Ibrutinib + Rituximab for Mantle Cell Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Warfarin, Strong CYP3A4/5 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

Compensation: Varies

Number of Visits: 1

Duration: Up to 2 years

113 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase II trial studies how well ibrutinib and rituximab work in treating patients with mantle cell lymphoma that has come back or has not responded to treatment or older patients with newly diagnosed mantle cell lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, may find cancer cells and help kill them. Giving ibrutinib and rituximab may be an effective treatment for mantle cell lymphoma.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking warfarin or strong CYP3A4/5 inhibitors, you may need to stop them as they are not allowed during the trial.

Is the combination of Ibrutinib and Rituximab safe for humans?

Ibrutinib and Rituximab have been studied for safety in treating mantle cell lymphoma and other conditions. Ibrutinib can cause side effects like diarrhea, infections, bleeding issues, and heart problems such as atrial fibrillation (irregular heartbeat). These drugs have shown a generally well-tolerated safety profile, but it's important to consider potential side effects and interactions with other medications. ^{1 2 3 4 5}

How is the drug combination of Ibrutinib and Rituximab unique for treating mantle cell lymphoma?

The combination of Ibrutinib and Rituximab is unique because it targets mantle cell lymphoma cells more effectively by combining Ibrutinib's ability to inhibit B-cell activity with Rituximab's targeting of B lymphocytes, potentially leading to more potent antitumor activity compared to using Ibrutinib alone. ^{1 2 6 7 8}

What data supports the effectiveness of the drug combination Ibrutinib and Rituximab for treating Mantle Cell Lymphoma?

Research shows that Ibrutinib, when combined with Rituximab, can be effective for patients with mantle cell lymphoma, especially those who have already tried other treatments. In one study, adding Rituximab to Ibrutinib helped target cancer cells more effectively, potentially leading to better outcomes. ^{1 2 3 7 9}

Who Is on the Research Team?

Preetesh Jain, MD, PHD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with relapsed/refractory Mantle Cell Lymphoma (MCL) or those over 65 newly diagnosed with MCL. Participants need functioning kidneys, acceptable liver function, and no major heart issues. They must not be pregnant, have HIV/Hepatitis B infection, or have taken Ibrutinib before.

Inclusion Criteria

I have signed a consent form for treatment of my relapsed or refractory MCL.

I have signed the consent form for my relapsed/refractory MCL treatment study.

My platelet count is at least 30,000/mm^3, or 15,000/mm^3 with bone marrow cancer.

Exclusion Criteria

Newly diagnosed MCL: Known HIV infection; patients with active hepatitis B infection (not including patients with prior hepatitis B vaccination; or positive serum Hepatitis B antibody); known hepatitis C infection is allowed as long as there is no active disease and is cleared by GI consultation

I have heart problems like uncontrolled heart rhythm issues or recent heart attack.

I have a cancer that is more dangerous to my health than my newly diagnosed MCL.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ibrutinib daily and rituximab on a specified schedule for up to 2 years

Up to 2 years

Rituximab on days 1, 8, 15, 22 of course 1; day 1 of courses 3-8; and day 1 of every other course thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year every 3 months, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Ibrutinib
• Rituximab

Trial Overview The effectiveness of combining Ibrutinib and Rituximab to treat MCL is being tested. Ibrutinib blocks enzymes that cancer cells need to grow while Rituximab targets cancer cells directly. This phase II trial aims to see if this combination improves treatment outcomes.

How Is the Trial Designed?

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

Patients receive ibrutinib PO daily on days 1-28 and rituximab IV over 4-8 hours on days 1, 8, 15, and 22 of course 1; on day 1 of courses 3-8; and on day 1 of every other course for all subsequent courses. Treatment with rituximab repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Courses with ibrutinib repeat every 28 days 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

In a phase 2 trial involving 50 patients with relapsed or refractory mantle cell lymphoma, the combination of ibrutinib, lenalidomide, and rituximab resulted in a high overall response rate of 76%, with 56% achieving a complete response, suggesting this triplet therapy is effective.

While the treatment showed promising efficacy, it was associated with significant adverse events, including neutropenia in 38% of patients and three treatment-related deaths, highlighting the need for careful monitoring and further evaluation in randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial. Jerkeman, M., Eskelund, CW., Hutchings, M., et al.[2022]

In a phase 2 study involving 50 patients with relapsed or refractory mantle cell lymphoma, the combination of ibrutinib and rituximab resulted in an impressive 88% objective response rate, with 44% of patients achieving a complete response.

The treatment was generally well tolerated, with the most common serious side effect being atrial fibrillation in 12% of patients, indicating that while effective, monitoring for cardiac issues is important during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib in combination with rituximab in relapsed or refractory mantle cell lymphoma: a single-centre, open-label, phase 2 trial. Wang, ML., Lee, H., Chuang, H., et al.[2021]

Bruton's tyrosine kinase inhibitors, such as ibrutinib, acalabrutinib, and zanubrutinib, are effective and well-tolerated treatment options for patients with mantle cell lymphoma who have already undergone one line of therapy.

These inhibitors offer a promising alternative for patients who experience relapse or drug resistance after initial chemo-immunotherapy, highlighting the need for novel treatment strategies in this aggressive lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of Bruton's tyrosine kinase inhibitors in the management of mantle cell lymphoma. Hanna, KS., Campbell, M., Husak, A., et al.[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]

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]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial. [2022]

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

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

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

Ibrutinib in combination with rituximab in relapsed or refractory mantle cell lymphoma: a single-centre, open-label, phase 2 trial. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

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

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

Ibrutinib-rituximab followed by R-HCVAD as frontline treatment for young patients (≤65 years) with mantle cell lymphoma (WINDOW-1): a single-arm, phase 2 trial. [2022]

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

Ibrutinib (Imbruvica). Relapsed chronic lymphocytic leukaemia and mantle cell lymphoma: uncertain impact on survival. [2021]

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

The role of Bruton's tyrosine kinase inhibitors in the management of mantle cell lymphoma. [2021]

8. 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]

9. 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]