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

27 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial involves treating adults with blood cancers using less intense chemotherapy, followed by a stem cell transplant from a family member. Medications are given to prevent complications where the new cells might attack the patient's body.

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.

What data supports the idea that Cyclophosphamide + Abatacept + Tacrolimus for Graft-versus-Host Disease is an effective treatment?

The available research shows that using Abatacept, a part of the Cyclophosphamide + Abatacept + Tacrolimus combination, has shown promising results in treating Graft-versus-Host Disease. In one study, a combination treatment including Abatacept led to a 100% response rate at day 29 for patients with severe cases, compared to a 40% response rate with another treatment. Another study found that Abatacept alone had a 58% response rate in patients with chronic Graft-versus-Host Disease, showing it can be effective. These results suggest that the combination treatment could be a promising option for this condition. ^{1 2 3 4 5}

What data supports the effectiveness of the drug combination Cyclophosphamide, Abatacept, and Tacrolimus for treating graft-versus-host disease?

Research shows that Abatacept, one of the drugs in the combination, has been effective in treating steroid-refractory chronic graft-versus-host disease (cGVHD), with a 58% response rate in a phase 2 trial. Additionally, Abatacept has shown promise in preventing severe acute GVHD, suggesting it could be beneficial in combination with other drugs for this condition. ^{1 2 3 4 5}

What safety data exists for the treatment of Cyclophosphamide, Abatacept, and Tacrolimus in Graft-versus-Host Disease?

The safety data for Abatacept, a component of the treatment, shows it is well-tolerated in patients with steroid-refractory chronic graft-versus-host disease (SR-cGVHD) and acute graft-versus-host disease (aGVHD). In a Phase 1 trial, Abatacept was administered without dose-limiting toxicities, and in a Phase 2 trial, it was well-tolerated with few serious infectious complications. Additionally, in trials for aGVHD prevention, Abatacept was administered without infusion reactions and showed significant inhibition of T cell proliferation and activation. The combination of Abatacept with other agents in children with hyperacute SR-GVHD also showed encouraging early responses. However, specific safety data for the combination of Cyclophosphamide, Abatacept, and Tacrolimus is not detailed in the provided research. ^{1 2 3 4 5}

Is the combination of Cyclophosphamide, Abatacept, and Tacrolimus safe for treating Graft-versus-Host Disease?

Abatacept has been shown to be generally safe in humans, with studies indicating it is well-tolerated and has few serious side effects when used for Graft-versus-Host Disease. Cyclophosphamide and Tacrolimus are also commonly used in medical treatments, but specific safety data for this exact combination is not provided in the available research. ^{1 2 3 4 5}

Is the drug Cyclophosphamide, Tacrolimus a promising treatment for Graft-versus-Host Disease?

Yes, the drug Cyclophosphamide, Tacrolimus, when combined with Abatacept, shows promise in treating Graft-versus-Host Disease. Studies have shown that Abatacept, which is part of this combination, can effectively prevent and treat this condition, leading to positive responses in patients. ^{1 2 3 4 5}

How is the drug combination of Cyclophosphamide, Abatacept, and Tacrolimus unique for treating graft-versus-host disease?

This drug combination is unique because it includes Abatacept, which blocks T cell activation, potentially reducing the severity of graft-versus-host disease. Abatacept has shown promise in improving outcomes for patients who do not respond to standard steroid treatments, making it a novel option for those with difficult-to-treat cases. ^{1 2 3 4 5}

Research Team

Mohammad Maher Abdul Hay

Principal Investigator

NYU Langone Health

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

References

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

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

2. Netherlands pubmed.ncbi.nlm.nih.gov

T cell costimulation blockade for hyperacute steroid refractory graft versus-host disease in children undergoing haploidentical transplantation. [2018]

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

Abatacept-based Graft-Versus-Host Disease Prophylaxis in Haplo-identical Hematopoietic Cell Transplant in a High-risk Cohort. [2022]

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

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