Ibrutinib for Chronic Graft-versus-Host Disease

Not currently recruiting at 3 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if ibrutinib (Imbruvica) can treat chronic Graft-versus-Host Disease (cGVHD), a condition where donor cells attack the recipient’s body after a stem cell or bone marrow transplant. Researchers are investigating whether ibrutinib can block a protein that triggers this immune reaction, potentially serving as a first-line treatment for those newly diagnosed with moderate or severe cGVHD. Individuals recently diagnosed with moderate or severe cGVHD who have undergone a stem cell transplant might be suitable for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants, offering them a chance to contribute to significant advancements in cGVHD treatment.

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.

Is there any evidence suggesting that ibrutinib is likely to be safe for humans?

Earlier research has used ibrutinib to treat chronic graft-versus-host disease (cGVHD) in patients unresponsive to other treatments like steroids. These studies found no new safety issues with ibrutinib, indicating it was generally safe in these cases. The FDA has approved ibrutinib for adults with cGVHD who have not responded to other treatments, reflecting its good safety record. While individual reactions may vary, these studies have not reported any unexpected or severe side effects specifically for ibrutinib. Anyone considering joining a clinical trial should discuss potential risks and benefits with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for chronic graft-versus-host disease, which often relies heavily on corticosteroids, ibrutinib offers a different approach by targeting Bruton's tyrosine kinase (BTK). This unique mechanism of action helps modulate the immune response, potentially reducing the need for steroids and their associated side effects. Researchers are excited about ibrutinib because it provides a continuous, daily oral treatment option that could improve response rates and quality of life for patients without relying on corticosteroids.

What evidence suggests that ibrutinib might be an effective treatment for cGVHD?

Research shows that ibrutinib, administered without corticosteroids in this trial, may help treat chronic graft-versus-host disease (cGVHD). One study found that ibrutinib improved the condition in 83.4% of patients by week 24. Another study revealed that when combined with prednisone, 43% of patients experienced symptom improvement, compared to 31% with a placebo. Although ibrutinib is already approved for other uses, these studies suggest it could also be effective for cGVHD. Overall, this research highlights ibrutinib's potential to benefit people with cGVHD. ^{6 7 8 9 10}

Who Is on the Research Team?

Steven Z Pavletic, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 (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]

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) 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]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK603673/

Ibrutinib for Chronic Graft-Versus-Host Disease - NCBI - NIH There were no eligible studies identified that described the comparative clinical effectiveness of ibrutinib for the treatment of CGvHD; thus, no summary can be ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1473050224002337

Effectiveness of ibrutinib in the management of chronic ... Based on the NIH cGVHD Consensus Panel response criteria, ibrutinib treatment resulted in an ORR of 83.4 % for cGVHD at week 24, with 41.7 % of patients ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.00509

Ibrutinib for First-Line Treatment of Chronic Graft-Versus- ... 11). Improvement in overall Lee cGVHD Symptom Scale was 43% (ibrutinib-prednisone) and 31% (placebo-ibrutinib; P = .07). Median ...

4. network.nmdp.org network.nmdp.org/research/research-publications/ibrutinib-study-shows-the-need-for-effective-chronic-gvhd-treatment-options

Ibrutinib study shows the need for effective chronic GVHD ... There was a 43% improvement in the overall Lee cGVHD Symptom Scale for the ibrutinib-prednisone group compared to 31% for the placebo-prednisone group (not ...

5. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-ibrutinib-pediatric-patients-chronic-graft-versus-host-disease-including-new-oral

FDA approves ibrutinib for pediatric patients with chronic ... The median duration of response was 5.3 months (95% CI: 2.8, 8.8). The median time from first response to death or new systemic therapies for ...

6. imbruvica.com imbruvica.com/cgvhd

cGVHD Treatment | IMBRUVICA® (ibrutinib) IMBRUVICA® (ibrutinib) is a treatment option for patients 1 year and older with cGVHD after failure of systemic therapy, such as steroids.

7. imbruvicahcp.com imbruvicahcp.com/cgvhd

Chronic GVHD Treatment | IMBRUVICA® (ibrutinib) HCP Learn about IMBRUVICA® for patients with previously treated cGVHD. See Full Prescribing and Safety Information.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10082299/

Ibrutinib for First-Line Treatment of Chronic Graft-Versus- ... There was no statistical difference observed in the primary and secondary end points with ibrutinib-prednisone treatment. No new safety signals were observed ...

9. imbruvica.com imbruvica.com/cgvhd/imbruvica-for-cgvhd

IMBRUVICA® (ibrutinib) for Previously Treated Adult cGVHD IMBRUVICA® is the first FDA-approved therapy for adult chronic graft versus host disease (cGVHD) patients who have already been treated with other systemic ...

10. ashpublications.org ashpublications.org/blood/article/130/21/2243/36673/Ibrutinib-for-chronic-graft-versus-host-disease

Ibrutinib for chronic graft-versus-host disease after failure of ... This phase 1b/2, open-label, multicenter study was designed to determine the safety and efficacy of ibrutinib in patients who failed ≥1 therapy for cGVHD.