Ibrutinib for Graft-versus-Host Disease

No longer recruiting at 59 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Pharmacyclics LLC.

Disqualifiers: Uncontrolled infection, Bleeding disorders, Active HCV/HBV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: Unknown

Duration: Until RPED is determined

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called ibrutinib (Imbruvica) to determine the right dose and ensure its safety for children with chronic graft-versus-host disease (cGVHD). This condition can occur after a stem cell transplant when the donated cells attack the recipient's body. The trial aims to help children with moderate to severe cGVHD, particularly when other treatments have failed or if a new diagnosis requires medication. Children who have undergone a stem cell transplant and face these specific challenges might be suitable for this study. As a Phase 1, Phase 2 trial, this research focuses on understanding the treatment's effects and measuring its efficacy in an initial, smaller group, offering participants a chance to contribute to important advancements in cGVHD treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that ibrutinib is generally well-tolerated by patients with chronic graft-versus-host disease (cGVHD). Studies have found it safe for those who have tried other treatments but still need help. Common side effects include diarrhea, bruising, and fatigue, similar to those from other ibrutinib treatments. Notably, the FDA has already approved ibrutinib for treating cGVHD in adults, and it may also benefit younger patients. While this trial seeks to determine the right dose for children, the existing approval suggests the drug is safe enough for further study in this new group. ^{1 2 3 4 5}

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

Ibrutinib is unique because it targets Bruton's tyrosine kinase (BTK), which plays a crucial role in the immune response involved in chronic graft-versus-host disease (cGVHD). Unlike traditional immunosuppressants like prednisone and cyclosporine that broadly dampen the immune system, ibrutinib specifically interrupts the signaling pathways that drive the disease, potentially leading to fewer side effects. Researchers are excited about ibrutinib because it offers a more targeted approach to managing cGVHD, which could improve outcomes and quality of life for patients, especially those who have not responded well to existing therapies.

What evidence suggests that ibrutinib might be an effective treatment for chronic graft-versus-host disease?

Research has shown that ibrutinib can effectively treat chronic graft-versus-host disease (cGVHD), especially when other treatments have failed. One study found that ibrutinib improved symptoms in 83.4% of cGVHD patients after 24 weeks, indicating many patients experienced relief. It also reduced the need for steroids, which are commonly used to treat cGVHD but can have serious side effects. Improvements appeared in various parts of the body affected by the disease, demonstrating ibrutinib's broad effectiveness. This promising evidence suggests that ibrutinib could be a valuable option for managing cGVHD. Participants in this trial will receive ibrutinib to further evaluate its effectiveness and determine the Recommended Pediatric Equivalent Dose (RPED) for younger patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Gauri Sunkersett

Principal Investigator

Pharmacyclics LLC.

Are You a Good Fit for This Trial?

This trial is for children and young adults who have chronic Graft Versus Host Disease (cGVHD) after a stem cell transplant. It's open to those aged 1-12 for Part A, and 1-22 for Part B, who've tried at least one treatment without success or are newly diagnosed needing systemic therapy. Participants should be fairly active (performance status ≥60). Those with uncontrolled infections, hepatitis, only genito-urinary cGVHD, recent investigational drugs or donor lymphocyte infusions can't join.

Inclusion Criteria

I can care for myself but may need occasional help.

I have chronic GVHD that didn't improve after at least one treatment.

I have a new, severe immune reaction after a transplant needing strong medication.

Exclusion Criteria

I have a known bleeding disorder.

My cancer is getting worse or I have a disease after a transplant.

Received an investigational agent within 28 days before enrollment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral ibrutinib once daily to determine the Recommended Pediatric Equivalent Dose (RPED)

Until RPED is determined

Continuation

Participants continue receiving daily ibrutinib at the RPED

Up to 5 years

Follow-up

Participants are monitored for safety, immune reconstitution, and growth parameters

Up to 5 years post enrollment

What Are the Treatments Tested in This Trial?

Interventions

• Ibrutinib

Trial Overview The study is testing the safety and appropriate dosing of Ibrutinib in pediatric patients with cGVHD. This phase involves finding the right dose (Phase 1) and then checking its safety profile more broadly (Phase 2).

How Is the Trial Designed?

Group I: Phase 1/2 Experimental Treatment 1 Intervention

Part A: Subjects ≥1 to \<12 years of age with moderate or severe cGVHD after failure of 1 or more lines of systemic therapy, will receive oral ibrutinib once daily to determine Recommended Pediatric Equivalent Dose (RPED). Part A Continuation: Subjects participating in Part A may continue receiving daily ibrutinib until the RPED is determined, at which time their dose may be adjusted to the RPED. Part B: Subjects ≥1 to \<12 years of age( upper age limit is \< 22 years) with moderate or severe cGVHD after failure of 1 or more lines of systemic therapy or with newly diagnosed moderate or severe cGVHD will be dosed at the RPED. Subjects ≥12 will be given 420mg orally ibrutinib once daily.

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?

Pharmacyclics LLC.

Lead Sponsor

Trials

114

Recruited

13,800+

Dr. Maky Zanganeh

Pharmacyclics LLC.

Chief Executive Officer

Degree from Louis Pasteur University in Strasbourg, France; MBA from Schiller International University in France

Dr. Ellie Im

Pharmacyclics LLC.

Chief Medical Officer

MD from an unspecified institution

Janssen Research & Development, LLC

Industry Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

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 (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]

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, 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, 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]

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

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36608310/

Ibrutinib for First-Line Treatment of Chronic Graft-Versus- ... Improvement in overall Lee cGVHD Symptom Scale was 43% (ibrutinib-prednisone) and 31% (placebo-ibrutinib; P = .07). Median OS was not reached in ...

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/PMC10909101/

Efficacy and Safety of Ibrutinib for Chronic Graft-Versus ... Ibrutinib is a safe and effective therapy choice for individuals with cGVHD who have tried other treatments or are dependent on steroids, according to the ...

9. 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 showed an acceptable safety profile in this pretreated cGVHD patient population, with AEs similar to those observed in ibrutinib-treated patients ...

10. 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 ...