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

Trial Summary

What is the purpose of this trial?

This clinical trial collects and tests samples using genetic testing to find personalized treatments that may work best for patients with mantle cell lymphoma (MCL) that has come back (relapsed) or does not respond to treatment (refractory). Several types of MCL are difficult to treat due to specific genetic changes (mutations or alterations in the DNA/RNA expression in the cells) that make them not respond to a certain type of drug called a Bruton's tyrosine kinase (BTK) inhibitor. The goal of this clinical research study is to use genetic testing to identify which drugs may be most effective in treating patients with MCL who have this type of genetic mutation.

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 data supports the idea that Personalized Therapy for Mantle Cell Lymphoma (also known as: Personalized Therapies, Zanubrutinib, Brukinsa) is an effective drug?

The available research shows that zanubrutinib, a drug used in personalized therapy for mantle cell lymphoma, has been effective in treating this condition. In one study, zanubrutinib showed a high response rate of 84% in patients with relapsed or refractory mantle cell lymphoma, meaning that most patients responded well to the treatment. Additionally, the drug was approved by the FDA based on these positive results. Compared to other treatments, zanubrutinib has fewer unwanted side effects and is better tolerated, which means patients are more likely to continue using it. This makes it a promising option for those who have not responded to other treatments. ^{1 2 3 4 5}

What safety data is available for zanubrutinib in treating mantle cell lymphoma?

Zanubrutinib, a Bruton tyrosine kinase inhibitor, has been evaluated in several studies for its safety and efficacy in treating mantle cell lymphoma (MCL). It received accelerated FDA approval in 2019 for relapsed/refractory MCL based on a high overall response rate. In clinical trials, zanubrutinib showed a well-tolerated safety profile with common adverse events including diarrhea, contusion, constipation, and upper respiratory tract infections. Grade 3 or higher adverse events were reported in 59.4% of patients, with anemia, pneumonia, and myalgia being the most common. Despite these side effects, only a small percentage of patients discontinued treatment, indicating that zanubrutinib is generally well tolerated. ^{1 4 5 6 7}

Is the drug Zanubrutinib (also known as Brukinsa) a promising treatment for Mantle Cell Lymphoma?

Yes, Zanubrutinib is a promising drug for Mantle Cell Lymphoma. It has shown high response rates and is well-tolerated, making it a good option for patients who have already tried other treatments. It is especially useful for those who cannot undergo standard treatments or stem cell transplants. ^{1 2 4 5 6}

Research Team

Luhua (Michael) Wang

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

References

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

A Phase III study of zanubrutinib plus rituximab versus bendamustine plus rituximab in transplant-ineligible, untreated mantle cell lymphoma. [2021]

2. United States 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. [2021]

3. United States 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. [2023]

4. Spain pubmed.ncbi.nlm.nih.gov

Zanubrutinib: a new BTK inhibitor for treatment of relapsed/refractory mantle cell lymphoma. [2020]

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

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

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

Zanubrutinib: First Approval. [2020]

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

Zanubrutinib for the treatment of relapsed or refractory mantle cell lymphoma. [2021]