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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the effectiveness of combining two drugs, acalabrutinib (a type of targeted therapy) and rituximab (a monoclonal antibody), in treating mantle cell lymphoma, a type of blood cancer. Researchers seek to discover if these drugs can inhibit cancer cell growth and help control the disease. The trial is recruiting elderly patients (65 and older) diagnosed with mantle cell lymphoma who have not yet received treatment. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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 there any evidence suggesting that acalabrutinib and rituximab are likely to be safe for humans?

Research shows that the combination of acalabrutinib and rituximab is generally well-tolerated by patients with mantle cell lymphoma. Studies have found that common side effects include low red blood cell count (anemia), low white blood cell count (neutropenia), and upper respiratory infections, occurring in more than 30% of patients.

Acalabrutinib blocks certain enzymes that help cancer cells grow, while rituximab targets a protein on B-cells to help kill the cancer cells. This combination has been studied before, and while some side effects are common, they are often manageable. Rituximab is already approved by the FDA for other uses, indicating that its safety is well-understood.

Clinical trial participants receive close monitoring to manage any side effects. Those considering participation should discuss potential risks and benefits with a healthcare provider for more personal insight. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of acalabrutinib and rituximab for treating Mantle Cell Lymphoma because of its unique approach. While standard treatments often rely on traditional chemotherapy, acalabrutinib is a next-generation Bruton's tyrosine kinase (BTK) inhibitor that specifically targets cancer cells, potentially reducing side effects. When paired with rituximab, an antibody that marks cancer cells for destruction by the immune system, this combo could offer a powerful one-two punch against the disease. This targeted strategy might provide a more effective and tolerable treatment option compared to existing therapies.

What evidence suggests that acalabrutinib and rituximab might be effective for mantle cell lymphoma?

Participants in this trial will receive a combination of acalabrutinib and rituximab, which research has shown to be very effective for treating mantle cell lymphoma, especially in older adults. Acalabrutinib stops enzymes that help cancer cells grow, while rituximab targets and destroys cancerous B-cells. Studies have found that this combination can safely lead to significant reductions in cancer, sometimes making it undetectable. Patients in earlier research managed their lymphoma well without needing traditional chemotherapy. This treatment not only reduces cancer cells but also alters the immune system to better fight the disease. ^{1 2 4 5 6}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04765111

Acalabrutinib and Rituximab for the Treatment of ... This phase II trial studies the side effects of acalabrutinib and rituximab and its effect in treating patients with previously untreated mantle cell lymphoma.

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/747/530365/Acalabrutinib-and-Rituximab-in-Elderly-Patients

Acalabrutinib and Rituximab in Elderly Patients with Newly ... Acalabrutinib with Rituximab Is Highly Effective First Line Treatment for Older Patients with Mantle Cell Lymphoma. Preetesh Jain, Chi Young ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00690

Acalabrutinib Plus Bendamustine-Rituximab in Untreated ... The combination of the Bruton tyrosine kinase inhibitor ibrutinib with bendamustine-rituximab for first-line treatment of mantle cell lymphoma (MCL) prolonged ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124057902

Acalabrutinib with Rituximab Is Highly Effective First Line ... Chemotherapy-free frontline therapy with AR is highly effective, safe, induces deep MRD negative responses and alters immune landscape in older pts with MCL.

5. haematologica.org haematologica.org/article/view/haematol.2023.284896

Safety and efficacy of acalabrutinib plus bendamustine and ... Results indicate that ABR was safe and efficacious, supporting further study in patients with TN MCL. Introduction. Mantle cell lymphoma (MCL) ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/216387s004lbl.pdf

Clinical Trials - accessdata.fda.gov In this pooled safety population, adverse reactions in ≥ 30% of 1029 patients were anemia, neutropenia, upper respiratory tract infection, thrombocytopenia, ...