What side effects are associated with this type of intervention?

The most common treatments for Graft-versus-Host Disease (GvHD) include Cyclophosphamide, Abatacept, and Tacrolimus. Cyclophosphamide can cause nausea, vomiting, hair loss, and increased infection risk. Abatacept may lead to headaches, dizziness, high blood pressure, and higher susceptibility to infections. Tacrolimus is associated with nephrotoxicity, neurotoxicity (such as tremors and headaches), hyperglycemia, hypertension, and an increased risk of infections. These side effects are critical to consider when using these agents for GvHD prophylaxis.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment and prophylaxis of Graft-versus-Host Disease (GvHD). Tacrolimus, a calcineurin inhibitor, is commonly used to suppress T-cell activation and proliferation. Cyclophosphamide, an alkylating agent, is used to eliminate alloreactive T cells. Abatacept, a fusion protein that inhibits T-cell activation, is also under investigation for GvHD prophylaxis. Other FDA-approved treatments include sirolimus, another calcineurin inhibitor, and mycophenolate mofetil, which inhibits T-cell and B-cell proliferation. These drugs are often used in combination to prevent and manage GvHD effectively.

What other types of research exist?

Promising novel alternatives for GvHD prophylaxis include: <ol> <li>Alemtuzumab: A monoclonal antibody targeting CD52 on T and B lymphocytes, showing efficacy in reducing GvHD.</li> <li></li> </ol> Ibrutinib: A Bruton's tyrosine kinase inhibitor, effective in B-cell malignancies and showing potential in GvHD management. 3. Venetoclax: A BCL-2 inhibitor, used in combination with other agents for its potential to reduce GvHD. 4. Idelalisib: A PI3K inhibitor, showing promise in B-cell malignancies and potential for GvHD prophylaxis.

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Alkylating agents

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

Phase 2

Recruiting

Led By Jaime Suarez Londono

Research Sponsored by NYU Langone Health

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to day 730

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include immune system suppression leading to increased infection risk, liver/kidney problems due to drug toxicity, potential for allergic reactions to medication components, and general discomfort like nausea or fatigue.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to day 730

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to day 730

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to day 730 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Cumulative Incidence of Grades II-IV Acute GvHD

Secondary study objectives

Cumulative Incidence of Chronic GvHD

GvHD and Relapse-Free Survival (GRFS) Rate

Number of Participants Presenting with Poor Graft Function

+5 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Reduced-Dose Post-Transplant Cyclophosphamide, Abatacept, and Short-Duration TacrolimusExperimental Treatment3 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cyclophosphamide

2010

Completed Phase 4

~2310

Abatacept

2005

Completed Phase 4

~112250

Tacrolimus

2019

Completed Phase 4

~5510

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Graft-versus-Host Disease (GvHD) include Cyclophosphamide, Abatacept, and Tacrolimus. Cyclophosphamide eliminates alloreactive T cells that attack the host's tissues. Abatacept inhibits T-cell activation by blocking necessary co-stimulatory signals. Tacrolimus suppresses T-cell activation and proliferation by inhibiting calcineurin, a protein essential for T-cell activation. These treatments are vital for GvHD patients as they help prevent donor immune cells from attacking the recipient's body, thereby reducing the incidence and severity of GvHD.

Successful treatment with reduced-intensity stem cell transplantation in a case of relapsed refractory central nervous system lymphoma.Sustained molecular remission in a patient with CML in blastic crisis receiving dose-reduced hematopoietic stem-cell transplantation followed by early withdrawal of cyclosporine and prophylactic use of interferon-alpha.