Acalabrutinib for Mantle Cell Lymphoma

Overseen By Luhua (Michael) Wang

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Warfarin, Corticosteroids, Proton-pump inhibitors, others

Disqualifiers: Pregnancy, Active hepatitis B, CNS involvement, 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

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

Compensation: Varies

Number of Visits: 4

Duration: Up to 36 cycles (each cycle is 4 weeks)

9 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot use certain medications like strong CYP3A inhibitors or inducers, warfarin, and proton-pump inhibitors. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

What data supports the effectiveness of the drug Acalabrutinib for treating Mantle Cell Lymphoma?

Acalabrutinib has been shown to be effective for treating relapsed Mantle Cell Lymphoma, with a clinical trial demonstrating an overall response rate of 81%. It is a targeted drug that works by inhibiting a specific protein involved in the growth of cancer cells. ^{1 2 3 4 5}

Is acalabrutinib safe for humans?

Acalabrutinib is generally considered safe for humans, with common side effects including headaches, which usually go away within a month, and some mild blood-related issues. Serious side effects are rare, but patients should be aware of potential interactions with other medications and consult their doctor before taking new drugs. ^{1 2 5 6 7}

What makes the drug Acalabrutinib unique for treating mantle cell lymphoma?

Acalabrutinib is a highly selective Bruton tyrosine kinase inhibitor, which means it specifically targets and blocks a protein involved in the growth of cancer cells, with minimal effects on other parts of the body. This selectivity helps reduce side effects compared to other treatments, making it a valuable option for patients with relapsed or refractory mantle cell lymphoma. ^{1 2 3 4 5}

What is the purpose of this trial?

This phase II trial studies how well acalabrutinib works in treating patients with mantle cell lymphoma that cannot tolerate ibrutinib. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Research Team

Preetesh Jain, MD, PHD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients with mantle cell lymphoma who had adverse reactions to ibrutinib. They must have resolved toxicities, acceptable blood counts, organ function within certain limits, no history of certain BTK mutations or progressive disease on ibrutinib, and not be pregnant or breastfeeding. Eligible participants should also agree to use effective contraception.

Inclusion Criteria

I have experienced severe side effects from treatment.

My blood counts meet the required levels despite having MCL in my bone marrow.

I have had severe low white blood cell counts with fever or infection.

Exclusion Criteria

I have a heart condition.

My blood pressure is not well-controlled.

I am taking more than 10 mg of prednisone or its equivalent daily.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive acalabrutinib orally twice daily on days 1-28. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.

Up to 36 cycles (each cycle is 4 weeks)

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 1 year, then annually for up to 3 years

Treatment Details

Interventions

• Acalabrutinib

Trial Overview The study tests acalabrutinib's effectiveness in treating mantle cell lymphoma in patients intolerant to ibrutinib. It examines whether acalabrutinib can halt cancer growth by inhibiting enzymes necessary for the proliferation of cancer cells.

Participant Groups

Group I: Treatment (acalabrutinib) Experimental Treatment 1 Intervention

Patients receive acalabrutinib PO BID on days 1-28. Treatment repeats every 28 days for up to 36 cycles 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+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

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, 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]

Acalabrutinib, a Bruton's tyrosine kinase inhibitor, has been shown to be effective and safe for treating chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), with significant improvements in efficacy observed in both monotherapy and combination treatments.

In clinical studies, acalabrutinib demonstrated a high rate of molecular remission when combined with venetoclax, while maintaining an acceptable safety profile, although some adverse events occurred in over 20% of patients, including myelosuppression and gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib and its use in the treatment of chronic lymphocytic leukemia. Egyed, M., Lueff, S., Borbely, J., et al.[2022]

Acalabrutinib, a selective BTK inhibitor, is effective for treating mantle cell lymphoma (MCL) in patients who have already undergone at least one therapy, with serious side effects being rare.

While common side effects like headaches are generally mild and resolve quickly, patients should be cautious about drug interactions and consult their physician before taking additional medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of acalabrutinib in patients with mantle cell lymphoma. Awan, FT., Jurczak, W.[2021]

References

1. 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]

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

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

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

Acalabrutinib for mantle cell lymphoma. [2021]

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

Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. [2021]

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

Acalabrutinib: First Global Approval. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Acalabrutinib and its use in the treatment of chronic lymphocytic leukemia. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Use of acalabrutinib in patients with mantle cell lymphoma. [2021]