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

20 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Ibrutinib for treating mantle cell lymphoma?

Ibrutinib has been approved by the FDA for treating mantle cell lymphoma in patients who have already tried other treatments, and it has shown clinical benefits when combined with other drugs like rituximab. However, some patients may experience resistance to the drug, leading to relapses. ^{1 2 3 4 5}

Is ibrutinib safe for humans?

Ibrutinib, also known as Imbruvica, has been approved by the FDA for treating mantle cell lymphoma and other B-cell cancers. It has an acceptable safety profile, with less than 10% of patients stopping treatment due to side effects. ^{1 3 6 7 8}

How is the drug ibrutinib unique for treating mantle cell lymphoma?

Ibrutinib is unique because it is an oral medication that specifically targets Bruton's tyrosine kinase (BTK), a protein involved in the growth of cancer cells, making it effective for patients with relapsed or refractory mantle cell lymphoma. It has been shown to improve progression-free survival and overall response rates compared to other treatments. ^{1 2 3 9 10}

What is the purpose of this trial?

This phase II trial studies how well ibrutinib works in treating participants with untreated high risk smoldering mental cell lymphoma. Ibrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Research Team

Luhua (Michael) Wang

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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, 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 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]

References

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

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

2. Germany pubmed.ncbi.nlm.nih.gov

[scRNA-sequencing uncovers metabolism and CD52 as new targets in ibrutinib-surviving mantle cell lymphoma cells]. [2022]

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

Ibrutinib approved for mantle cell lymphoma. [2021]

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

Postibrutinib outcomes in patients with mantle cell lymphoma. [2022]

5. United States 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. [2022]

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

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

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

Ibrutinib: first global approval. [2022]

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

Activity of ibrutinib in mantle cell lymphoma patients with central nervous system relapse. [2021]

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

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

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

Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study. [2022]