Personalized Therapy for Mantle Cell Lymphoma

Overseen By Michael) Wang, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Corticosteroids

Disqualifiers: Uncontrolled hypertension, Diabetes, Coronary artery disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find personalized treatments for individuals with mantle cell lymphoma (MCL), particularly if the cancer has returned or does not respond to current treatments. Researchers will use genetic testing to match patients with the most effective drugs based on specific genetic changes in their cancer cells. This approach is crucial for those whose MCL does not respond to BTK inhibitors, such as Zanubrutinib (Brukinsa). Suitable candidates have relapsed or hard-to-treat MCL and are willing to undergo genetic testing and biopsies. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to more effective, personalized treatments for MCL.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop all current medications. However, you must not have had chemotherapy within 2 weeks, certain other treatments within specified time frames, or be on high-dose corticosteroids. It's best to discuss your specific medications with the trial team.

What prior data suggests that these personalized therapies are safe for treating mantle cell lymphoma?

Studies have shown that zanubrutinib, a type of medication, is generally well-tolerated by patients with mantle cell lymphoma. A large safety study involving 1,550 patients identified common side effects, such as changes in the number of certain white blood cells, which were not severe for most people. Serious side effects, like major bleeding, occurred in fewer than 10% of patients.

Research indicates that zanubrutinib works well for many patients and is considered safe overall. While some side effects may occur, the treatment is generally safe for those with relapsed or refractory mantle cell lymphoma. For those considering a trial with zanubrutinib, existing data suggests it is a relatively safe option, though individual experiences can vary. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the personalized therapy for Mantle Cell Lymphoma because it tailors treatment based on individual mRNA analysis, potentially increasing effectiveness compared to standard chemotherapy and immunotherapy options. Unlike traditional treatments, which follow a one-size-fits-all approach, this therapy adjusts to the genetic makeup of each patient's cancer, allowing for more precise targeting of the disease. This personalized method could lead to better patient outcomes and fewer side effects, making it a promising advancement in lymphoma care.

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

Research has shown that zanubrutinib, a type of medication, effectively treats mantle cell lymphoma (MCL), especially when other treatments have failed. Studies have found that 84% of patients responded to zanubrutinib, with 25% experiencing a complete response, meaning their cancer became undetectable. Another study reported that 83.7% of patients responded, with 77.9% achieving a complete response. These findings highlight zanubrutinib's potential to successfully treat MCL that has returned or resisted other treatments. Participants in this trial will receive personalized therapies based on mRNA analysis and drug efficacy testing, which may include zanubrutinib. ^{6 7 8 9 10}

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 relapsed or refractory Mantle Cell Lymphoma (MCL) who have measurable disease and are willing to undergo a biopsy. They must have proper liver, kidney, heart function, and blood counts within specific ranges. Women of childbearing age must test negative for pregnancy, and men must use contraception. Exclusions include pregnant/breastfeeding women, uncontrolled medical conditions like hypertension or diabetes, certain infections like HIV or active hepatitis B, recent treatments with chemotherapy or other drugs.

Inclusion Criteria

I am able to get out of my bed or chair and move around.

My Mantle Cell Lymphoma diagnosis is confirmed with specific cell markers.

My MCL cancer has returned or didn't respond to treatment.

Exclusion Criteria

My condition is worsening quickly and I need urgent care.

I have another cancer that is more serious than my mantle cell lymphoma, with a life expectancy of 1 year or less.

Pregnant or breastfeeding females

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Biospecimen Collection

Patients undergo blood, saliva or tissue sample collection for mRNA analysis and drug efficacy testing

1-2 weeks

1 visit (in-person)

Treatment

Patients receive personalized therapies based on genetic testing results, followed every 1 cycle of therapy for 1 year

12 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, every 2 months for 1 year, every 4 months for 1 year, then every 6 months thereafter

Long-term

Bi-monthly to semi-annual visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Personalized Therapies

Trial Overview The MCL MATCH Trial aims to collect biological samples from patients with MCL to perform genetic testing. The goal is to identify personalized therapies based on the genetic mutations found in individuals whose cancer has not responded well to standard treatment options such as BTK inhibitors.

How Is the Trial Designed?

Group I: Screening (biospecimen collection) Experimental Treatment 2 Interventions

Patients undergo blood, saliva or tissue sample collection for mRNA analysis and drug efficacy testing. Patients assigned treatment per the results are followed every 1 cycle of therapy for 1 year, every 2 months for 1 year, every 4 months for 1 year then every 6 months thereafter.

Personalized Therapies is already approved in United States, China for the following indications:

Approved in United States as Brukinsa for:

• Mantle cell lymphoma (MCL) who have received at least one prior therapy
• Waldenström’s macroglobulinemia (WM)
• Relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti–CD20-based regimen
• Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)
• Relapsed or refractory follicular lymphoma (FL), in combination with obinutuzumab, after two or more lines of systemic therapy

Approved in China as Brukinsa for:

• Mantle cell lymphoma (MCL) who have received at least one prior therapy

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

Zanubrutinib, a next-generation Bruton tyrosine kinase inhibitor, shows promise as a targeted therapy for mantle cell lymphoma, particularly for patients who are elderly or have comorbidities and cannot undergo standard treatments.

An ongoing Phase III study is evaluating the safety and efficacy of zanubrutinib combined with rituximab compared to bendamustine with rituximab in patients with untreated mantle cell lymphoma who are not eligible for stem cell transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase III study of zanubrutinib plus rituximab versus bendamustine plus rituximab in transplant-ineligible, untreated mantle cell lymphoma. Dreyling, M., Tam, CS., Wang, M., et al.[2021]

Zanubrutinib, a second-generation BTK inhibitor, has shown an impressive overall response rate of 84% in treating relapsed/refractory mantle cell lymphoma (MCL) based on data from 118 patients in two clinical trials, with a duration of response lasting 14-18 months.

Despite 57% of patients experiencing significant side effects, only 8% discontinued treatment, indicating that zanubrutinib is generally well tolerated and may offer advantages over first-generation BTK inhibitors like ibrutinib due to its higher selectivity and potential for combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib: a new BTK inhibitor for treatment of relapsed/refractory mantle cell lymphoma. Weaver, AN., Jimeno, A.[2020]

In a phase II study involving 86 patients with relapsed mantle-cell lymphoma, zanubrutinib demonstrated a high overall response rate of 84%, with 68.6% achieving a complete response after a median follow-up of 18.4 months.

Zanubrutinib was generally well tolerated, with most adverse events being manageable; serious side effects like major bleeding were rare, indicating a favorable safety profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Patients with Relapsed or Refractory Mantle-Cell Lymphoma with Zanubrutinib, a Selective Inhibitor of Bruton's Tyrosine Kinase. Song, Y., Zhou, K., Zou, D., et al.[2021]

In a phase 1/2 study involving 32 patients with relapsed/refractory mantle cell lymphoma, zanubrutinib showed a high overall response rate of 84%, with 25% of patients achieving a complete response and a median duration of response of 18.5 months.

Zanubrutinib was generally well tolerated, with the most common adverse events being diarrhea (43.8%) and infections (18.8% experiencing grade ≥3 infections), indicating that while there are side effects, the treatment is effective for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib for the treatment of relapsed or refractory mantle cell lymphoma. Tam, CS., Opat, S., Simpson, D., et al.[2021]

In patients with relapsed/refractory mantle cell lymphoma (MCL) who previously failed a Bruton tyrosine kinase inhibitor, brexucabtagene autoleucel (brexu-cel) showed significantly improved overall survival compared to standard of care treatments, with hazard ratios indicating a strong survival benefit.

The analysis used multiple methods to adjust for differences in patient characteristics, consistently showing that brexu-cel led to better outcomes, highlighting its potential as an effective therapy for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indirect treatment comparison of brexucabtagene autoleucel (ZUMA-2) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma. Hess, G., Dreyling, M., Oberic, L., et al.[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]

Zanubrutinib, an oral Bruton tyrosine kinase (BTK) inhibitor, received accelerated approval in the USA on November 14, 2019, for treating adult patients with mantle cell lymphoma (MCL) who have undergone at least one prior therapy.

The approval was based on the overall response rate (ORR) observed in phase II and I/II clinical trials, highlighting its efficacy in managing B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib: First Approval. Syed, YY.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9136878/

Zanubrutinib in relapsed/refractory mantle cell lymphoma Outcomes were promising, with an overall response of 83.7%, a complete response rate of 77.9%, and no new safety concerns. At 36 months, this translates to an ...

2. brukinsahcp.com brukinsahcp.com/mcl/efficacy/

BRUKINSA® (zanubrutinib) Efficacy in MCL | HCPs The efficacy of BRUKINSA was assessed in 2 clinical trials that included a total of 118 adult patients with MCL who received at least 1 prior therapy. Tumor ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e23270

Real-world zanubrutinib treatment patterns in mantle cell ... Real-world data from across the US have demonstrated the effectiveness of zanu in MCL after treatment with another BTKi. Reasons for ...

4. tandfonline.com tandfonline.com/doi/full/10.2147/BLCTT.S426588

Zanubrutinib in Mantle Cell Lymphoma Management The median follow-up was 18.8 months. The results showed that overall response rate (ORR) was 84%, with 25% achieving complete response (CR). The median ...

5. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(24)01602-1/fulltext

MCL-509 Indirect Comparison of Efficacy of Zanubrutinib ... This STC demonstrated that zanubrutinib had significantly better PFS and OS vs acalabrutinib in the treatment of patients with R/R MCL after adjusting for a ...

6. brukinsahcp.com brukinsahcp.com/mcl/safety/

BRUKINSA® (zanubrutinib) Safety in MCL | HCPs In the (N=1550) pooled safety population, the most common adverse reactions, including laboratory abnormalities, in ≥30% of patients included neutrophil count ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/213217s007lbl.pdf

BRUKINSA (zanubrutinib) - accessdata.fda.gov Other clinically significant adverse reactions that occurred in <10% of patients with mantle cell lymphoma include major hemorrhage (defined as ≥ Grade 3 ...

8. ashpublications.org ashpublications.org/ashclinicalnews/news/6334/Long-Term-Efficacy-and-Safety-Data-From-Phase-II

Long-Term Efficacy and Safety Data From Phase II Trial ... Monotherapy with the Bruton tyrosine kinase (BTK) inhibitor zanubrutinib resulted in durable responses and an acceptable safety profile in patients with ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10683511/

Zanubrutinib in Mantle Cell Lymphoma Management The selectivity of zanubrutinib and its superior efficacy, with a well-tolerated safety profile, have proven to be attractive options for other ...

10. cancernetwork.com cancernetwork.com/view/updated-efficacy-and-safety-data-continue-to-support-zanubrutinib-use-in-released-refractory-mcl

Updated Efficacy and Safety Data Continue to Support ... Updated data from a pivotal trial that led to the approval of zanubrutinib for the treatment of patients with relapsed or refractory mantle cell lymphoma ...