Ibrutinib + Rituximab + Chemotherapy for Mantle Cell Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Warfarin, Strong CYP3A inhibitors

Disqualifiers: Uncontrolled hypertension, Diabetes, HIV, Hepatitis, 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: 24

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a drug combination—ibrutinib, rituximab, and chemotherapy—in treating mantle cell lymphoma. Ibrutinib, a targeted therapy, stops cancer cells from growing, while rituximab enables the immune system to attack these cells. The chemotherapy drugs work together to kill cancer cells and prevent their spread. Individuals newly diagnosed with mantle cell lymphoma who experience symptoms like pain or large tumors might be suitable for this trial. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from promising therapies.

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 treatment with strong CYP3A inhibitors or anticoagulation with warfarin. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of ibrutinib and rituximab is generally well-tolerated by patients with mantle cell lymphoma. Studies have found that this combination helps patients live longer without disease progression. However, some patients experienced side effects that required a reduced medication dose.

When rituximab is added to chemotherapy, studies indicate it can extend survival for patients with this type of lymphoma. Although chemotherapy can have side effects, this combination is usually manageable.

Patients should discuss possible side effects with their healthcare provider to understand how these treatments might affect them personally. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of ibrutinib and rituximab for mantle cell lymphoma because it offers a fresh approach compared to traditional chemotherapy. Ibrutinib works by specifically targeting and blocking a protein called Bruton's tyrosine kinase, which is crucial for the growth of cancer cells. This targeted action is unlike conventional drugs that affect both cancerous and healthy cells, potentially leading to fewer side effects. Additionally, combining ibrutinib with rituximab, which enhances the immune system’s ability to attack cancer cells, could improve treatment effectiveness and outcomes for patients.

What evidence suggests that this trial's treatments could be effective for mantle cell lymphoma?

Studies have shown that combining ibrutinib and rituximab effectively treats mantle cell lymphoma. Research indicates that this combination significantly improves progression-free survival, allowing patients to live longer without their cancer worsening. In older patients, these two drugs outperformed standard treatments. Specifically, the chance of staying progression-free for five years was 52% with this combination, compared to only 19% with other treatments. In this trial, participants will receive ibrutinib and rituximab as part of the treatment regimen, suggesting that this combination could be a strong option for fighting mantle cell lymphoma. ^{1 2 4 6 7}

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 young patients under 65 with newly diagnosed mantle cell lymphoma, who need immediate treatment and have measurable disease. They should be in good physical condition (ECOG <=2), have proper organ function, no serious medical conditions or active infections, and not be pregnant. High-risk factors like blastoid/pleomorphic variant or certain genetic mutations qualify them.

Inclusion Criteria

I am 65 years old or younger.

My cancer can be measured in two dimensions.

Platelet count > 100,000/mm^3 or >= 20,000/mm^3 with approval

Exclusion Criteria

I have a serious medical condition.

I am HIV positive.

I have an active hepatitis B or C infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Ibrutinib Plus Rituximab

Patients receive ibrutinib orally once daily and rituximab intravenously over several hours. Treatment repeats every 28 days for up to 12 cycles.

Up to 48 weeks

Monthly visits for 12 cycles

Consolidation Therapy

Patients receive a combination of rituximab, dexamethasone, cyclophosphamide, doxorubicin, vincristine, methotrexate, and cytarabine. Treatment repeats every 28 days for up to 8 cycles.

Up to 32 weeks

Monthly visits for 8 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 6 years

Every 4 months for 2 years, every 6 months for 2 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Cytarabine
• Dexamethasone
• Doxorubicin
• Doxorubicin Hydrochloride
• Ibrutinib
• Methotrexate
• Rituximab
• Vincristine

Trial Overview The study tests a combination of the drug Ibrutinib with Rituximab and other chemotherapy drugs to see if they work better together for treating mantle cell lymphoma. It aims to block cancer growth enzymes, help the immune system attack cancer cells, and kill or stop cancer cells from dividing.

How Is the Trial Designed?

Group I: Treatment (ibrutinib, rituximab, consolidation chemotherapy) Experimental Treatment 11 Interventions

PART I (IBRUTINIB PLUS RITUXIMAB): Patients receive ibrutinib PO QD on days 1-28 and rituximab IV over 6-8 hours on days 1, 8, 15, and 22 of cycle 1 and then over 4 hours on day 1 of cycles 3-12. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity or until patients achieve complete response. PART II (CONSOLIDATION THERAPY): Patients receive rituximab IV over 6 hours on day 1; dexamethasone PO or IV on days 1-4; cyclophosphamide IV over 3 hours BID on days 2-4; doxorubicin hydrochloride IV over 15-30 minutes on day 5; and vincristine sulfate IV over 15-30 minutes on day 5 of cycles 1, 3, 5, and 7. Patients also receive rituximab IV over 6 hours on day 1; methotrexate IV over 24 hours on day 2; and cytarabine IV over 2 hours BID on days 3 and 4 of cycles 2, 4, 6, and 8. Treatment repeats every 28 days for up to 8 cycles 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 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]

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 network meta-analysis of three randomized controlled trials involving 1459 patients with newly diagnosed mantle-cell lymphoma (MCL) ineligible for intensive therapy, the combination of ibrutinib plus bendamustine and rituximab (Ibru + BR) significantly improved progression-free survival (PFS) compared to other regimens like VR-CAP and R-CHOP.

Ibru + BR had a 94.9% probability of being the best treatment option for prolonging PFS, with no significant differences in adverse events compared to the other treatment regimens, indicating its efficacy and safety for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Superiority of ibrutinib plus bendamustine and rituximab in newly diagnosed patients with mantle-cell lymphoma ineligible for intensive therapy: A network meta-analysis. Sheng, Z., Wang, L.[2023]

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]

Citations

1. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)01432-1/fulltext

a randomised, open-label, phase 2/3 superiority trial The ENRICH trial demonstrated a significant improvement in progression-free survival for patients 60 years and older with mantle cell lymphoma ...

2. esmo.org esmo.org/oncology-news/significant-pfs-improvement-with-ibrutinib-rituximab-compared-to-immunochemotherapy-in-previously-untreated-patients-with-mantle-cell-lymphoma

Significant PFS Improvement with Ibrutinib-Rituximab ... Ibrutinib-rituximab was associated with a faster improvement in health-related quality-of-life compared with either of the immunochemotherapy ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/235/531189/Ibrutinib-Rituximab-Is-Superior-to-Rituximab

Ibrutinib-Rituximab Is Superior to Rituximab-Chemotherapy in ... Frontline Treatment with Ibrutinib with Rituximab (IR) Combination Is Highly Effective in Elderly (≥65 years) Patients with Mantle Cell Lymphoma ...

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

Efficacy and safety of ibrutinib in mantle cell lymphoma The highest progression-free survival (PFS) was reported in patients receiving ibrutinib and rituximab (43 months). The meta-analysis performed ...

5. onclive.com onclive.com/view/ibrutinib-plus-rituximab-shows-pfs-benefit-over-chemoimmunotherapy-in-untreated-mcl

Ibrutinib Plus Rituximab Shows PFS Benefit Over ... Ibrutinib plus rituximab showed superior PFS compared to R-CHOP in older MCL patients, with a 5-year PFS probability of 52% versus 19%.

6. 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 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12346063/

Real-world outcomes with ibrutinib in relapsed or refractory ... Patients receiving ibrutinib for R/R MCL in routine practice have inferior survival compared with trials. Dose-limiting toxicities on ibrutinib were common, ...