Acalabrutinib vs Standard Therapy for Chronic Lymphocytic Leukemia

Not currently recruiting at 183 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare the effectiveness of acalabrutinib, a new targeted therapy, against standard therapies for individuals with chronic lymphocytic leukemia (CLL) who have previously received treatment. Participants will receive either acalabrutinib alone or a combination of rituximab (an antibody therapy) with either idelalisib or bendamustine. The goal is to determine which approach better manages CLL. Ideal candidates are those previously treated for CLL and experiencing active symptoms such as significant weight loss, fatigue, or night sweats. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Previous studies have shown that acalabrutinib is well-tolerated. In a large group of 1,029 patients, common side effects included anemia (low red blood cell count), neutropenia (low white blood cell count), and upper respiratory tract infections, affecting more than 30% of patients. However, these side effects are generally manageable. Research also shows that acalabrutinib is safer for the heart compared to some other chemotherapy treatments for chronic lymphocytic leukemia (CLL).

Rituximab, idelalisib, and bendamustine are standard treatments for CLL, and their safety profiles are well-known. Rituximab can cause reactions during infusion, idelalisib may lead to liver problems and diarrhea, and bendamustine might cause low blood cell counts. While these side effects are known, doctors are experienced in managing them.

Overall, acalabrutinib and the other treatments have been widely studied for safety, and doctors are prepared to handle the usual side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for CLL?

Acalabrutinib is unique because it specifically targets Bruton's tyrosine kinase (BTK), a key enzyme that helps cancer cells grow and survive in chronic lymphocytic leukemia (CLL). Most standard treatments for CLL, like Rituximab or Bendamustine, don't target BTK directly, which makes Acalabrutinib stand out as it may offer a more precise approach with potentially fewer side effects. Researchers are excited about Acalabrutinib because it could provide a more effective treatment option with a better safety profile than current therapies.

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

Research has shown that acalabrutinib, which participants in this trial may receive, effectively treats chronic lymphocytic leukemia (CLL). One study found that 83% of people taking acalabrutinib did not experience cancer growth or spread, compared to 56% of those on a different treatment. This suggests that acalabrutinib effectively controls CLL.

In this trial, another treatment arm combines rituximab with either idelalisib or bendamustine. Studies have demonstrated that these combinations help patients live longer without disease progression and improve overall survival for those with relapsed CLL. These findings support using these options as effective treatments for managing CLL. ^{2 3 6 7 8}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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, 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]

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. calquence.com calquence.com/why-calquence/how-effective-calquence-cll.html

How Effective Is CALQUENCE® (acalabrutinib)? | CLL 83% (128 of 155) of people on CALQUENCE had no cancer growth or spread compared to 56% (87 of 155) of people taking an alternative combination treatment.§.

4. 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 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6029555/

Efficacy of bendamustine and rituximab as first salvage ... We performed an observational study on the efficacy of ben-damustine and rituximab (BR) as first salvage regimen in chronic lymphocytic leukemia (CLL).

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/216387Orig2s000Correctedlbl.pdf

CALQUENCE® (acalabrutinib) tablets, for oral use In this pooled safety population, adverse reactions in ≥ 30% of 1029 patients were anemia, neutropenia, upper respiratory tract infection, ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04008706

NCT04008706 | Acalabrutinib Safety Study in Untreated ... To evaluate the safety and tolerability of acalabrutinib monotherapy in participants with treatment-naïve or relapsed/refractory chronic lymphocytic leukemia.

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).