Ibrutinib + Nivolumab for Hodgkin's Lymphoma

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ohio State University Comprehensive Cancer Center

Must not be taking: BTK inhibitors, Warfarin, CYP3A inhibitors

Disqualifiers: HIV, Hepatitis B/C, Cardiovascular, 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

Compensation: Varies

Number of Visits: 16

Duration: 48 weeks

18 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you require certain medications like strong CYP3A inhibitors or anticoagulants like warfarin. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination Ibrutinib and Nivolumab for Hodgkin's Lymphoma?

Research suggests that combining Ibrutinib with Nivolumab may enhance the immune response in Hodgkin's Lymphoma, potentially leading to deeper and more lasting effects. Additionally, studies in other types of lymphoma have shown that this combination can have synergistic antitumor effects, indicating its potential effectiveness. ^{1 2 3 4 5}

Is the combination of Ibrutinib and Nivolumab safe for humans?

The combination of Ibrutinib and Nivolumab has been studied for safety in patients with relapsed or refractory B-cell diseases, showing a safety profile consistent with known effects of each drug. Common side effects include diarrhea, fatigue, and nausea, with some immune-related side effects reported. ^{1 3 6 7 8}

How is the drug combination of Ibrutinib and Nivolumab unique for treating Hodgkin's Lymphoma?

The combination of Ibrutinib and Nivolumab is unique because it aims to enhance the immune response against Hodgkin's Lymphoma by combining a Bruton's tyrosine kinase inhibitor (Ibrutinib) with an immune checkpoint inhibitor (Nivolumab), potentially leading to deeper and more durable responses compared to using checkpoint inhibitors alone. ^{1 3 9 10 11}

What is the purpose of this trial?

This phase II trial studies how well ibrutinib and nivolumab work in treating patients with classical Hodgkin lymphoma that has come back or has not responded to treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as nivolumab, may block cancer growth in different ways by targeting certain cells. Giving ibrutinib and nivolumab may work better in treating patients with classical Hodgkin lymphoma.

Research Team

Lapo Alinari, MD, PhD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with classical Hodgkin lymphoma that has returned or hasn't responded to treatment. They must have had at least one prior therapy, not be pregnant or nursing, and agree to use contraception. People can't join if they've had certain other cancers, severe heart disease, gastrointestinal issues, CNS lymphoma involvement, significant liver impairment, a history of stroke recently, ongoing immunosuppression (except low-dose steroids), active autoimmune diseases or need strong CYP3A inhibitors.

Inclusion Criteria

I have had a transplant using my own cells before.

I have previously been treated with nivolumab.

I am not planning to undergo a transplant using my own cells.

Exclusion Criteria

I do not have serious heart problems like recent heart attacks or uncontrolled heart rhythm issues.

My lymphoma has spread to my brain or spinal cord.

I need treatment with a strong medication that affects liver enzymes.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ibrutinib orally once daily and nivolumab intravenously every 21 days for up to 16 courses

48 weeks

16 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Treatment Details

Interventions

• Ibrutinib
• Nivolumab

Trial Overview The trial tests how well the combination of Ibrutinib (an enzyme blocker) and Nivolumab (a monoclonal antibody) works in treating relapsed/refractory classical Hodgkin lymphoma compared to previous treatments. It's a phase II study which means it focuses on the effectiveness and further examines side effects.

Participant Groups

Group I: Treatment (ibrutinib, nivolumab) Experimental Treatment 3 Interventions

Patients receive ibrutinib PO QD on days 1-21 and nivolumab IV continuously over 60 minutes on day 1. Treatment with nivolumab repeats every 21 days for up to 16 courses and treatment with ibrutinib continues in the absence of disease progression or unacceptable toxicity.

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?

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials

350

Recruited

295,000+

Findings from Research

In a phase II clinical trial involving 17 patients with relapsed or refractory classical Hodgkin lymphoma, the combination of nivolumab and ibrutinib resulted in a complete response rate of 29.4%, which did not meet the target of 50%.

Despite not achieving the primary efficacy endpoint, the treatment showed promising durability of responses, with a median progression-free survival of 17.3 months, suggesting that further studies on this combination therapy are needed, especially for patients who have previously progressed on checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 2 Trial of Ibrutinib and Nivolumab in Patients with Relapsed or Refractory Classical Hodgkin's Lymphoma. Hanel, W., Shindiapina, P., Bond, DA., et al.[2023]

Ibrutinib is a targeted therapy specifically designed for treating chronic lymphocytic leukemia (CLL), which is a type of cancer that affects the blood and bone marrow.

This novel treatment works by inhibiting Bruton's tyrosine kinase (BTK), a key enzyme that helps cancer cells survive and proliferate, leading to improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. Parmar, S., Patel, K., Pinilla-Ibarz, J.[2021]

The combination of ibrutinib and nivolumab demonstrated an acceptable safety profile in 141 patients with relapsed or refractory B-cell malignancies, with only one dose-limiting toxicity reported, indicating that this treatment approach is generally safe for patients.

Preliminary results showed promising efficacy, with overall response rates of 61% in high-risk chronic lymphocytic leukaemia, 33% in follicular lymphoma, and 36% in diffuse large B-cell lymphoma, suggesting that this combination therapy could be effective for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of ibrutinib in combination with nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: a phase 1/2a study. Younes, A., Brody, J., Carpio, C., et al.[2021]

In a phase 1b/2 study involving 61 patients with relapsed/refractory follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL), the combination of ibrutinib and durvalumab showed an overall response rate of 25%, with the highest response in non-GCB DLBCL patients (38%).

The treatment was generally well-tolerated, with common side effects including diarrhea, fatigue, and nausea, and a notable 20% of patients experienced immune-related adverse events, indicating that while the combination therapy is effective, it also carries additional risks compared to single-agent treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of ibrutinib in combination with durvalumab in patients with relapsed or refractory follicular lymphoma or diffuse large B-cell lymphoma. Herrera, AF., Goy, A., Mehta, A., et al.[2021]

In a phase 1b trial involving 137 patients with relapsed/refractory lymphoid malignancies, the combination of nivolumab with ipilimumab or lirilumab showed significant activity in classical Hodgkin lymphoma, with overall response rates of 74% and 76%, respectively.

However, the combination therapies did not demonstrate a meaningful improvement in efficacy compared to single-agent nivolumab, and the combination with ipilimumab resulted in higher rates of severe treatment-related adverse events (29%) compared to lirilumab (15%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1b study of dual PD-1 and CTLA-4 or KIR blockade in patients with relapsed/refractory lymphoid malignancies. Armand, P., Lesokhin, A., Borrello, I., et al.[2021]

Ibrutinib is an effective oral treatment for patients with relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia (CLL), showing a 68% overall response rate in MCL and significant improvements in progression-free survival and overall survival in CLL patients, including those with specific genetic mutations.

The drug has a good safety profile, with less than 10% of patients discontinuing treatment due to adverse effects, making it a promising option for patients with various B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ibrutinib: A new drug of B-cell malignancies]. Thieblemont, C.[2021]

The combination of rituximab and ibrutinib in a 57-year-old patient with mantle cell lymphoma led to a severe disseminated enterovirus infection, highlighting the significant risk of immunodeficiency and severe immune-related side effects from this treatment regimen.

High-dose intravenous immunoglobulins were effective in clearing the virus and restoring organ function, suggesting that this treatment should be considered for patients experiencing severe enterovirus infections while on rituximab and ibrutinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Life-threatening disseminated enterovirus infection during combined rituximab and ibrutinib maintenance treatment for mantle cell lymphoma: a case report. Higer, M., Cana, D., Podlech, J., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

A Phase 2 Trial of Ibrutinib and Nivolumab in Patients with Relapsed or Refractory Classical Hodgkin's Lymphoma. [2023]

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

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Safety and activity of ibrutinib in combination with nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: a phase 1/2a study. [2021]

4. England pubmed.ncbi.nlm.nih.gov

A Phase I/II first-line study of R-CHOP plus B-cell receptor/NF-κB-double-targeting to molecularly assess therapy response. [2020]

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

Biomarkers of response to ibrutinib plus nivolumab in relapsed diffuse large B-cell lymphoma, follicular lymphoma, or Richter's transformation. [2021]

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

Safety and activity of ibrutinib in combination with durvalumab in patients with relapsed or refractory follicular lymphoma or diffuse large B-cell lymphoma. [2021]

7. England pubmed.ncbi.nlm.nih.gov

A phase 1b study of dual PD-1 and CTLA-4 or KIR blockade in patients with relapsed/refractory lymphoid malignancies. [2021]

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

Emerging role of novel therapies in Hodgkin lymphoma: proceed with caution. [2023]

9. France pubmed.ncbi.nlm.nih.gov

[Ibrutinib: A new drug of B-cell malignancies]. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Life-threatening disseminated enterovirus infection during combined rituximab and ibrutinib maintenance treatment for mantle cell lymphoma: a case report. [2021]

11. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety and efficacy analysis of ibrutinib in 32 patients with CLL and various B-cell lymphomas: real-world data from a single-center study in Turkey. [2022]