Ibrutinib for Graft-versus-Host Disease

Recruiting at 47 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

59 Participants Needed

Trial Summary

What is the purpose of this trial?

Dose Finding and Safety Study of Ibrutinib in Pediatric Subjects with Chronic Graft Versus Host Disease (cGVHD)

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.

What data supports the effectiveness of the drug ibrutinib for treating 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 rates. It works by targeting specific cells involved in the disease, and has been approved by the FDA for this use based on its effectiveness in clinical trials. ^{1 2 3 4 5}

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

Ibrutinib, also known as Imbruvica, has been used to treat graft-versus-host disease, but it comes with some risks. It can cause serious side effects like bleeding, infections, heart problems, high blood pressure, and other issues. Common side effects include muscle pain, fever, pneumonia, stomach pain, mouth sores, diarrhea, and headaches. ^{1 2 4 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 pediatric patients with chronic graft-versus-host disease (cGVHD) after other treatments have failed, and it works by targeting specific proteins in immune cells to reduce disease severity. It offers a new option for patients who do not respond to standard corticosteroid treatments. ^{1 2 3 4 8}

Research Team

Gauri Sunkersett

Principal Investigator

Pharmacyclics LLC.

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

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, 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, 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 (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. 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]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Ibrutinib: Pediatric First Approval. [2023]

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

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

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

Ibrutinib for chronic graft-versus-host disease after failure of prior therapy. [2022]