Ibrutinib for Mantle Cell Lymphoma

Overseen By Michael Wang, MD, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anticoagulants, CYP3A inhibitors

Disqualifiers: Uncontrolled hypertension, Diabetes, HIV, 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: 2

Duration: 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of the drug ibrutinib (Imbruvica) for individuals with untreated high-risk smoldering mantle cell lymphoma, a type of blood cancer. Ibrutinib blocks enzymes that aid tumor growth, potentially stopping or slowing the cancer. The trial seeks individuals who have not yet received treatment for this condition and have remained stable without disease progression for 3-6 months. Those with specific cancer markers, such as certain gene mutations or tumor sizes, may be suitable candidates. Participants will take ibrutinib daily in cycles, provided the disease does not progress and side effects remain manageable. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant findings.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you require continuous treatment with strong CYP3A inhibitors or need anticoagulation with warfarin. 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 well-tolerated by patients with mantle cell lymphoma (MCL). One study found that patients taking ibrutinib had a good safety profile, with serious side effects being uncommon. Another study from the UK, involving many MCL patients, confirmed that ibrutinib is both effective and safe. However, some patients in real-world settings experienced side effects that limited their dosage. Overall, while ibrutinib is mostly safe, some individuals might experience significant side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ibrutinib is unique because it targets the Bruton's tyrosine kinase (BTK) enzyme, which plays a key role in the growth and survival of cancer cells in mantle cell lymphoma. Unlike the standard chemotherapy treatments, which can affect both cancerous and healthy cells, ibrutinib specifically disrupts pathways that are crucial for the cancer cells, potentially leading to fewer side effects. Researchers are excited about ibrutinib because it offers a targeted approach, which may improve outcomes and quality of life for patients with this challenging condition.

What evidence suggests that ibrutinib might be an effective treatment for mantle cell lymphoma?

Research has shown that ibrutinib, the treatment under study in this trial, effectively treats mantle cell lymphoma (MCL), a type of blood cancer. Studies have found that patients with relapsed or refractory (R/R) MCL who took ibrutinib had response rates between 62.7% and 93.8%, indicating that many patients experienced their cancer shrinking or remaining stable. Additionally, combining ibrutinib with other treatments has extended the time patients live without their disease worsening. These findings suggest that ibrutinib could be a promising option for those with untreated high-risk smoldering MCL. ^{1 6 7 8 9}

Who Is on the Research Team?

Luhua (Michael) Wang

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with untreated high-risk smoldering mantle cell lymphoma (MCL) who have never received treatment, have measurable disease less than or equal to 5 cm, and are in good general health. They must be able to swallow capsules and agree to use effective birth control methods. People with blastoid or pleomorphic MCL variants, bulky tumors over 5 cm, certain heart conditions, severe liver impairment, recent major surgery or live vaccines, bleeding disorders, uncontrolled infections or other serious medical issues cannot join.

Inclusion Criteria

My cancer has not worsened in the last 3-6 months according to scans.

My MCL diagnosis is confirmed with specific markers or classic signs in a biopsy.

I have never received any treatment for my condition.

Exclusion Criteria

Risk factors including clinically significant disease related symptoms, Blastoid variant histology, Pleomorphic variant histology, Ki-67 > 30%, Bulky tumors > 5 cm, CNS involvement at diagnosis, Prior treatment for mantle cell lymphoma, Prior exposure to BTK inhibitor, Pregnant or breastfeeding females, Known history of HIV, HCV, or HBV, History of central nervous system lymphoma, History of stroke or intracranial hemorrhage within 6 months, Clinically significant cardiovascular disease, Inability to swallow capsules, Concomitant anticoagulation with warfarin, Chronic liver disease meeting Child-Pugh class C, Uncontrolled active systemic infection, Major surgery within 4 weeks of first dose of study drug, Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug, Recent infection requiring systemic treatment within 14 days before the first dose of study drug, Known bleeding disorders, Unresolved toxicities from prior anticancer therapy, Concurrent systemic immunosuppressant therapy within 21 days of the first dose of study drug

I do not have any serious medical conditions that would make it unsafe for me to participate.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ibrutinib orally once daily on days 1-28, with courses repeating every 28 days for up to 5 years

5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

6 months to 2 years

Every 2 months for 6 months, then every 2-4 months for 2 years, then every 4-6 months thereafter

What Are the Treatments Tested in This Trial?

Interventions

• Ibrutinib

Trial Overview The trial is testing the effectiveness of Ibrutinib in participants with untreated high-risk smoldering MCL. Ibrutinib is a medication that may inhibit tumor growth by blocking enzymes needed for cell growth. This phase II study aims to understand how well it works before any traditional treatment starts.

How Is the Trial Designed?

Group I: Treatment (ibrutinib) Experimental Treatment 1 Intervention

Participants receive ibrutinib PO QD on days 1-28. Courses repeat every 28 days for 5 years 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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Ibrutinib, an oral Bruton tyrosine kinase inhibitor, demonstrated rapid and dramatic responses in 3 patients with symptomatic CNS relapse of mantle cell lymphoma, leading to almost immediate recovery from symptoms.

Pharmacokinetic analyses confirmed that ibrutinib effectively crosses the blood-brain barrier, with ongoing responses observed in patients from 2 months to 1 year after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of ibrutinib in mantle cell lymphoma patients with central nervous system relapse. Bernard, S., Goldwirt, L., Amorim, S., et al.[2021]

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]

Ibrutinib is a powerful oral medication that effectively treats relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia (CLL), showing high response rates and significantly improving survival outcomes, especially in patients with poor prognostic factors like chromosome 17 deletion (del 17p).

The drug has a good safety profile, with less than 10% of patients discontinuing treatment due to side effects, making it a promising option for patients with these types of blood cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: a review of its use in patients with mantle cell lymphoma or chronic lymphocytic leukaemia. Kim, ES., Dhillon, S.[2022]

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]

In a phase II study involving 50 previously untreated patients with indolent mantle cell lymphoma (MCL), the combination of ibrutinib and rituximab resulted in an impressive 80% complete response rate after 12 treatment cycles.

The treatment also led to undetectable minimal residual disease (MRD) in 87% of patients, allowing 69% of evaluable patients to safely discontinue ibrutinib after 2 years, although caution is advised for those with TP53 mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial. Giné, E., de la Cruz, F., Jiménez Ubieto, A., et al.[2022]

Citations

1. ashpublications.org ashpublications.org/bloodneoplasia/article/2/3/100128/537696/Real-world-outcomes-with-ibrutinib-in-relapsed-or

Real-world outcomes with ibrutinib in relapsed or refractory ... In conclusion, real-world outcomes after initiation of ibrutinib for R/R MCL were poorer than observed in clinical trials, and dose-limiting ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9715897/

Efficacy and safety of ibrutinib in mantle cell lymphoma The overall response rates (ORRs) of patients with R/R MCL receiving single-agent ibrutinib ranged between 62.7% to 93.8%, and the ORRs of ...

3. bloodresearch.or.kr bloodresearch.or.kr/journal/view.html?uid=2650&vmd=Full

A retrospective analysis of ibrutinib outcomes in relapsed ... Patients with RR-MCL, who received a median of three prior treatment modalities, including ibrutinib, responded for 21.6 months [24]. Moreover, ...

4. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(24)00184-3/fulltext

Ibrutinib combined with immunochemotherapy with or ... A recently published randomised trial had shown prolonged progression-free but not overall survival by adding ibrutinib to first-line rituximab– ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0006497124011121

Seven-year outcomes of venetoclax-ibrutinib therapy in ... In relapsed MCL, venetoclax-ibrutinib achieves 7-year PFS of 30%, TTF of 39%, OS of 43%, and durable remissions in 10 of 17 responders.

6. jnj.com jnj.com/innovativemedicine/emea/newsroom/european-commission-approves-imbruvica-ibrutinib-as-the-first-targeted-therapy-for-patients-with-previously-untreated-mantle-cell-lymphoma-who-would-be-eligible-for-autologous-stem-cell-transplant

European Commission approves IMBRUVICA® (ibrutinib) ... The trial enrolled 870 patients with previously untreated mantle cell lymphoma (MCL).2 The primary endpoint was failure-free survival (FFS).2 Overall survival ( ...

7. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/3661/489322/Effectiveness-and-Safety-of-Ibrutinib-in-Patients

Effectiveness and Safety of Ibrutinib in Patients with Mantle ... Effectiveness and safety of ibrutinib in patients with mantle cell lymphoma (MCL) in Belgian routine clinical practice: 3-year follow-up available.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9807478/

Ibrutinib in mantle cell lymphoma: a real-world ... involving a large real-world population of MCL patients from the UK confirmed the high efficacy and good safety profile of ibrutinib exclusively ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2950328025000639

Real-world outcomes with ibrutinib in relapsed or refractory ... Real-world outcomes after initiation of ibrutinib for R/R MCL were poorer than observed in clinical trials, and dose limiting toxicities were common.