Acalabrutinib + Rituximab for Mantle Cell Lymphoma

Overseen By Luhua (Michael) Wang

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Warfarin, Corticosteroids, CYP3A inhibitors

Disqualifiers: CNS involvement, Pregnancy, Active infection, HIV/AIDS, 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: Unknown

Duration: 24 months

53 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the side effects of acalabrutinib and rituximab and its effect in treating patients with previously untreated mantle cell lymphoma. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody that binds to a protein called CD20, which is found on B-cells, and may kill cancer cells. Giving acalabrutinib and rituximab may help to control mantle cell lymphoma in elderly patients.

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

The trial does not specify if you need to stop your current medications, but it does mention that patients on certain anticoagulants, antiplatelet, and anti-hypertensive medications are allowed. However, you cannot use warfarin, vitamin K antagonists, or strong CYP3A inhibitors or inducers. It's best to discuss your specific medications with the trial team.

Is the combination of Acalabrutinib and Rituximab safe for humans?

Acalabrutinib, used for treating certain blood cancers, has shown a generally well-tolerated safety profile, though some patients may experience side effects like low blood cell counts, fatigue, or shortness of breath. Rituximab, another cancer treatment, is also generally safe but can cause side effects such as infusion reactions and infections. Always discuss potential risks with your doctor. ^{1 2 3 4 5}

How is the drug Acalabrutinib + Rituximab unique for treating mantle cell lymphoma?

Acalabrutinib is a novel, highly selective Bruton tyrosine kinase inhibitor that has shown a high response rate in treating relapsed mantle cell lymphoma, offering a new option for patients who have not responded to other treatments. It is taken orally and is known for its improved safety profile compared to similar drugs, making it a promising choice when combined with Rituximab, which targets specific cancer cells. ^{1 2 3 5 6}

Research Team

Luhua (Michael) Wang

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for people aged 65 or older with newly diagnosed mantle cell lymphoma, which has specific biological markers. They must be able to swallow pills, have no major health issues that could interfere with the study, and not be on certain medications. Participants need normal organ function and controlled cardiovascular conditions. Pregnant women or those unable to use effective birth control are excluded.

Inclusion Criteria

I am willing to follow strict birth control measures during and after treatment.

I have a tumor that is larger than 1.5 cm, confirmed by a PET-CT scan.

My physical health has been stable for the last 2 weeks.

Exclusion Criteria

I have had a stroke in the last 6 months.

I haven't had any recent bleeding disorders or strokes.

I have had cancer before, but it was either skin cancer treated successfully, cervical or prostate cancer in situ treated successfully, or any other cancer I've been free of for 3+ years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive acalabrutinib orally twice daily and rituximab intravenously on specified days. Cycles repeat every 28 days for up to 24 months or until complete remission is achieved.

24 months

Monthly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs at 30 days, then every 4 months for 2 years, every 6 months for 2 years, and annually for 3 years.

7 years

Treatment Details

Interventions

• Acalabrutinib
• Rituximab

Trial Overview The trial is testing the combination of acalabrutinib (a drug that blocks enzymes needed for cancer cell growth) and rituximab (an antibody targeting B-cells). It aims to see how well this combo works in treating elderly patients who haven't had any previous treatments for their mantle cell lymphoma.

Participant Groups

Group I: Treatment (acalabrutinib, rituximab) Experimental Treatment 2 Interventions

Patients receive acalabrutinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab IV over 3-4 hours on days 1, 8, 15, and 22 of cycle 1, and day 1 of cycles 2-12, 14, 18, 20, 22, and 24. Cycles repeats every 28 days for up to 24 months or until complete remission is achieved in the absence of disease progression or unacceptable toxicity.

Acalabrutinib is already approved in United States, European Union for the following indications:

Approved in United States as Calquence for:

• Mantle cell lymphoma
• Chronic lymphocytic leukemia
• Small lymphocytic lymphoma

Approved in European Union as Calquence for:

• Chronic lymphocytic leukemia
• Small lymphocytic lymphoma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

In a phase 2 trial involving 124 patients with relapsed or refractory mantle cell lymphoma, acalabrutinib was associated with common treatment-related adverse events (AEs) like headache and diarrhea, but these did not lead to any treatment discontinuations.

Effective management strategies, including patient education and the use of over-the-counter medications for mild AEs, helped maintain treatment adherence and allowed for better tracking and management of nonadherence issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib: Managing Adverse Events and Improving Adherence in Patients With Mantle Cell Lymphoma. Badillo, M., Nava, D., Rosa, M., et al.[2022]

Acalabrutinib (Calquence®) has received accelerated approval from the US FDA for treating mantle cell lymphoma, based on promising results from a phase II study.

Phase III trials are currently ongoing for acalabrutinib in mantle cell lymphoma and chronic lymphocytic leukaemia, indicating its potential for broader application in treating hematological cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib: First Global Approval. Markham, A., Dhillon, S.[2018]

Acalabrutinib demonstrated significantly higher overall response rates (ORR) and complete response (CR) rates compared to other targeted therapies for relapsed/refractory mantle cell lymphoma (MCL), indicating its efficacy in treating this condition.

The safety profile of acalabrutinib was comparable or better than that of other monotherapies, although it did show increased risks of infection and anemia compared to certain combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-adjusted Indirect Comparisons of the Efficacy and Safety of Acalabrutinib Versus Other Targeted Therapies in Relapsed/Refractory Mantle Cell Lymphoma. Telford, C., Kabadi, SM., Abhyankar, S., 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]

Acalabrutinib, a Bruton tyrosine kinase inhibitor, showed a 53% overall response rate in patients with relapsed/refractory marginal zone lymphoma, indicating its efficacy in this patient population.

The treatment was generally well tolerated, with a median progression-free survival of 27.4 months and a low incidence of severe adverse events, suggesting improved safety compared to other treatments like ibrutinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2, multicentre, open-label trial (ACE-LY-003) of acalabrutinib in patients with relapsed or refractory marginal zone lymphoma. Strati, P., Coleman, M., Champion, R., et al.[2022]

Acalabrutinib, an oral Bruton tyrosine kinase inhibitor, has shown an impressive overall response rate of 81% in patients with relapsed mantle cell lymphoma (MCL), indicating its efficacy as a treatment option.

This novel therapy is not only approved for relapsed MCL but is also being tested as a first-line treatment, highlighting its potential to improve outcomes for patients with this challenging type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib for mantle cell lymphoma. Witzig, TE., Inwards, D.[2021]

References

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

Acalabrutinib: Managing Adverse Events and Improving Adherence in Patients With Mantle Cell Lymphoma. [2022]

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

Acalabrutinib: First Global Approval. [2018]

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

Matching-adjusted Indirect Comparisons of the Efficacy and Safety of Acalabrutinib Versus Other Targeted Therapies in Relapsed/Refractory Mantle Cell Lymphoma. [2021]

4. England pubmed.ncbi.nlm.nih.gov

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

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

A phase 2, multicentre, open-label trial (ACE-LY-003) of acalabrutinib in patients with relapsed or refractory marginal zone lymphoma. [2022]

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

Acalabrutinib for mantle cell lymphoma. [2021]