Acalabrutinib for Leukemia

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Seema Bhat

Must be taking: Kinase inhibitors

Must not be taking: Steroids, CYP3A4 inhibitors, Anticoagulants, PPIs

Disqualifiers: Cardiovascular disease, Prior malignancy, 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 cycles (approximately 24 months)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called acalabrutinib to evaluate its effectiveness in treating chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The researchers aim to determine if acalabrutinib can benefit individuals with heart problems caused by another treatment, ibrutinib. Acalabrutinib blocks a protein that aids cancer cell growth. The trial seeks participants with CLL or SLL who have experienced heart issues while taking ibrutinib. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial requires that you do not take certain medications, such as strong CYP3A4 inhibitors/inducers, warfarin, and proton pump inhibitors. If you are on these, you may need to switch to alternatives or stop them before starting the trial.

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

In a previous study, acalabrutinib showed a low risk of causing heart-related side effects, even in patients with existing heart problems. Research suggests that acalabrutinib is safer for the heart compared to other treatments for chronic lymphocytic leukemia (CLL). It is also considered safe for older and more fragile patients. Overall, acalabrutinib is well-tolerated, with fewer serious side effects than some other treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for leukemia, which often include chemotherapy and various targeted therapies, acalabrutinib offers a unique approach by specifically targeting BTK (Bruton's tyrosine kinase). This mechanism of action is designed to inhibit the growth of cancer cells more precisely, potentially leading to fewer side effects compared to broader treatments like chemotherapy. Researchers are excited because acalabrutinib's targeted strategy could improve the quality of life for patients by being more effective and better tolerated.

What evidence suggests that acalabrutinib might be an effective treatment for CLL/SLL?

Research shows that acalabrutinib, the treatment under study in this trial, effectively treats chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Acalabrutinib blocks a protein called BTK, which helps stop cancer cells from growing and spreading. Studies indicate that patients with CLL who took acalabrutinib were less likely to stop treatment compared to those using ibrutinib. A review of multiple studies has also found that acalabrutinib is effective and has manageable side effects for those with CLL that has returned or is not responding to other treatments. Additionally, real-world data suggest that patients on acalabrutinib have a high overall survival rate. ^{6 7 8 9 10}

Who Is on the Research Team?

Seema A Bhat, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. It's designed for those who may have had cardiac side effects from previous treatments like ibrutinib, or are looking to start treatment that could potentially avoid such issues.

Inclusion Criteria

My white blood cell count is healthy or low due to my CLL/SLL condition.

I have been diagnosed with CLL/SLL according to the 2018 iWCLL criteria.

I have CLL and cannot tolerate ibrutinib due to heart rhythm problems.

Exclusion Criteria

I have previously been treated with acalabrutinib for the main study group or a BTK inhibitor for the pilot study.

My cancer has a C481S or PLCG2 mutation.

I have had a stem cell transplant from a donor.

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 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

24 cycles (approximately 24 months)

Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 6 months for up to 10 years.

Up to 10 years

Biannual visits

What Are the Treatments Tested in This Trial?

Interventions

• Acalabrutinib

Trial Overview The trial is testing acalabrutinib, a kinase inhibitor targeting the BTK protein on cancerous B-cells. The study will assess its effectiveness in treating CLL/SLL and its impact on heart function compared to previous therapies.

How Is the Trial Designed?

Group I: Treatment (acalabrutinib) Experimental Treatment 6 Interventions

Patients receive acalabrutinib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CMR, CT, bone marrow aspiration/biopsy, and collection of blood samples throughout the trial.

Who Is Running the Clinical Trial?

Seema Bhat

Lead Sponsor

Trials

2

Recruited

140+

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials

350

Recruited

295,000+

Acerta Pharma, LLC

Collaborator

Trials

8

Recruited

390+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40736551/

Real-world efficacy and safety outcomes of acalabrutinib in ... Real-world efficacy and safety outcomes of acalabrutinib in chronic lymphocytic leukemia: primary results of a French multicentre observational ...

2. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/5151/503709/Real-World-Effectiveness-and-Safety-Outcomes-of

Real-World Effectiveness and Safety Outcomes of ... Of the patients that progressed, the median TTNT was 4.0 months in the 1L cohort (n=33) and 4.2 months in the 2L cohort (n=31). The 18-month OS rate was 90% and ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2473952923002422

Real-world comparative effectiveness of acalabrutinib and ... Patients with CLL receiving acalabrutinib demonstrated lower rates of discontinuation and a prolonged time to discontinuation vs those receiving ibrutinib.

4. tandfonline.com tandfonline.com/doi/full/10.1080/1120009X.2024.2357980

Meta-analysis of the efficacy and adverse effects ... The results demonstrate that acalabrutinib shows efficacy in the treatment of R/R CLL with tolerable adverse reaction rates.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.01210

Acalabrutinib Versus Ibrutinib in Previously Treated ... This phase III trial prospectively compared the efficacy and safety of acalabrutinib with ibrutinib in patients with previously treated CLL to ...

6. ashpublications.org ashpublications.org/bloodneoplasia/article/2/1/100064/534858/Real-world-safety-profile-of-therapy-with

Real-world safety profile of therapy with ibrutinib or ... The ELEVATE-RR trial compared treatment with ibrutinib vs acalabrutinib in previously treated CLL, showing similar progression-free survival with both agents.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12432023/

Real-world efficacy and safety outcomes of acalabrutinib in ... The safety profile data corroborates previous findings, showing a low incidence of cardiac adverse events including for patients with pre ...

8. hematologyadvisor.com hematologyadvisor.com/news/chronic-leukemia-cll-safety-profile-acalabrutinib-superior-chemoimmunotherapy/

Safety Profile of Acalabrutinib Superior to ... The cardiovascular safety profile of acalabrutinib is superior to that of chemoimmunotherapy in treating patients with chronic lymphocytic leukemia (CLL).

9. ajmc.com ajmc.com/view/real-world-data-acalabrutinib-safety-profile-superior-in-cll-sll

Real-World Data: Acalabrutinib Safety Profile Superior in ... A new real-world analysis of patients with chronic lymphocytic leukemia (CLL) and small cell lymphocytic leukemia (SLL) indicates that the risk of adverse ...

10. targetedonc.com targetedonc.com/view/acalabrutinib-a-safe-treatment-avenue-for-older-frail-patients-with-cll

Acalabrutinib a Safe Treatment Avenue for Older, Frail ... Acalabrutinib showed a 93.5% overall response rate in older/frail CLL patients, surpassing the 65% efficacy threshold. Over half of the patients ...