Extended vs Short-Term Abatacept Dosing for Graft-versus-Host Disease

(ABA3 Trial)

Not currently recruiting at 15 trial locations

Overseen By Brandi M Bratrude, BA

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Boston Children's Hospital

Must be taking: Calcineurin inhibitors, Methotrexate

Disqualifiers: Chronic lymphocytic leukemia, Myeloma, Primary myelofibrosis, others

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: Unknown

Duration: 4-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests different schedules of the drug abatacept (Orencia) to determine which is more effective in preventing graft-versus-host disease (GVHD), a serious condition that can occur after a bone marrow transplant. One group will receive four doses, while the other will receive eight doses, with both groups also receiving standard treatments. The goal is to identify which dosing schedule helps patients remain healthy without severe GVHD or cancer recurrence. This trial targets individuals who have undergone a bone marrow transplant from a nearly matched donor and have a blood cancer in remission. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that abatacept is generally safe for individuals who have undergone transplants. In one study, only 7% of patients experienced issues with infections like CMV, a type of virus, up to about seven months post-transplant. Another study found that abatacept helped prevent serious conditions like PRES, a brain disorder, and reduced the risk of graft-versus-host disease, where the body attacks the transplanted cells.

The FDA has approved abatacept for preventing acute graft-versus-host disease in transplant patients. This approval indicates that abatacept is well-tolerated and safe for similar situations. Overall, these findings suggest abatacept is safe, with some manageable risks, for individuals considering its use in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for graft-versus-host disease (GVHD) because they explore different dosing schedules of Abatacept. Unlike the standard care, which typically involves calcineurin inhibitors like cyclosporine or tacrolimus paired with methotrexate, these treatments incorporate Abatacept, which works by modulating the immune response to reduce GVHD risk. The extended dosing arm offers an innovative approach by providing more doses of Abatacept, potentially enhancing its effectiveness and offering longer protection. This could lead to better outcomes and fewer complications for patients undergoing stem cell transplants.

What evidence suggests that this trial's treatments could be effective for graft-versus-host disease?

This trial will compare different dosing schedules of abatacept for graft-versus-host disease (GVHD). Research has shown that abatacept can help reduce GVHD, a common problem after transplants. One study found that patients who received abatacept experienced fewer cases of severe acute GVHD compared to those who did not. Participants in this trial may receive either a standard dosing schedule of abatacept with placebo or an extended dosing schedule of abatacept. Taking abatacept for a longer period has been shown to further lessen the severity of both acute and chronic GVHD. In studies with mice, abatacept successfully prevented graft rejection and GVHD. Overall, abatacept, especially with longer use, appears promising in improving transplant outcomes and reducing complications. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for patients at least 2 years old, weighing over 10 kg, with certain hematologic malignancies treatable by HCT and in remission. They need a partially matched unrelated donor and must not have severe psychiatric diseases, active infections, HIV, or inherited predispositions to cancer or transplant morbidities.

Inclusion Criteria

All patients and/or their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.

I am mostly able to carry out normal activities without assistance.

If the patient does not meet defined eligibility requirements, the PI/study committee must be contacted to determine eligibility.

Exclusion Criteria

Pregnancy (positive serum b-HCG) or breastfeeding.

Exclusion Criteria Prior to Randomization (prior to 5th dose of abatacept/placebo):

My MDS does not have more than 5% blasts.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 4 doses of abatacept on Days -1, +5, +14, +28, followed by randomization to either 4 additional doses of placebo or 4 more doses of abatacept

4-8 weeks

Follow-up

Participants are monitored for severe AGVHD-free, severe CGVHD-free, relapse-free survival (SGRFS) with a minimum follow-up of one year post-transplant

1 year

Long-term follow-up

Participants continue to be monitored for outcomes such as severe chronic GVHD, non-relapse mortality, and relapse-free survival until 2 years post-transplant

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Abatacept
• Placebo

Trial Overview The study compares extended versus short-term dosing of Abatacept added to standard GVHD prophylaxis in patients receiving transplants from mismatched donors. It aims to determine which regimen better prevents severe acute and chronic GVHD without relapse post-transplant.

How Is the Trial Designed?

Group I: Standard GVHD Prophylaxis + Abatacept Extended dosing Experimental Treatment 1 Intervention

Standard GVHD prophylaxis of calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate + 8 doses of Abatacept.

Group II: Standard GVHD Prophylaxis + Abatacept + Placebo Placebo Group 2 Interventions

Standard GVHD prophylaxis of calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate + 4 doses of Abatacept (investigational product) + 4 doses of Placebo.

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?

Boston Children's Hospital

Lead Sponsor

Trials

801

Recruited

5,584,000+

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

Published Research Related to This Trial

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 phase 1 trial involving 10 pediatric patients with nonmalignant diseases undergoing unrelated donor hematopoietic cell transplantation, the addition of abatacept (Aba) to standard GVHD prophylaxis was found to be safe and well-tolerated, with no severe acute or chronic graft-versus-host disease (GVHD) observed.

The trial showed promising preliminary efficacy, as 9 out of 10 patients successfully engrafted and 8 were off systemic immunosuppression after one year, indicating that Aba may help in preventing GVHD without negatively impacting immune reconstitution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abatacept GVHD prophylaxis in unrelated hematopoietic cell transplantation for pediatric bone marrow failure. Stenger, EO., Watkins, B., Rogowski, K., et al.[2023]

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 the ABA2 study, the T-cell costimulation blockade agent abatacept was found to be safe and effective in preventing acute graft-versus-host disease (aGVHD) after unrelated-donor hematopoietic cell transplant, leading to its FDA approval.

A higher trough concentration of abatacept (≥39 μg/mL) was associated with a significantly reduced risk of grade 2-4 aGVHD, while no safety concerns were linked to this higher concentration, indicating a favorable risk-benefit profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher abatacept exposure after transplant decreases acute GVHD risk without increasing adverse events. Takahashi, T., Al-Kofahi, M., Jaber, M., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04380740

Extended vs Short-term Abatacept Dosing for Graft Versus ... This is a multicenter randomized, double blind, Phase 2 trial for patients receiving transplants from 7 of 8 HLA matched donors, in which an extended dosing ...

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

Role of abatacept in the prevention of graft-versus-host disease Administration of abatacept following transplantation has been reported to inhibit graft rejection and graft-versus-host-disease (GvHD) in mouse models.

3. 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, ...

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

Impact of Abatacept Inclusive Graft-Versus-Host Disease ... Extended duration abatacept reduced the incidence and severity of acute and severity of chronic graft-versus-host disease (GVHD) after matched and ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/pbc.32085

Abatacept Prevents Severe Acute Graft‐Versus‐Host ... Results. None of the patients in the ABA cohort experienced severe (Grade III–IV) acute GVHD compared to 14% in our historical cohort (CI ...

6. 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 ...

7. ashpublications.org ashpublications.org/blood/article/142/8/700/496372/Higher-abatacept-exposure-after-transplant

Higher abatacept exposure after transplant decreases acute ... In the ABA2 study, the T-cell costimulation blockade agent, abatacept, was safe and effective in preventing acute graft-versus-host disease ( ...

8. 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 ...