Acalabrutinib for Chronic Lymphocytic Leukemia

Not currently recruiting at 23 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Acerta Pharma BV

Must not be taking: BCL-2 inhibitors, CYP3A inhibitors

Disqualifiers: Prior malignancy, Cardiovascular disease, Gastrointestinal issues, 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: Up to 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called acalabrutinib for individuals with chronic lymphocytic leukemia (CLL) who did not respond well to a previous medication, ibrutinib. The researchers aim to assess the effectiveness and safety of acalabrutinib for those whose CLL worsened after stopping ibrutinib. This trial may suit individuals diagnosed with CLL who have tried at least one other treatment and experienced issues with ibrutinib. Participants must be able to swallow capsules without difficulty and be prepared for all study procedures. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking any systemic anticancer therapy for CLL between stopping ibrutinib and enrolling in the trial. If you are on a strong CYP3A inhibitor, you cannot participate in the trial.

Is there any evidence suggesting that ACP-196 (acalabrutinib) is likely to be safe for humans?

In earlier studies, acalabrutinib has proven safe for people with chronic lymphocytic leukemia (CLL). Research suggests that acalabrutinib usually causes fewer heart-related side effects than a similar treatment called ibrutinib, making it a potentially safer option for those with heart concerns.

One study found that patients with relapsed CLL tolerated acalabrutinib well, experiencing fewer severe side effects compared to traditional chemotherapy. Real-world evidence also supports that acalabrutinib carries a lower risk of side effects in people with CLL.

Overall, these findings indicate that acalabrutinib is well-tolerated in humans, with fewer serious side effects, especially when compared to some other treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Acalabrutinib is unique because it targets a specific enzyme called Bruton's tyrosine kinase (BTK) that plays a crucial role in the growth of cancer cells in chronic lymphocytic leukemia (CLL). Unlike standard treatments like chemotherapy or other BTK inhibitors that may have broader effects on the body, acalabrutinib is designed to be more selective, potentially reducing side effects. Researchers are excited about this treatment because its targeted approach may offer patients a more effective and tolerable option compared to existing therapies.

What evidence suggests that acalabrutinib might be an effective treatment for chronic lymphocytic leukemia?

Research has shown that acalabrutinib, the treatment under study in this trial, effectively treats chronic lymphocytic leukemia (CLL), particularly in patients unresponsive to other treatments. Studies have found that 95% of patients experienced either a reduction in cancer size or a halt in its growth. In real-world settings, 85% of patients who had previously tried other treatments remained alive 18 months after starting acalabrutinib. This suggests that acalabrutinib can be a promising option for those with relapsed or hard-to-treat CLL. ^{3 6 7 8 9}

Who Is on the Research Team?

Acerta Clinical Trials

Principal Investigator

1-888-292-9613; [e-mail]

Are You a Good Fit for This Trial?

This trial is for adults with Chronic Lymphocytic Leukemia (CLL) who've had at least one prior treatment and can't tolerate Ibrutinib. They should have progressed after stopping Ibrutinib, be able to swallow capsules, and have a decent performance status. Exclusions include other cancers within 2 years, significant gut surgery or diseases affecting absorption, active infections including HIV/Hepatitis B/C, recent major surgery or heart issues, bleeding disorders, certain drug interactions, previous BCL-2 inhibitor use like Venetoclax.

Inclusion Criteria

I have had at least one treatment for chronic lymphocytic leukemia.

Intolerant of ibrutinib

Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty

Exclusion Criteria

Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening

I have HIV, hepatitis B or C, or another uncontrolled infection.

I have not had a stroke or brain bleed in the last 2 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ACP-196 (acalabrutinib) 100 mg orally twice a day

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• ACP-196 (acalabrutinib)

Trial Overview The study tests Acalabrutinib's effectiveness and safety in patients with relapsed/refractory CLL intolerant to Ibrutinib therapy. It's a Phase 2 trial focusing on those who didn't respond well to their previous treatments.

How Is the Trial Designed?

Group I: ACP-196 (acalabrutinib) Experimental Treatment 1 Intervention

ACP-196 (acalabrutinib) 100 mg to be administered orally (PO) twice a day BID

Who Is Running the Clinical Trial?

Acerta Pharma BV

Lead Sponsor

Trials

46

Recruited

5,900+

Published Research Related to This Trial

Acalabrutinib, a selective BTK inhibitor, has been FDA approved for treating chronic lymphocytic leukemia (CLL) and shows improved efficacy and safety compared to standard treatments, including ibrutinib.

In multinational phase 1/2 and phase 3 studies, acalabrutinib demonstrated significant effectiveness in treatment-naïve and relapsed refractory CLL patients, with fewer treatment-limiting toxicities such as atrial fibrillation and bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib and Its Therapeutic Potential in the Treatment of Chronic Lymphocytic Leukemia: A Short Review on Emerging Data. Isaac, K., Mato, AR.[2020]

Acalabrutinib has been approved in the EU for treating both treatment-naïve and relapsed/refractory chronic lymphocytic leukemia (CLL), showing significant improvements in progression-free survival compared to standard therapies in two phase III trials involving adult patients.

The safety profile of acalabrutinib is generally acceptable, with common side effects including headache, diarrhea, and infections, and the overall benefit-risk ratio is considered positive for its use in CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMA Review of Acalabrutinib for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia. Delgado, J., Josephson, F., Camarero, J., et al.[2021]

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 Bruton's tyrosine kinase inhibitor, was found to increase the risk of any-grade cardiac events in patients with chronic lymphocytic leukemia, with a risk ratio of 1.75.

There was a notable trend indicating a higher risk of any-grade atrial fibrillation associated with acalabrutinib, with a risk ratio of 2.56, although no significant increase in hypertension or high-grade cardiac events was observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib-Related Cardiac Toxicities in Patients with Chronic Lymphocytic Leukemia: A Meta-Analysis of Randomized Controlled Trials. Htut, TW., Han, MM., Thein, KZ.[2022]

In a phase III study involving 310 patients with relapsed/refractory chronic lymphocytic leukemia (CLL), acalabrutinib monotherapy significantly improved progression-free survival (PFS) compared to investigator's choice treatments, with a median PFS not reached for acalabrutinib versus 16.5 months for the comparator group.

Acalabrutinib demonstrated a favorable safety profile, with serious adverse events occurring in 29% of patients, compared to 56% for idelalisib plus rituximab and 26% for bendamustine plus rituximab, indicating it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. Ghia, P., Pluta, A., Wach, M., et al.[2021]

In a phase 3 study involving 535 patients with treatment-naive chronic lymphocytic leukaemia, acalabrutinib combined with obinutuzumab or as a monotherapy significantly improved progression-free survival compared to the standard treatment of obinutuzumab with chlorambucil, with median survival not reached for the acalabrutinib groups versus 22.6 months for the chlorambucil group.

The safety profile of acalabrutinib was favorable, with fewer infusion reactions and a lower incidence of grade 3 or higher adverse events compared to the obinutuzumab-chlorambucil group, indicating it is a viable chemotherapy-free treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Sharman, JP., Egyed, M., Jurczak, W., et al.[2021]

In a pivotal phase 3 study with 310 patients, acalabrutinib significantly improved progression-free survival (PFS) compared to standard treatments (Idelalisib plus rituximab or bendamustine plus rituximab), with a median PFS not reached for acalabrutinib versus 16.8 months for IdR/BR.

After approximately 4 years of follow-up, acalabrutinib demonstrated a favorable safety profile, with lower rates of treatment discontinuation due to adverse events compared to IdR/BR, while maintaining similar rates of serious infections and other significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib Versus Investigator's Choice in Relapsed/Refractory Chronic Lymphocytic Leukemia: Final ASCEND Trial Results. Ghia, P., Pluta, A., Wach, M., et al.[2022]

Acalabrutinib, a selective Bruton tyrosine kinase inhibitor, showed improved safety outcomes compared to other targeted therapies for treatment-naïve chronic lymphocytic leukemia (CLL) patients, although it was associated with a higher risk of neutropenia and leukopenia in some cases.

The analysis indicated that acalabrutinib (with or without obinutuzumab) had similar efficacy in terms of progression-free survival compared to other treatments, suggesting it is a safe and effective option for CLL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-adjusted indirect comparisons of safety and efficacy of acalabrutinib versus other targeted therapies in patients with treatment-naïve chronic lymphocytic leukemia. Davids, MS., Telford, C., Abhyankar, S., et al.[2021]

Citations

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

Real-world efficacy and safety outcomes of acalabrutinib in ... NAOS, one of the largest real-world cohorts of acalabrutinib-treated CLL patients in Europe, showed effectiveness and safety consistent with ...

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 ... The 18-month OS rate was 90% and 85% for the 1L and 2L+ cohorts, respectively ( Figure 2). After initiation of acalabrutinib treatment, the ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1509981

Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic ... At a median follow-up of 14.3 months, the overall response rate was 95%, including 85% with a partial response and 10% with a partial response ...

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

Meta-analysis of the efficacy and adverse effects ... Literature to date has shown acalabrutinib has a high overall response rate (ORR), including in CLL patients with high-risk disease. The ORR for ...

5. cureus.com cureus.com/articles/297472-assessment-of-the-efficacy-and-safety-of-acalabrutinib-in-chronic-lymphocytic-leukemia-cll-a-systematic-review-and-metaanalysis

Assessment of the Efficacy and Safety of Acalabrutinib ... Acalabrutinib is an effective treatment for CLL, demonstrating significant clinical benefits in terms of response rates and PFS. The current ...

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/PMC10644206/

Detailed safety profile of acalabrutinib vs ibrutinib in ... Key Points. •. Acalabrutinib has a favorable benefit-risk profile, including lower incidence of cardiovascular-related toxicities, vs ibrutinib.

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 ...