Ibrutinib for Preventing Graft-versus-Host Disease

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Warfarin, Strong CYP3A inhibitors

Disqualifiers: Uncontrolled acute GVHD, Active infections, Stroke, 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

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: 1

Duration: 12 months

40 Participants Needed

Trial Summary

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

The trial protocol does not specify if you need to stop your current medications. However, you cannot take certain medications like strong CYP3A inhibitors or anticoagulants like warfarin while participating in the trial. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Ibrutinib for preventing graft-versus-host disease?

Ibrutinib has been shown to be effective in treating chronic graft-versus-host disease (cGVHD) in patients who did not respond to other treatments, with studies demonstrating high rates of sustained responses and manageable side effects. Additionally, research in mice has shown that Ibrutinib can significantly reduce the severity of cGVHD, suggesting its potential as a preventive treatment. ^{1 2 3 4 5}

Is ibrutinib safe for preventing graft-versus-host disease?

Ibrutinib has been approved for use in both adults and children with graft-versus-host disease, but it comes with warnings about potential risks like bleeding, infections, heart problems, and other side effects such as muscle pain, fever, and diarrhea. It's important for participants to be aware of these risks and discuss them with their healthcare provider. ^{1 3 4 6 7}

How does the drug ibrutinib differ from other treatments for preventing graft-versus-host disease?

Ibrutinib is unique because it targets both B cells and T cells by inhibiting Bruton's tyrosine kinase (BTK) and IL-2 inducible T cell kinase (ITK), which are crucial in the development of chronic graft-versus-host disease (cGVHD). This dual action helps prevent and treat cGVHD more effectively than treatments that do not target these pathways. ^{1 2 3 4 7}

What is the purpose of this trial?

This phase II trial tests how well ibrutinib works in preventing chronic graft-versus-host disease (GVHD) in patients undergoing donor (allogeneic) hematopoietic cell transplantation (HCT). An allogeneic hematopoietic cell transplantation (allo-HCT) is a treatment in which a person receives blood-forming stem cells (cells from which all blood cells develop) from a genetically similar, but not identical donor. When healthy stem cells from a donor are infused into a patient, they may help the patient's bone marrow make more healthy cells and platelets. However, sometimes the transplanted cells from a donor can attack the body's normal cells (called GVHD). Giving ibrutinib after the transplant may stop that from happening. Ibrutinib is in a class of medications called kinase inhibitors. It works by blocking a protein in the blood called Bruton's tyrosine kinase (BTK). By blocking BTK, ibrutinib inhibits certain immune cells that play a role in cGVHD. Giving ibrutinib after an allo-HCT may prevent the development of chronic GVHD.

Research Team

Mohamed A. Kharfan Dabaja, MD, MBA

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for patients who've had a donor stem cell transplant to treat conditions like cancer. It's designed to see if taking Ibrutinib after the transplant can prevent chronic graft-versus-host disease, which happens when donor cells attack the patient's body.

Inclusion Criteria

Provide written informed consent

Hemoglobin must be ≥ 8.0 g/dL (untransfused) (obtained ≤ 7 days prior to registration)

I had my transplant between 50 and 110 days ago.

Exclusion Criteria

Nursing persons

Active hepatitis B or C infection

Patients known to have tested positive on HIV antibody test

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive ibrutinib orally once daily on days 1-30 of each cycle. Cycles repeat every 30 days for up to 12 cycles.

12 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including the incidence of chronic GVHD and other outcomes.

12 months

Quarterly visits (in-person)

Treatment Details

Interventions

• Ibrutinib

Trial Overview The study is testing Ibrutinib, a kinase inhibitor that blocks proteins involved in immune responses that could lead to chronic GVHD. The goal is to determine if it can help prevent this condition post-transplant.

Participant Groups

Group I: Prevention (ibrutinib) Experimental Treatment 2 Interventions

Patients receive ibrutinib PO QD on days 1-30 of each cycle. Cycles repeat every 30 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo an echocardiography prior to registration on study.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Findings from Research

Ibrutinib (IMBRUVICA) was approved by the FDA for treating chronic graft versus host disease (cGVHD) after other treatments failed, based on a trial with 42 patients that included patient-reported outcomes (PRO) to support efficacy results.

In the trial, 18 patients showed a significant improvement in symptoms, with 10 maintaining this improvement over time, indicating that ibrutinib not only helps clinicians assess treatment effectiveness but also aligns with patients' experiences of symptom relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA review summary of patient-reported outcome results for ibrutinib in the treatment of chronic graft versus host disease. King-Kallimanis, BL., Wroblewski, T., Kwitkowski, V., et al.[2021]

Ibrutinib, an FDA-approved drug, shows promise in reversing established chronic graft-versus-host disease (cGVHD) in mouse models by improving survival and reducing disease symptoms, indicating its potential efficacy as a treatment.

The study highlights that both CD4+ T cells and B cells are crucial in the development of cGVHD, and ibrutinib's ability to inhibit these cells suggests it could be a valuable therapeutic option for patients with cGVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib treatment ameliorates murine chronic graft-versus-host disease. Dubovsky, JA., Flynn, R., Du, J., et al.[2021]

Ibrutinib, an FDA-approved inhibitor of BTK and ITK, significantly reduced chronic graft-versus-host disease (cGVHD) in four different mouse models, leading to improved long-term survival and lower clinical scores.

The treatment with Ibrutinib resulted in decreased levels of serum autoantibodies and reduced B-cell proliferation, indicating its potential as a safe and effective prophylactic strategy against cGVHD in patients undergoing allogeneic hematopoietic stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of BTK and ITK with Ibrutinib Is Effective in the Prevention of Chronic Graft-versus-Host Disease in Mice. Schutt, SD., Fu, J., Nguyen, H., et al.[2021]

In the phase III iNTEGRATE study involving 193 patients with chronic graft-versus-host disease (cGVHD), the combination of ibrutinib and prednisone did not show a statistically significant improvement in response rates compared to placebo plus prednisone after 48 weeks.

Both treatment groups experienced similar rates of serious adverse events (49% for ibrutinib-prednisone and 47% for placebo-prednisone), indicating that ibrutinib did not introduce new safety concerns in previously untreated cGVHD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib for First-Line Treatment of Chronic Graft-Versus-Host Disease: Results From the Randomized Phase III iNTEGRATE Study. Miklos, DB., Abu Zaid, M., Cooney, JP., et al.[2023]

Ibrutinib, approved by the FDA in 2017, shows high rates of sustained responses in patients with chronic graft-versus-host disease (cGvHD) who are steroid-refractory or -dependent, addressing a significant unmet need in this patient population.

The review discusses the mechanisms of action of ibrutinib and presents preclinical and clinical data that support its efficacy and manageable toxicity in treating cGvHD after failure of standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib for the treatment of patients with chronic graft-versus-host disease after failure of one or more lines of systemic therapy. Rahmat, LT., Logan, AC.[2021]

Ibrutinib (Imbruvica) is now approved for treating graft-versus-host disease in pediatric patients aged one year and older who have not responded to other systemic therapies, highlighting its efficacy in a challenging patient population.

The treatment carries significant risks, including severe side effects like hemorrhage, infections, and cardiac issues, necessitating careful monitoring and education for patients and caregivers about these potential adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Receives New Indication for Pediatric Graft-Versus-Host Disease. Aschenbrenner, DS.[2023]

Ibrutinib, a BTK inhibitor, is now approved in the USA for treating pediatric patients with chronic graft-versus-host disease (cGVHD) after they have failed one or more systemic therapies, making it the first treatment available for children under 12.

This approval expands the use of ibrutinib to a younger population, as it is already established for adults and adolescents with cGVHD, highlighting its efficacy in managing this condition across different age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: Pediatric First Approval. Keam, SJ.[2023]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

FDA review summary of patient-reported outcome results for ibrutinib in the treatment of chronic graft versus host disease. [2021]

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

Ibrutinib treatment ameliorates murine chronic graft-versus-host disease. [2021]

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

Inhibition of BTK and ITK with Ibrutinib Is Effective in the Prevention of Chronic Graft-versus-Host Disease in Mice. [2021]

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

Ibrutinib for First-Line Treatment of Chronic Graft-Versus-Host Disease: Results From the Randomized Phase III iNTEGRATE Study. [2023]

5. Spain pubmed.ncbi.nlm.nih.gov

Ibrutinib for the treatment of patients with chronic graft-versus-host disease after failure of one or more lines of systemic therapy. [2021]

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

Drug Receives New Indication for Pediatric Graft-Versus-Host Disease. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Ibrutinib: Pediatric First Approval. [2023]