Abatacept for Graft-versus-Host Disease Prevention

(ASCENT Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called abatacept (Orencia) to determine its effectiveness in preventing graft-versus-host disease (GVHD) in children and teens receiving stem cell transplants from unrelated donors. GVHD occurs when transplanted cells attack the recipient's body. The trial combines abatacept with standard treatments to assess its ability to protect against GVHD without compromising the transplant's success or weakening the immune system. Children with serious blood disorders, such as sickle cell disease or thalassemia, undergoing these transplants may be suitable candidates. Participants will receive eight doses of abatacept and will be monitored over several years to evaluate the treatment's effectiveness and safety. As a Phase 2 trial, this research measures the treatment's efficacy in an initial, smaller group, allowing participants to contribute to significant medical advancements.

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.

Is there any evidence suggesting that abatacept is likely to be safe for humans?

Research has shown that abatacept is generally safe for people. The FDA has already approved it to help prevent acute graft-versus-host disease (GVHD), a serious condition that can occur after a transplant. In other studies, about 10% of people reported side effects such as low red blood cell count (anemia), high blood pressure, and some viral infections. However, these side effects are common with similar treatments. Abatacept effectively prevents GVHD. While the treatment is usually well-tolerated, awareness of these possible side effects is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Abatacept is unique because it offers a novel approach to preventing graft-versus-host disease (GVHD), a serious complication after stem cell transplants. Unlike current standard treatments that primarily suppress the immune system broadly, abatacept specifically targets the interaction between certain immune cells, potentially reducing GVHD with fewer side effects. Researchers are excited because abatacept may improve outcomes for pediatric patients by providing more precise immune regulation, which could lead to better recovery and fewer complications compared to traditional methods.

What evidence suggests that abatacept might be an effective treatment for preventing graft-versus-host disease?

Research has shown that abatacept, which participants in this trial will receive, can help prevent graft-versus-host disease (GVHD), a serious complication after a stem cell transplant. One study found that patients who received abatacept along with other treatments had a 98% survival rate 180 days after their transplant, much higher than those who didn't receive abatacept. Another study found that survival rates with abatacept exceeded 95%, indicating its effectiveness in preventing GVHD. These findings suggest that abatacept can protect patients undergoing stem cell transplants from this serious issue. ^{1 2 3 6 7}

Who Is on the Research Team?

John Horan, MD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9943961/

Role of abatacept in the prevention of graft-versus-host disease Abatacept therapy was able to rescue immune function and led to an effective and safe clinical outcome. In an observational cohort study ...

2. ashpublications.org ashpublications.org/blood/article/144/17/1834/517112/Abatacept-for-acute-graft-versus-host-disease

Abatacept for acute graft-versus-host disease prophylaxis after ... Primary outcomes included day-180, 1-year, and 2-year overall survival (OS) and relapse-free survival (RFS) for abatacept + CNI/MTX vs CNI/MTX, ...

3. orenciahcp.com orenciahcp.com/graft-versus-host-disease.html

Prophylaxis of acute graft versus host disease (aGVHD) Of 116 patients who received ORENCIA, 7% (n=8) experienced CMV invasive diseases up to day 225 post-transplant. The median time to onset of the event was 91 ...

4. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-abatacept-prophylaxis-acute-graft-versus-host-disease

FDA approves abatacept for prophylaxis of acute graft The OS rate at Day 180 after HSCT was 98% (95% CI: 78%, 100%) for patients who received abatacept in combination with CNI and MTX compared to 75 ...

5. astctjournal.org astctjournal.org/article/S2666-6367(25)01257-6/fulltext

Impact of Abatacept Inclusive Graft-Versus-Host Disease ... Overall survival and event-free survival were 87% and 80% with prednisone. The corresponding numbers were 95% and 90%, respectively, with abatacept, despite a ...

6. ashpublications.org ashpublications.org/blood/article/142/8/680/497464/GVHD-better-safe-than-sorry

GVHD: better safe than sorry | American Society of Hematology Higher abatacept exposure decreases the occurrence of acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2666636725012576

Impact of Abatacept Inclusive Graft-Versus-Host Disease ... We hypothesized that adding abatacept to standard prophylaxis and extending the duration of treatment could safely decrease both acute and chronic GVHD (cGVHD) ...