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)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a drug called acalabrutinib, a type of targeted therapy, for individuals with mantle cell lymphoma who cannot tolerate ibrutinib due to side effects. The researchers aim to determine if acalabrutinib can inhibit cancer cell growth by blocking specific enzymes necessary for their development. It suits those with mantle cell lymphoma who discontinued ibrutinib not because of cancer progression, but due to severe side effects. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that acalabrutinib is likely to be safe for humans?

Research has shown that acalabrutinib is generally safe. In past studies, it caused few new health issues, particularly with high blood pressure and bleeding problems, indicating that most people tolerate it well. Its use for other conditions also enhances understanding of its safety. While no treatment is risk-free, evidence so far suggests that acalabrutinib is relatively safe for treating mantle cell lymphoma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Acalabrutinib is unique because it specifically targets Bruton's tyrosine kinase (BTK), a key protein involved in the growth and survival of Mantle Cell Lymphoma (MCL) cells. Unlike traditional chemotherapy, which can affect both healthy and cancerous cells, acalabrutinib is designed to disrupt cancer cell processes more precisely, potentially leading to fewer side effects. Researchers are excited about acalabrutinib because it offers a more targeted approach, which could improve outcomes for patients with MCL by reducing the risk of disease progression and providing a better-tolerated treatment option.

What evidence suggests that acalabrutinib might be an effective treatment for mantle cell lymphoma?

Research has shown that acalabrutinib effectively treats mantle cell lymphoma (MCL). In one study, patients with MCL that returned or didn't respond to other treatments showed promising results with acalabrutinib. Another study found that acalabrutinib helped patients live over 16 months longer without disease progression compared to those who only received chemoimmunotherapy. Additionally, real-world data from 181 patients with MCL treated with acalabrutinib demonstrated positive outcomes, supporting its potential effectiveness. These findings suggest that acalabrutinib, which participants in this trial will receive, could be a helpful treatment for people with MCL, especially for those who cannot tolerate other medications like ibrutinib. ^{1 4 5 6 7}

Who Is on the Research Team?

Preetesh Jain, MD, PHD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 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 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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7744/528340/Real-World-Effectiveness-and-Safety-Outcomes-of

Real-World Effectiveness and Safety Outcomes of ... Results: Among 181 pts with MCL treated with acala, 127 were treated in the R/R setting (study cohort) (acala monotherapy: 94 pts; combination ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10772531/

Final results and overall survival data from a phase II study ... The final results of this study demonstrated that efficacy and safety of acalabrutinib were maintained compared with data from a previous analysis (median ...

3. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/calquence-acalabrutinib-plus-chemoimmunotherapy-approved-in-the-us-for-patients-with-previously-untreated-mantle-cell-lymphoma.html

CALQUENCE® (acalabrutinib) plus chemoimmunotherapy ... Based on ECHO Phase III trial results which showed more than 16 months of progression-free survival improvement vs. chemoimmunotherapy alone.

4. onclive.com onclive.com/view/acalabrutinib-plus-br-highlights-evolving-first-line-soc-for-high-risk-mantle-cell-lymphoma

Acalabrutinib Plus BR Highlights Evolving First-Line SOC ... Martin Dreyling, MD, PhD, discusses clinical trial findings with acalabrutinib plus BR in patients with high-risk mantle cell lymphoma.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02213926

NCT02213926 | An Open-label, Phase 2 Study of ACP-196 ... The purpose of this study is to characterize the safety and efficacy profile of ACP-196 (acalabrutinib) in subjects with relapsed or refractory Mantle Cell ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6777435/

Evaluating Acalabrutinib In The Treatment Of Mantle Cell ... Acalabrutinib, a second-generation BTK inhibitor, has demonstrated impressive efficacy in clinical trials along with a safety profile that thus far appears ...

7. ema.europa.eu ema.europa.eu/en/documents/variation-report/calquence-h-c-005299-ii-0026-epar-assessment-report-extention-indication_en.pdf

Calquence - European Medicines Agency However, the observed reported events appear to be in line with acalabrutinib's known safety profile derived from RCT data. 3.6. Effects ...