Acalabrutinib vs Standard Therapy for Chronic Lymphocytic Leukemia

Recruiting at 151 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Acerta Pharma BV

Must not be taking: BCL-2 inhibitors, BCR inhibitors, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 22 months

310 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you require certain medications like strong CYP3A inhibitors/inducers or proton-pump inhibitors. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Acalabrutinib for treating chronic lymphocytic leukemia?

Acalabrutinib has been shown to significantly extend the time patients live without their disease getting worse compared to standard treatments in multiple studies. It was approved in the EU and the US for both newly diagnosed and previously treated patients with chronic lymphocytic leukemia, demonstrating a favorable balance between benefits and side effects. ^{1 2 3 4 5}

Is acalabrutinib safe for humans?

Acalabrutinib is generally considered safe for humans, with common side effects including headache, diarrhea, and infections. Some patients may experience more serious side effects like neutropenia (low white blood cell count) and atrial fibrillation (irregular heartbeat), but these are less common. ^{2 3 5 6 7}

How does the drug Acalabrutinib differ from standard treatments for chronic lymphocytic leukemia?

Acalabrutinib is a highly selective Bruton tyrosine kinase inhibitor that offers improved efficacy and tolerability compared to standard treatments like idelalisib plus rituximab or bendamustine plus rituximab. It is designed to be more selective than similar drugs, reducing some side effects like atrial fibrillation and bleeding, and it can be taken orally, which is convenient for patients. ^{2 3 4 5 8}

What is the purpose of this trial?

This trial compares acalabrutinib with rituximab combined with either idelalisib or bendamustine in patients with chronic lymphocytic leukemia who have already been treated before. Acalabrutinib stops cancer cells from growing, while rituximab helps the immune system kill them. Idelalisib blocks growth signals, and bendamustine damages cancer cell DNA. Acalabrutinib has been approved for the treatment of mantle cell lymphoma and chronic lymphocytic leukemia in the US.

Research Team

Acerta Clinical Trials

Principal Investigator

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

Eligibility Criteria

This trial is for adults with chronic lymphocytic leukemia (CLL) who have had at least one prior treatment. Participants must have a certain level of physical fitness (ECOG 0-2), not be pregnant or breastfeeding, agree to use effective contraception, and meet specific blood disease criteria without severe other health issues like heart disease or uncontrolled infections.

Inclusion Criteria

My condition requires treatment according to specific leukemia criteria.

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

I agree not to donate sperm during the trial.

Exclusion Criteria

I have or am suspected to have Richter's syndrome or prolymphocytic leukemia.

I have not had previous treatments with radio- or toxin-conjugated antibodies.

I am on blood thinners like warfarin.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Acalabrutinib monotherapy or Rituximab in combination with Idelalisib or Bendamustine

22 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

53 months

Treatment Details

Interventions

• Acalabrutinib
• Bendamustine
• Idelalisib
• Rituximab

Trial Overview The study compares the effectiveness of acalabrutinib against two combinations: rituximab with idelalisib or bendamustine in people with previously treated CLL. It aims to determine which treatment works better for managing this type of leukemia.

Participant Groups

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

Acalabrutinib (ACP-196) Monotherapy

Group II: Rituximab Plus Idelalisib or Bendamustine Active Control 3 Interventions

Investigator's Choice of Rituximab Plus Idelalisib or Bendamustine

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?

Acerta Pharma BV

Lead Sponsor

Trials

46

Recruited

5,900+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Spain pubmed.ncbi.nlm.nih.gov

An update on acalabrutinib to treat chronic lymphocytic leukemia. [2021]

2. England pubmed.ncbi.nlm.nih.gov

EMA Review of Acalabrutinib for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia. [2021]

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

Acalabrutinib Versus Investigator's Choice in Relapsed/Refractory Chronic Lymphocytic Leukemia: Final ASCEND Trial Results. [2022]

4. United States 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. [2021]

5. United States 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. [2021]

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

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

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

Acalabrutinib-Related Cardiac Toxicities in Patients with Chronic Lymphocytic Leukemia: A Meta-Analysis of Randomized Controlled Trials. [2022]

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

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