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

Recruiting in Palo Alto (17 mi)

Overseen by Jaime Suarez Londono

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: NYU Langone Health

No Placebo Group

Prior Safety Data

Breakthrough Therapy

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.

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.

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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.

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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.

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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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

NYU Langone Health New York, NY

Who Is Running the Clinical Trial?

NYU Langone Health Lead Sponsor

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] Steroid-refractory chronic graft-versus-host disease (cGVHD) after allogeneic transplant remains a significant cause of morbidity and mortality. Abatacept is a selective costimulation modulator, used for the treatment of rheumatologic diseases, and was recently the first drug to be approved by the US Food and Drug Administration for the prophylaxis of acute graft-versus-host disease. We conducted a phase 2 study to evaluate the efficacy of abatacept in steroid-refractory cGVHD. The overall response rate was 58%, seen in 21 out of 36 patients, with all responders achieving a partial response. Abatacept was well tolerated with few serious infectious complications. Immune correlative studies showed a decrease in interleukin -1α (IL-1α), IL-21, and tumor necrosis factor α as well as decreased programmed cell death protein 1 expression by CD4+ T cells in all patients after treatment with abatacept, demonstrating the effect of this drug on the immune microenvironment. The results demonstrate that abatacept is a promising therapeutic strategy for the treatment of cGVHD. This trial was registered at www.clinicaltrials.gov as #NCT01954979.

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] The outcome of hyperacute grade 3-4 steroid-refractory graft-versus-host-disease (SR-GVHD) remains dismal despite a plethora of agents being tried alone or in combination. Following T replete haploidentical transplantation with post-transplantation cyclophosphamide on 75 patients, 10 patients (13%) aged 2-20years, developed hyperacute SR-GVHD. We report on the outcome of two different regimens for treatment of SR-GVHD on the outcome of these patients. Five patients were treated in Regimen A consisting of anti-thymocyte globulin, Etanercept and Basiliximab. The next 5 patients were treated combining T cell costimulation blockade with Abatacept along with Etanercept and Basiliximab. The overall response at days 29 and 56 were 40% and 0% with Regimen A and100% and 40% with Regimen B. The major cause of treatment failure was progression of GVHD and opportunistic infections. Two of the patients achieving a complete remission on Regimen B are long term disease free survivors off immunosuppression. Our study demonstrates the dismal outcome of early onset SR-GVHD in children following T replete haploidentical transplantation. However, the combination of Abatacept with anticytokine agents seems to produce encouraging early response and might warrant further investigation.

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] There is insufficient guidance in using posttransplant cyclophosphamide in patients with organ dysfunctions. Abatacept (Aba), a T cell costimulation blockade, has recently been shown to prevent severe acute graft-versus-host disease (GVHD).

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] Steroid-refractory chronic graft-versus-host disease (SR-cGVHD) remains a major cause of morbidity and mortality after allogeneic stem cell transplantation. Innovative immunotherapeutic strategies are urgently needed for the treatment of SR-cGVHD. We conducted a phase 1 clinical trial to evaluate the safety, efficacy, and immune effects of abatacept, a novel immunomodulatory drug that acts as an inhibitor of T-cell activation via costimulatory blockade, in the treatment of SR-cGVHD. The study followed a 3+3 design with 2 escalating abatacept doses: 3 mg/kg and 10 mg/kg, with an expansion cohort treated at 10 mg/kg. Abatacept was well-tolerated with no dose-limiting toxicities. Of the 16 evaluable patients, 44% achieved a clinical partial response per 2005 National Institutes of Health Consensus Criteria. Importantly, abatacept resulted in a 51.3% reduction in prednisone usage in clinical responders (mean baseline, 27 vs 14 mg; P = .01). Increased PD-1 expression on circulating CD4 (P = .009) and CD8 (P = .007) T cells was observed in clinical responders. In summary, abatacept was safe and led to a marked improvement in National Institutes of Health cGVHD scores and a significant reduction in prednisone use. In this cohort of heavily pretreated patients, the results suggest abatacept may be a promising therapeutic agent for SR-cGVHD, and a phase 2 trial has been initiated. This trial was registered at www.clinicaltrials.gov as #NCT01954979.

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] We performed a first-in-disease trial of in vivo CD28:CD80/86 costimulation blockade with abatacept for acute graft-versus-host disease (aGVHD) prevention during unrelated-donor hematopoietic cell transplantation (HCT). All patients received cyclosporine/methotrexate plus 4 doses of abatacept (10 mg/kg/dose) on days -1, +5, +14, +28 post-HCT. The feasibility of adding abatacept, its pharmacokinetics, pharmacodynamics, and its impact on aGVHD, infection, relapse, and transplantation-related mortality (TRM) were assessed. All patients received the planned abatacept doses, and no infusion reactions were noted. Compared with a cohort of patients not receiving abatacept (the StdRx cohort), patients enrolled in the study (the ABA cohort) demonstrated significant inhibition of early CD4(+) T cell proliferation and activation, affecting predominantly the effector memory (Tem) subpopulation, with 7- and 10-fold fewer proliferating and activated CD4(+) Tem cells, respectively, at day+28 in the ABA cohort compared with the StdRx cohort (P