Ibrutinib + Pembrolizumab for Leukemia and Lymphoma

Overseen By Alexis Mark

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Joshua Brody

Must not be taking: Immunosuppressants, Steroids, Monoclonal antibodies, others

Disqualifiers: Immunodeficiency, Active TB, Autoimmune, 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

Compensation: Varies

Number of Visits: 2

Duration: up to 1 year

23 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have had certain treatments like chemotherapy or radiation therapy within 2 weeks before starting the trial, or if you are on systemic steroid therapy or other immunosuppressive treatments within 7 days before the trial.

What data supports the effectiveness of the drug combination Ibrutinib and Pembrolizumab for Leukemia and Lymphoma?

Research shows that Ibrutinib, when used alone or with other drugs, is effective in treating certain types of blood cancers like chronic lymphocytic leukemia and mantle cell lymphoma, with good response rates and survival benefits. Additionally, Ibrutinib has shown promising results when combined with immune therapies like nivolumab, suggesting potential benefits when combined with Pembrolizumab. ^{1 2 3 4 5}

Is the combination of Ibrutinib and Pembrolizumab safe for humans?

Ibrutinib (Imbruvica) has been shown to have an acceptable safety profile in treating certain types of leukemia and lymphoma, with less than 10% of patients stopping treatment due to side effects. However, there have been rare cases of serious bleeding events. While specific safety data for the combination with Pembrolizumab (KEYTRUDA) is not provided, Ibrutinib alone is generally considered tolerable. ^{1 2 4 6 7}

How is the drug combination of Ibrutinib and Pembrolizumab unique for treating leukemia and lymphoma?

The combination of Ibrutinib and Pembrolizumab is unique because it pairs Ibrutinib, an oral drug that blocks signals in cancer cells to stop their growth, with Pembrolizumab, an immune therapy that helps the body's immune system attack cancer cells. This dual approach targets cancer in two different ways, potentially offering a more effective treatment option for leukemia and lymphoma compared to traditional therapies. ^{4 6 8 9 10}

What is the purpose of this trial?

The purpose of this study is to determine the most appropriate dose for the combination of ibrutinib and pembrolizumab and to see if the combination is active for the disease. The study will monitor for any side effects and if the combination of ibrutinib and pembrolizumab works in the cancers being studied. There will be 2 experimental drugs given to the subject in this study. One experimental drug used in this study is called ibrutinib and the second is called pembrolizumab. This is the first time that ibrutinib will be used in combination with pembrolizumab. This combination is considered experimental. Experimental means that it is still being tested to see if it is safe and effective. Ibrutinib is a new drug known as a 'Bruton's Tyrosine Kinase (BTK) inhibitor'. Ibrutinib blocks an enzyme (protein) that affects how certain types of blood cancer cells grow and survive. Blocking this enzyme is a very important mechanism in killing blood cancer cells. Ibrutinib has been approved in the United States, Israel, and the European Union for use in adult patients with mantle cell lymphoma (MCL) and adult patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy. Pembrolizumab is an antibody (a type of human protein) that is being tested to see if it will allow the body's immune system to work against tumor cells. Pembrolizumab is approved for use by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with melanoma (skin cancer) who have received prior treatments. Pembrolizumab is not FDA approved to treat patients with chronic lymphocytic leukemia \[CLL\] and mantle cell lymphoma \[MCL\].

Research Team

Joshua Brody

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

Adults over 18 with chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) who can provide consent and have measurable disease. They must be in good health otherwise, not pregnant, agree to use contraception, and haven't used certain other treatments recently like immunosuppressives or live vaccines.

Inclusion Criteria

I am a man who can father a child and will use birth control during and for 4 months after the study.

Be willing and able to provide written informed consent/assent for the trial

I agree to provide a recent biopsy sample of my tumor.

Exclusion Criteria

I haven't had cancer treatment with antibodies in the last 4 weeks or still have side effects.

Has a condition, therapy, or abnormality that might confound trial results or interfere with participation

Has psychiatric or substance abuse disorders that would interfere with trial requirements

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead-in Treatment

Participants receive a 28-day lead-in of ibrutinib

4 weeks

1 visit (in-person)

Treatment

Participants receive a 21-day cycle of pembrolizumab and daily ibrutinib

up to 1 year

1 visit every 21 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 1 year

Treatment Details

Interventions

• Ibrutinib
• Pembrolizumab

Trial Overview The trial is testing a combination of two drugs: Ibrutinib, which blocks an enzyme that helps blood cancer cells grow; and Pembrolizumab, an antibody designed to help the immune system fight tumor cells. This study aims to find the right dose and see if this experimental combo works for CLL/MCL.

Participant Groups

Group I: Participants with MCL Experimental Treatment 2 Interventions

Participants with relapsed/ refractory Mantle Cell Lymphoma (MCL)

Group II: Participants with CLL Experimental Treatment 2 Interventions

Participants with relapsed/ refractory Chronic Lymphocytic Leukemia (CLL) or 17p- CLL

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?

Joshua Brody

Lead Sponsor

Trials

2

Recruited

40+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

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]

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]

Ibrutinib (Imbruvica) is an effective treatment for chronic lymphocytic leukemia, targeting specific pathways to inhibit cancer cell growth.

Tasimelteon (Hetlioz) is beneficial for individuals with non-24-hour sleep-wake disorder, helping to regulate sleep patterns, while anti-inhibitor coagulant complex (Feiba) is used to prevent or reduce bleeding episodes in patients with hemophilia A or B, demonstrating its efficacy in managing bleeding risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical approval update. Goldenberg, MM.[2021]

Ibrutinib, a Bruton's kinase inhibitor, has shown a high overall response rate of 68% in patients with relapsed or refractory mantle cell lymphoma, with a median progression-free survival of 13.9 months, indicating its efficacy as a treatment option.

In a phase 3 trial for chronic lymphocytic leukemia, ibrutinib demonstrated a significantly higher response rate (43% vs. 4% for ofatumumab) and improved overall survival (90% vs. 81% at 12 months), while being well tolerated with no dose-limiting toxicity, making it a suitable option for older patients and those not eligible for intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of a novel, Bruton's tyrosine kinase inhibitor, ibrutinib. Lee, CS., Rattu, MA., Kim, SS.[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]

Ibrutinib is the first FDA-approved drug that inhibits Burton's tyrosine kinase (BTK), effectively reducing B-cell proliferation and promoting apoptosis, making it a significant treatment for relapsed chronic lymphocytic leukemia and Waldenström's macroglobulinemia.

Despite its efficacy, ibrutinib can lead to serious side effects, including rare but severe hemorrhagic events, as demonstrated by a case of back pain caused by iliopsoas muscle hemorrhage in a patient after starting the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spontaneous Iliopsoas Muscle Hemorrhage Secondary to Ibrutinib (Imbruvica; Pharmacyclics): Brief Report. Sarcon, A., Botta, GP., Patel, N., et al.[2018]

Ibrutinib is a first-in-class oral Bruton's tyrosine kinase inhibitor that effectively blocks B-cell signaling, leading to reduced proliferation and increased cell death in B cell malignancies, including chronic lymphocytic leukaemia (CLL) and mantle cell lymphoma (MCL).

It has received FDA approval for treating MCL in previously treated patients based on phase Ib/II study results and is currently undergoing further phase III trials for CLL, diffuse large B cell lymphoma (DLBCL), and other B cell cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: first global approval. Cameron, F., Sanford, M.[2022]

The Phase III HELIOS trial is designed to evaluate the efficacy of adding ibrutinib to the standard treatment of bendamustine and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia, with a focus on progression-free survival as the primary endpoint.

Eligible patients will receive a maximum of six cycles of BR, and the study will also assess safety, overall survival, and patient-reported outcomes, providing a comprehensive evaluation of ibrutinib's benefits compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The HELIOS trial protocol: a phase III study of ibrutinib in combination with bendamustine and rituximab in relapsed/refractory chronic lymphocytic leukemia. Hallek, M., Kay, NE., Osterborg, A., et al.[2021]

Ibrutinib is an effective oral therapy for chronic lymphocytic leukaemia (CLL), small lymphocytic lymphoma, mantle cell lymphoma, and Waldenstrom's macroglobulinaemia, providing a significant alternative to traditional chemotherapy.

The You&i™ support program enhances patient experience by connecting them with nurses for guidance on treatment and side effects, demonstrating positive feedback from both patients and health professionals in a tested NHS hospital setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imbruvica®▾(ibrutinib) patient support programme for chronic lymphocytic leukaemia and mantle cell lymphoma. Murthy, V., Weaving, S., Paneesha, S.[2021]

References

1. 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]

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

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

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

Ibrutinib plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma. [2022]

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

Pharmaceutical approval update. [2021]

5. England pubmed.ncbi.nlm.nih.gov

A review of a novel, Bruton's tyrosine kinase inhibitor, ibrutinib. [2021]

6. France pubmed.ncbi.nlm.nih.gov

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

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

Spontaneous Iliopsoas Muscle Hemorrhage Secondary to Ibrutinib (Imbruvica; Pharmacyclics): Brief Report. [2018]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Ibrutinib: first global approval. [2022]

9. England pubmed.ncbi.nlm.nih.gov

The HELIOS trial protocol: a phase III study of ibrutinib in combination with bendamustine and rituximab in relapsed/refractory chronic lymphocytic leukemia. [2021]

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

Imbruvica®▾(ibrutinib) patient support programme for chronic lymphocytic leukaemia and mantle cell lymphoma. [2021]