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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of ibrutinib in preventing chronic graft-versus-host disease (GVHD) in individuals who have undergone a donor stem cell transplant. After such a transplant, donor cells can sometimes attack the body, leading to GVHD. Ibrutinib may prevent this by blocking a protein involved in the immune response. Suitable candidates for this trial have received a donor stem cell transplant and do not currently have uncontrolled GVHD or any signs of cancer recurrence. As a Phase 2 trial, this research measures ibrutinib's effectiveness in an initial, smaller group, offering participants the opportunity to contribute to significant medical advancements.

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.

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

Research has shown that ibrutinib is generally safe for patients with chronic graft-versus-host disease (cGVHD). In studies involving patients who had tried other treatments, ibrutinib often proved effective and was usually easy to tolerate. Common side effects included diarrhea, tiredness, and muscle pain, but most patients managed these. Additionally, the FDA has already approved ibrutinib for treating cGVHD, supporting its safety for this condition. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for GVHD?

Unlike the standard of care for preventing Graft-versus-Host Disease, which often includes immunosuppressive drugs like steroids, Ibrutinib acts on a different pathway. Ibrutinib is unique because it targets Bruton's tyrosine kinase, a key player in the immune system's signaling pathways. This targeted mechanism of action could potentially reduce the risk of severe side effects commonly associated with traditional immunosuppressants. Researchers are excited about Ibrutinib because it offers a promising alternative that may effectively prevent Graft-versus-Host Disease with potentially fewer complications.

What evidence suggests that ibrutinib might be an effective treatment for preventing chronic GVHD?

Research suggests that ibrutinib, which participants in this trial will receive, might help prevent chronic graft-versus-host disease (GVHD). It blocks a protein involved in the body's immune response. In earlier studies, ibrutinib showed promising results for patients who didn't respond to other treatments. One study found that ibrutinib helped 83.4% of patients after 24 weeks, based on specific criteria. Another study showed that patients taking ibrutinib with prednisone experienced significant symptom improvement compared to those taking a placebo. These findings suggest that ibrutinib may effectively prevent chronic GVHD after donor stem cell transplants. ^{1 6 7 8 9}

Who Is on the Research Team?

Mohamed A. Kharfan Dabaja, MD, MBA

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 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 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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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, 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]

Citations

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

Ibrutinib for Chronic Graft-Versus-Host Disease - NCBI - NIH Because of the early data indicating that ibrutinib can be an effective intervention for treatment-refractory CGvHD, as well as the relatively recent Health ...

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. ashpublications.org ashpublications.org/bloodadvances/article/9/5/1040/525803/Ibrutinib-for-therapy-of-steroid-refractory

Ibrutinib for therapy of steroid-refractory chronic graft-versus ... Responses were seen across involved organ sites, and steroid dose reduction was observed. Adverse events included diarrhea, fatigue, muscle ...

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

Ibrutinib for First-Line Treatment of Chronic Graft-Versus- ... Additional follow-up at 96 weeks demonstrated response rates of 27% (ibrutinib-prednisone) and 22% (placebo-prednisone; P = .43); 13 patients (14%) and nine ...

5. 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 ...

6. 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 ... Ibrutinib resulted in clinically meaningful responses with acceptable safety in patients with ≥1 prior treatments for cGVHD. Based on these results, ibrutinib ...

7. journal.waocp.org journal.waocp.org/article_89560_f1b7b2ebd250adb4a4d54c7946a57672.pdf,https:/www.ncbi.nlm.nih.gov/pubmed/33906311,https:/pubmed.ncbi.nlm.nih.gov/33906311/,https:/www.ncbi.nlm.nih.gov/pmc/articles/PMC8325144,http:/journal.waocp.org/article_90923_57a4d289251207d7a1dab7c72c2b4e9c.pdf

REVIEW Efficacy and Safety of Ibrutinib for Chronic Graft ... FDA review summary of patient-reported outcome results for ibrutinib in the treatment of chronic graft versus host disease. Qual Life Res ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2473952924006256

Ibrutinib for therapy of steroid-refractory chronic graft ... Responses were seen across involved organ sites, and steroid dose reduction was observed. Adverse events included diarrhea, fatigue, muscle ...

9. jnj.com jnj.com/media-center/press-releases/u-s-fda-approves-imbruvica-ibrutinib-as-first-and-only-btki-treatment-for-pediatric-patients-with-chronic-graft-versus-host-disease

U.S. FDA Approves IMBRUVICA® (ibrutinib) as First and ... IMBRUVICA® is now the only BTKi with 12 FDA approvals across seven indications, including five hematologic cancers and cGVHD.