

Abatacept, also known as Orencia, has been tested in clinical trials for preventing graft-versus-host disease and was generally well-tolerated with no serious side effects reported. It has been used safely in patients with other conditions, showing promise as a treatment option. ^{1 2 3 5 6}

How is the drug abatacept unique in preventing graft-versus-host disease?

Abatacept is unique because it works by blocking T-cell activation, which helps prevent graft-versus-host disease (GvHD) after stem cell transplants. Unlike other treatments, it is used in combination with traditional drugs like calcineurin inhibitors and methotrexate, and has shown effectiveness in both acute and chronic GvHD, especially in cases where steroids are not effective. ^{1 2 3 6 7}

Research Team

John Horan, MD

Principal Investigator

Emory University

Eligibility Criteria

This trial is for children and adolescents with serious non-malignant hematologic diseases who are undergoing stem cell transplantation from an unrelated donor. Participants must be aged between 0-20.99 years, depending on their condition, and have a matched or nearly matched donor. They cannot join if they have certain organ dysfunctions, HIV, uncontrolled infections, recent clinical stroke, or are pregnant.

Inclusion Criteria

I have a diagnosed artery condition in my brain shown by specific tests.

I have had a stroke confirmed by brain scans showing damage.

I have a rare blood disorder or immune system condition.

Exclusion Criteria

My lung function is significantly reduced, below 40% of what is expected.

I do not have any ongoing serious infections.

I have not had a stroke in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Participants complete a conditioning regimen to prevent donor cell rejection

10-11 days

In-hospital stay

Treatment

Participants receive 8 doses of abatacept in addition to conventional GVHD prophylaxis

150 days

8 visits for abatacept administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Treatment Details

Interventions

• Abatacept

Trial Overview The study tests whether extended use of abatacept can prevent acute and chronic graft-versus-host disease in pediatric patients receiving stem cell transplants without affecting engraftment or immune reconstitution. All participants will receive eight doses of abatacept along with standard medications tacrolimus and mycophenolate mofetil.

Participant Groups

Group I: Participants Receiving Abatacept Experimental Treatment 1 Intervention

Pediatric participants who are undergoing URD HSCT for serious NMHD will receive 8 doses of abatacept in addition to conventional GVHD prophylaxis.

Abatacept is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis
• Psoriatic arthritis

Approved in United States as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis
• Psoriatic arthritis

Approved in Canada as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis

Approved in Japan as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Sickle Cell Transplant Advocacy & Research Alliance (STAR)

Collaborator

Trials

1

Recruited

30+

Aflac Cancer and Blood Disorders Center

Collaborator

Trials

1

Recruited

30+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Thrasher Research Fund

Collaborator

Trials

135

Recruited

96,600+

Findings from Research

Abatacept has been shown to effectively prevent moderate to severe acute graft-versus-host disease (GvHD) when used alongside traditional treatments in allogeneic hematopoietic stem cell transplants, particularly with unrelated donors.

Emerging evidence suggests that abatacept may also protect against chronic GvHD and can be beneficial in treating steroid-refractory cases, indicating its potential for broader applications in GvHD management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of abatacept in the prevention of graft-versus-host disease: current perspectives. Ngwube, A., Rangarajan, H., Shah, N.[2023]

In a phase 1 clinical trial involving 16 patients with steroid-refractory chronic graft-versus-host disease (SR-cGVHD), the immunomodulatory drug abatacept was found to be safe and well-tolerated, with no dose-limiting toxicities reported.

Abatacept led to a 44% clinical partial response rate and a significant 51.3% reduction in prednisone usage among responders, indicating its potential as an effective treatment option for SR-cGVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 clinical trial evaluating abatacept in patients with steroid-refractory chronic graft-versus-host disease. Nahas, MR., Soiffer, RJ., Kim, HT., et al.[2021]

In a phase 2 study involving 36 patients with steroid-refractory chronic graft-versus-host disease (cGVHD), abatacept demonstrated an overall response rate of 58%, with all responders achieving a partial response, indicating its efficacy as a treatment option.

Abatacept was well tolerated, showing few serious infections, and it positively impacted the immune system by reducing levels of inflammatory markers like IL-1α and TNF-α, suggesting it modifies the immune microenvironment in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 clinical trial evaluating abatacept in patients with steroid-refractory chronic graft-versus-host disease. Koshy, AG., Kim, HT., Liegel, J., et al.[2023]

In a study of 24 children with beta-thalassemia major undergoing stem cell transplants, adding abatacept to standard GVHD prophylaxis resulted in a significant reduction in severe acute GVHD incidence by day +100, with no cases of grades III-IV GVHD compared to 50% in the standard group.

The addition of abatacept did not affect engraftment rates and led to a higher thalassemia-free survival rate of 100% in the abatacept group versus 62.5% in the standard group, indicating its potential as a safe and effective enhancement to GVHD prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Graft-versus-host Disease Prophylaxis With Abatacept Reduces Severe Acute Graft-versus-host Disease in Allogeneic Hematopoietic Stem Cell Transplant for Beta-thalassemia Major With Busulfan, Fludarabine, and Thiotepa. Khandelwal, P., Yeh, RF., Yu, L., et al.[2021]

In a first-in-disease trial involving patients undergoing unrelated-donor hematopoietic cell transplantation, the addition of abatacept significantly inhibited the proliferation and activation of CD4(+) T cells, particularly the effector memory subpopulation, compared to a control group.

The use of abatacept resulted in a low incidence of acute graft-versus-host disease (aGVHD), with only 2 out of 10 patients developing grade II-IV aGVHD by day +100, and no related deaths or transplantation-related mortality, suggesting its potential as an effective adjunct therapy for aGVHD prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo T cell costimulation blockade with abatacept for acute graft-versus-host disease prevention: a first-in-disease trial. Koura, DT., Horan, JT., Langston, AA., et al.[2015]

References

1. England pubmed.ncbi.nlm.nih.gov

Role of abatacept in the prevention of graft-versus-host disease: current perspectives. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Phase 1 clinical trial evaluating abatacept in patients with steroid-refractory chronic graft-versus-host disease. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Phase 2 clinical trial evaluating abatacept in patients with steroid-refractory chronic graft-versus-host disease. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Graft-versus-host Disease Prophylaxis With Abatacept Reduces Severe Acute Graft-versus-host Disease in Allogeneic Hematopoietic Stem Cell Transplant for Beta-thalassemia Major With Busulfan, Fludarabine, and Thiotepa. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

In vivo T cell costimulation blockade with abatacept for acute graft-versus-host disease prevention: a first-in-disease trial. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Phase II Trial of Costimulation Blockade With Abatacept for Prevention of Acute GVHD. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Abatacept as salvage therapy in chronic graft-versus-host disease-a retrospective analysis. [2021]