Ibrutinib for Chronic Graft-versus-Host Disease

Recruiting at 2 trial locations

Overseen By Steven Z Pavletic, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Immunosuppressive medications

Must not be taking: Ibrutinib, Rituximab

Disqualifiers: Malignant disease, Cardiac issues, Infections, 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: 3

Duration: 24 months

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing ibrutinib, a pill that blocks a protein causing harmful immune reactions, in adults with newly diagnosed moderate or severe chronic graft-versus-host disease (cGVHD). The goal is to see if this drug can help control the disease by reducing the immune system's attack on the body. Ibrutinib was the first agent approved by the U.S. Food and Drug Administration for the treatment of chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy.

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

The trial does not require you to stop your current medications, but your doses of other immunosuppressive drugs should be stable for at least 2 weeks before starting the study. You should discuss your specific medications with the trial team to ensure they are compatible with the study requirements.

What data supports the effectiveness of the drug ibrutinib for chronic graft-versus-host disease?

Ibrutinib has been shown to help patients with chronic graft-versus-host disease (cGVHD) who did not respond to other treatments, with studies showing it can improve symptoms and survival. It works by targeting specific cells involved in cGVHD, and has been approved by the FDA for this use based on clinical trial results. ^{1 2 3 4 5}

Is ibrutinib safe for treating chronic graft-versus-host disease?

Ibrutinib, also known as Imbruvica, is generally considered safe for treating chronic graft-versus-host disease, but it can have side effects. Common side effects include muscle pain, fever, pneumonia, stomach pain, mouth sores, diarrhea, and headaches. There are also warnings about more serious risks like bleeding, infections, heart problems, and high blood pressure. ^{1 2 5 6 7}

How is the drug ibrutinib unique in treating chronic graft-versus-host disease?

Ibrutinib is unique because it is the first drug approved for treating chronic graft-versus-host disease (cGVHD) in both adults and children after other treatments have failed. It works by inhibiting Bruton's tyrosine kinase (BTK), which is different from the standard first-line treatment of high-dose corticosteroids. ^{1 2 4 5 8}

Research Team

Steven Z Pavletic, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults over 18 with newly diagnosed moderate or severe chronic Graft-versus-Host Disease after a stem cell or bone marrow transplant can join. They must be responding to current treatments, agree to use birth control, and have no uncontrolled infections, bleeding disorders, other cancers (with some exceptions), heart issues, hepatitis B/C, or known allergy to Ibrutinib.

Inclusion Criteria

I have had a stem cell transplant from a donor.

I have been newly diagnosed with moderate or severe chronic GvHD and need systemic immunosuppression.

Your test results must be within certain ranges.

Exclusion Criteria

I do not have any uncontrolled infections or bleeding disorders.

My cancer has returned or worsened.

The researchers can decide not to include you for other reasons and they will write it down in your medical record.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive ibrutinib daily for up to 2 years, with regular monitoring and assessments

24 months

Every 2 weeks for the first 2 months, then every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with annual check-ins for 2 years

24 months

Annual contact

Treatment Details

Interventions

• Ibrutinib

Trial Overview The trial is testing if Ibrutinib can help as a first-line treatment for cGVHD without needing steroids. Participants will take the drug daily for up to two years and attend regular check-ups including physical exams and lung function tests while keeping a medicine diary.

Participant Groups

Group I: Ibrutinib Without Corticosteroids Experimental Treatment 16 Interventions

Determine response rate via continuous daily dose by mouth to determine efficacy

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

Approved in European Union as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in United States as Imbruvica for:

• Chronic lymphocytic leukemia/small lymphocytic lymphoma
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in Canada as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma

Approved in Japan as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

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]

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, 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, 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, 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]

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]

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

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

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

4. 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]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Ibrutinib: Pediatric First Approval. [2023]

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

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

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

Ibrutinib Treatment of Pediatric Chronic Graft-versus-Host Disease: Primary Results from the Phase 1/2 iMAGINE Study. [2022]

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

An Open-Label, Single-Arm, Multicenter Study of Ibrutinib in Japanese Patients With Steroid-dependent/Refractory Chronic Graft-Versus-Host Disease. [2021]