Acalabrutinib vs Ibrutinib for Chronic Lymphocytic Leukemia

Not currently recruiting at 137 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Acerta Pharma BV

Must not be taking: Warfarin, Strong CYP3A inhibitors

Disqualifiers: CNS lymphoma, Richter's syndrome, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 55.2 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two treatments—acalabrutinib (also known as ACP-196) and ibrutinib—for individuals with chronic lymphocytic leukemia (CLL) who have previously received other treatments. The goal is to determine which treatment prolongs life without disease progression. Participants will take either acalabrutinib twice daily or ibrutinib once daily until the disease progresses or side effects become too severe. Suitable candidates have CLL, have undergone prior treatment, and possess certain high-risk factors, such as specific genetic changes. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants access to potentially effective treatments.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take certain drugs like strong CYP3A inhibitors/inducers or anticoagulants like warfarin within 7 days of starting the study drug.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ibrutinib has been well-studied for safety in people with chronic lymphocytic leukemia (CLL). Studies in real-world settings indicate that ibrutinib is generally safe and effective, with many patients experiencing positive results, even those at high risk due to certain genetic factors.

For acalabrutinib, less detailed safety information is available, but its stage in clinical trials indicates it has undergone several rounds of safety testing, suggesting a reasonable level of safety in earlier studies.

Both treatments have been studied extensively. Prospective trial participants should consult a healthcare provider to understand potential side effects and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about acalabrutinib for treating chronic lymphocytic leukemia (CLL) because it offers a more targeted approach compared to some existing treatments. Most CLL therapies, like ibrutinib, inhibit a protein called Bruton's tyrosine kinase (BTK) to stop cancer cell growth. However, acalabrutinib is designed to be more selective in targeting BTK, which might mean fewer side effects and better tolerability for patients. This precision could improve the quality of life for those undergoing treatment, making it a promising option in the fight against CLL.

What evidence suggests that this trial's treatments could be effective for chronic lymphocytic leukemia?

This trial will compare Acalabrutinib and Ibrutinib for treating chronic lymphocytic leukemia (CLL). Research shows that Acalabrutinib, which participants in this trial may receive, effectively treats CLL. A review of several studies found that Acalabrutinib works well for patients whose CLL has returned or not responded to other treatments, with a high success rate and manageable side effects. In one study, 92% of patients did not see their disease worsen over a year.

Ibrutinib, another treatment option in this trial, has also proven effective for CLL over the long term. Research indicates that nearly 10 years after starting treatment, patients typically went about 8.9 years without their disease worsening. After five years, 96.8% of patients responded to the treatment, with many experiencing significant improvement. Both treatments have strong evidence supporting their effectiveness, offering hope for people with CLL. ^{6 7 8 9 10}

Who Is on the Research Team?

Acerta Clinical Trials

Principal Investigator

1-888-292-9613

Are You a Good Fit for This Trial?

This trial is for adults over 18 with chronic lymphocytic leukemia (CLL) who have high-risk factors like certain genetic deletions or active disease requiring treatment. They must have had at least one prior CLL therapy, meet specific blood cell count criteria, and not be dependent on blood transfusions. People with a history of CNS leukemia, recent major surgery, or exposure to similar drugs are excluded.

Inclusion Criteria

Meet the following laboratory parameters: Absolute neutrophil count (ANC) ≥ 750 cells/μL or ≥ 500 cells/μL in participants with documented bone marrow involvement, and independent of growth factor support 7 days before assessment, Platelet count ≥ 30,000 cells/μL without transfusion support 7 days before assessment. Participants with transfusion-dependent thrombocytopenia are excluded, Serum aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤ 3.0 x upper limit of normal (ULN), Total bilirubin ≤ 1.5 x ULN, Estimated creatinine clearance ≥ 30 mL/min

I have high-risk CLL with specific genetic changes or need treatment based on certain criteria.

I can care for myself and am up and about more than 50% of my waking hours.

Exclusion Criteria

I need treatment with a strong medication that affects liver enzymes.

I have been diagnosed with CNS lymphoma or leukemia.

I have uncontrolled autoimmune blood disorders.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive either acalabrutinib or ibrutinib until disease progression or unacceptable toxicity

55.2 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

28.3 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• ACP-196
• Ibrutinib

Trial Overview The study compares the effectiveness of two drugs in treating CLL: Acalabrutinib and Ibrutinib. It focuses on which drug better prevents the disease from getting worse in patients who've already been treated before.

How Is the Trial Designed?

Group I: Acalabrutinib Experimental Treatment 1 Intervention

Participants will receive oral acalabrutinib 100 mg twice daily (BID) until disease progression (PD), or unacceptable toxicity, or other reasons for discontinuation, whichever occurs first.

Group II: Ibrutinib Active Control 1 Intervention

Participants will receive oral ibrutinib 420 mg once daily (QD) until PD, or unacceptable toxicity, or other reasons for discontinuation, whichever occurrs first.

Who Is Running the Clinical Trial?

Acerta Pharma BV

Lead Sponsor

Trials

46

Recruited

5,900+

Published Research Related to This Trial

In a study of 1,083 patients with chronic lymphocytic leukemia, those treated with acalabrutinib were 89% more likely to initiate next treatment compared to those on ibrutinib, indicating a potential difference in treatment effectiveness.

Patients on ibrutinib had a mean time to next treatment of 9.2 months, while those on acalabrutinib had a shorter mean time of 5.9 months, suggesting that acalabrutinib may lead to quicker disease progression in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time to next treatment in patients with chronic lymphocytic leukemia initiating first-line ibrutinib or acalabrutinib. Jacobs, R., Lu, X., Emond, B., et al.[2023]

In a phase III trial involving patients with previously treated chronic lymphocytic leukemia, acalabrutinib and ibrutinib showed equivalent progression-free survival rates, indicating similar efficacy in treatment.

Acalabrutinib was better tolerated by patients compared to ibrutinib, likely due to its greater selectivity, suggesting it may be a safer option for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BTK Inhibitors Show Similar Benefits in CLL. [2022]

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 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]

Ibrutinib is a targeted therapy specifically designed for treating chronic lymphocytic leukemia (CLL), which is a type of cancer that affects the blood and bone marrow.

This novel treatment works by inhibiting Bruton's tyrosine kinase (BTK), a key enzyme that helps cancer cells survive and proliferate, leading to improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. Parmar, S., Patel, K., Pinilla-Ibarz, J.[2021]

Ibrutinib is an effective treatment for chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL), showing better outcomes than traditional therapies like chlorambucil and ofatumumab in phase III trials involving elderly and previously-treated patients.

The drug has a good safety profile, although it can cause some adverse effects like bleeding and atrial fibrillation; it is recommended in treatment guidelines for patients with high-risk disease, including those with specific genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: A Review in Chronic Lymphocytic Leukaemia. Deeks, ED.[2021]

Ibrutinib is an effective oral treatment for patients with relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia (CLL), showing a 68% overall response rate in MCL and significant improvements in progression-free survival and overall survival in CLL patients, including those with specific genetic mutations.

The drug has a good safety profile, with less than 10% of patients discontinuing treatment due to adverse effects, making it a promising option for patients with various B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ibrutinib: A new drug of B-cell malignancies]. Thieblemont, C.[2021]

Citations

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

Real-world efficacy and safety outcomes of acalabrutinib in ... NAOS, a real-world study, complements these trials with real-world (rw) acalabrutinib data generated from clinical practice.

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 ... Real-world effectiveness and safety outcomes of Acalabrutinib treatment by line of therapy in patients with chronic lymphocytic leukemia and/or small ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2409804

Fixed-Duration Acalabrutinib Combinations in Untreated ... Conclusions. Acalabrutinib–venetoclax with or without obinutuzumab significantly prolonged progression-free survival as compared with ...

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. rarediseaseadvisor.com rarediseaseadvisor.com/news/acalabrutinib-improved-outcomes-high-risk-chronic-lymphocytic-leukemia/

Acalabrutinib Improved Outcomes in High-Risk CLL With a 12-month progression-free survival (PFS) rate of 92% and overall survival (OS) rate of 94%, these results underscore the utility of ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40413564/

Real-World Safety Profile of Ibrutinib in Chronic ... The overall response rate was 82.2%, with 42.2% achieving complete remission. Multivariate analysis identified age and comorbidities as ...

7. ashpublications.org ashpublications.org/bloodadvances/article/9/15/3801/537228/Real-world-survival-outcomes-in-first-line

Real-world survival outcomes in first-line ibrutinib-treated ... Among patients with CLL/SLL treated with 1L ibrutinib, similar rwOS was observed for those with or without high-risk cytogenetic features.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38342972/

Outcomes with ibrutinib in patients with chronic lymphocytic ... The REALITY study provides further evidence of the effectiveness and safety of ibrutinib in patients with CLL in a real-world setting, particularly in earlier ...

9. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/6550/501342/Real-World-Effectiveness-and-Safety-of-Ibrutinib

Real-World Effectiveness and Safety of Ibrutinib in Patients ... In this Belgian real-world study, ibrutinib was found to be an effective treatment for patients with CLL, including those with higher risk mutations, several ...

10. news.abbvie.com news.abbvie.com/2020-12-06-Combined-Data-from-Multiple-Phase-3-Studies-of-IMBRUVICA-R-ibrutinib-Show-Efficacy-and-Safety-in-High-Risk-Previously-Untreated-Chronic-Lymphocytic-Leukemia-CLL-and-Real-World-Data-Indicating-Low-Biomarker-Testing-Rates-for-These-Patients

Combined Data from Multiple Phase 3 Studies of ... First-line treatment with IMBRUVICA-based therapies resulted in sustained, long-term efficacy with high 4-year PFS rates in high-risk CLL patients.