Cyclophosphamide + Abatacept + Tacrolimus for Graft-versus-Host Disease

Overseen By Kelsey Stocker, AGPCNP, MSN, BS, RN, OCN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NYU Langone Health

Disqualifiers: Pregnancy, Heart failure, Psychiatric illness, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments to prevent graft-versus-host disease (GvHD), a condition where donor cells attack the recipient's body after a stem cell transplant. The trial tests a mix of cyclophosphamide (a chemotherapy drug), abatacept (also known as Orencia, an immunosuppressant), and tacrolimus (an immunosuppressant), administered in specific doses post-transplant. It targets adults with blood cancers receiving a stem cell transplant from a family member. Participants must show no signs of active infections and be in good overall health to join. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, since it involves specific treatments, it's best to discuss your current medications with the trial team.

Do I need to stop my current medications to join the trial?

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 this trial's treatments are likely to be safe?

A previous study showed that the combination of abatacept, cyclophosphamide, and tacrolimus holds promise for people undergoing stem cell transplants. Research indicates that this treatment mix can reduce the risk of developing serious chronic graft-versus-host disease (GvHD), a condition where the donor's immune cells attack the patient's body.

Abatacept and cyclophosphamide are already approved to help prevent GvHD, demonstrating a track record of safety for this purpose. The treatment is well-tolerated, meaning most people don't experience severe side effects. However, individual reactions vary, so side effects like nausea or fatigue might still occur.

Overall, existing data suggest this treatment is generally safe for humans. As with any medical treatment, it's essential to be aware of potential risks and discuss them with healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Cyclophosphamide, Abatacept, and Tacrolimus together for Graft-versus-Host Disease (GvHD) because this combination aims to improve patient outcomes by addressing the disease in a novel way. Unlike the standard treatments, which typically involve prolonged immunosuppression, this regimen uses a reduced dose of Cyclophosphamide and shorter Tacrolimus duration, potentially minimizing side effects. Additionally, Abatacept, which is not commonly used for GvHD, works by blocking a specific pathway in the immune system, offering a new mechanism of action. These features could mean more effective management of GvHD with fewer complications for patients.

What evidence suggests that this treatment might be an effective treatment for GvHD?

In this trial, participants will receive a combination of three drugs—cyclophosphamide, abatacept, and tacrolimus—to evaluate their effectiveness in preventing graft-versus-host disease (GVHD). Research has shown that this treatment mix results in less severe GVHD compared to some standard treatments. It also appears to reduce long-term GVHD and improve overall outcomes without causing more severe side effects. In trials, using these drugs together helped patients experience fewer problems after a transplant. This evidence supports the idea that these medications can effectively protect patients from GVHD. ^{3 6 7 8 9}

Who Is on the Research Team?

Mohammad Maher Abdul Hay

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

Adults with blood cancers needing a stem cell transplant from a relative can join if they're over 18, infection-free, have good kidney/liver/heart function, and are generally fit (Karnofsky score ≥ 70%). Women must not be pregnant and agree to contraception. Men must also use contraception. No recent heart attacks or severe heart disease allowed.

Inclusion Criteria

I do not have any worsening infections.

Alkaline phosphatase ≤ 250 IU/L

Left Ventricular Ejection Fraction (LVEF) > 45%

Exclusion Criteria

I am a male willing to use contraception or abstain from sex for the study duration and 90 days after.

I have specific antibodies against the donor's tissue.

Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning and Transplantation

Participants receive a conditioning regimen followed by peripheral blood hematopoietic stem cell transplantation

1 week

Inpatient stay for transplantation

Treatment

Participants receive reduced-dose cyclophosphamide, abatacept, and short-duration tacrolimus for GvHD prophylaxis

8 weeks

Multiple visits for drug administration and monitoring

Follow-up

Participants are monitored for safety, effectiveness, and incidence of GvHD

Up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Abatacept
• Cyclophosphamide
• Tacrolimus

Trial Overview This phase II trial tests Cyclophosphamide, Abatacept, and Tacrolimus in preventing Graft-versus-Host Disease after stem cell transplants from half-matched donors. It's an open-label study where all participants receive the same drugs following their transplant.

How Is the Trial Designed?

Group I: Reduced-Dose Post-Transplant Cyclophosphamide, Abatacept, and Short-Duration Tacrolimus Experimental Treatment 3 Interventions

Participants to receive: * Cyclophosphamide 25 mg/kg IV over 1 hour on Day 3 and Day 4 following transplant * Abatacept 10 mg/kg IV on Day 5, Day 14, Day 28, and Day 56 following transplant * Tacrolimus 0.02 mg/kg IV by continuous infusion, starting on Day 5 following transplant. May switch to oral administration when tolerated, adjusted to maintain a drug level between 5-12ng/mL. Tacrolimus treatment is continued until Day 60 and then tapered over a period of 4 weeks in the absence of GvHD.

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

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Published Research Related to This Trial

In a case report involving 4 pediatric patients undergoing haplo-hematopoietic cell transplantation, the addition of abatacept (Aba) for graft-versus-host disease (GVHD) prophylaxis resulted in reliable engraftment and acceptable levels of GVHD, even in patients with organ dysfunction.

All 4 patients remained alive with full donor chimerism, and 3 of them were able to discontinue immunosuppressants, suggesting that an Aba-based regimen can be a safe and effective alternative when traditional posttransplant cyclophosphamide is not feasible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abatacept-based Graft-Versus-Host Disease Prophylaxis in Haplo-identical Hematopoietic Cell Transplant in a High-risk Cohort. Raffa, EH., Srinivasan, A., Wall, DA., et al.[2022]

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 75 patients aged 2-20 years who underwent T replete haploidentical transplantation, 13% developed hyperacute steroid-refractory graft-versus-host disease (SR-GVHD), highlighting the serious challenges in treating this condition.

The treatment regimen combining Abatacept with anti-cytokine agents showed promising results, achieving a 100% response rate at day 29 and leading to long-term disease-free survival in two patients, suggesting this approach may be worth further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T cell costimulation blockade for hyperacute steroid refractory graft versus-host disease in children undergoing haploidentical transplantation. Jaiswal, SR., Zaman, S., Chakrabarti, A., et al.[2018]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40554429/

A prospective clinical trial of GVHD prophylaxis with ... We conducted a prospective randomized clinical trial to investigate the combination of posttransplant cyclophosphamide (PTCy) and abatacept (Aba) ...

2. ashpublications.org ashpublications.org/bloodadvances/article/9/16/4336/537897/A-prospective-clinical-trial-of-GVHD-prophylaxis

A prospective clinical trial of GVHD prophylaxis with ... In the ABA2 trial, patients who received abatacept (Aba) in addition to methotrexate and tacrolimus had less acute GVHD and improved severe- ...

3. hematologyadvisor.com hematologyadvisor.com/news/cyclophosphamide-abatecept-graft-host-disease-gvhd-treatment-risk/

Posttransplant Cyclophosphamide Plus Abatacept ... PTCy and abatacept significantly reduced chronic GVHD and improved GRFS compared with standard tacrolimus and methotrexate prophylaxis in ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11701941/

CAST Regimen for GvHD Prophylaxis: A CIBMTR Propensity ... Previously, we reported excellent results with the combination of post-transplant cyclophosphamide (PTCy), abatacept and a short course of tacrolimus (CAST) ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06859424

Study Details | NCT06859424 | A Platform Protocol to ... This platform protocol will evaluate the safety and efficacy of post-transplant cyclophosphamide (PTCy) based graft-versus-host disease (GVHD) prophylaxis after ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4905/533491/Abatacept-and-Post-Transplant-Cyclophosphamide

Abatacept and Post Transplant Cyclophosphamide Based ... The combination of Abatacept (ABA) with tacrolimus and methotrexate is FDA-approved for the prevention of acute graft versus host disease in ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124076638

Abatacept and Post Transplant Cyclophosphamide Based ... The combination of Abatacept (ABA) with tacrolimus and methotrexate is FDA-approved for the prevention of acute graft versus host disease in patients undergoing ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12402362/

A prospective clinical trial of GVHD prophylaxis with ... PTCy+Aba arm is associated with less chronic GVHD and a favorable GRFS compared with methotrexate/tacrolimus. PTCy and Aba without a calcineurin inhibitor ...

9. targetedonc.com targetedonc.com/view/posttransplant-cyclophosphamide-abatecept-reduces-moderate-severe-gvhd-compared-with-soc

Posttransplant Cyclophosphamide/Abatacept Reduces ... PTCy+Aba regimen significantly reduced moderate and severe chronic GVHD compared to SOC in HSCT patients, with a 0% rate versus 65.8% in the SOC ...