Acalabrutinib for Chronic Lymphocytic Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Acerta Pharma BV

Must not be taking: Steroids

Disqualifiers: Richter's transformation, Impaired hepatic function, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests acalabrutinib, a new treatment for individuals with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Researchers aim to evaluate patient responses to acalabrutinib by using two different dosing schedules. The trial suits those with CLL or SLL who experience symptoms such as significant weight loss, extreme tiredness, or night sweats. Participants should be prepared to follow study procedures, including taking capsules and undergoing tests. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but it does exclude those who have had certain treatments like chemotherapy or radiotherapy in the last 4 weeks. It's best to discuss your specific medications with the trial team.

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

Research has shown that acalabrutinib is generally well-tolerated by patients with chronic lymphocytic leukemia (CLL). Studies have found it to be safer than traditional chemoimmunotherapy, potentially causing fewer serious side effects. In a large European study, many patients experienced positive outcomes with acalabrutinib, and its safety aligned with earlier research findings. These results suggest that acalabrutinib could offer a safer treatment option for people with CLL, providing effective care with a lower risk of severe side effects. ^{1 2 3 4 5}

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

Acalabrutinib is unique because it targets a protein called Bruton's tyrosine kinase (BTK), which plays a crucial role in the survival and growth of cancer cells in chronic lymphocytic leukemia (CLL). Unlike traditional chemoimmunotherapy treatments like FCR (fludarabine, cyclophosphamide, and rituximab) or ibrutinib, acalabrutinib offers a more selective inhibition of BTK. This selectivity may lead to fewer side effects and better tolerability for patients. Researchers are excited about acalabrutinib because it has the potential to provide effective treatment with an improved safety profile, allowing patients to manage CLL with less impact on their quality of life.

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

Research has shown that acalabrutinib effectively treats chronic lymphocytic leukemia (CLL). One study found that 83% of people taking acalabrutinib experienced no cancer growth or spread, compared to 56% of those on other treatments. Another study reported that 95% of patients responded to the treatment, with many showing partial improvement. Real-world data also support these findings, indicating that acalabrutinib provides significant benefits. This trial will evaluate two dosing regimens of acalabrutinib, and these studies suggest that acalabrutinib can be a strong option for managing CLL. ^{1 2 6 7 8}

Who Is on the Research Team?

AstraZeneca Clinical Study Information Center

Principal Investigator

1-877-240-9479 - [e-mail]

Are You a Good Fit for This Trial?

Adults with chronic lymphocytic leukemia or small lymphocytic lymphoma, specifically those who have relapsed/refractory disease or are treatment-naive with certain genetic mutations (17p deletion, TP53, NOTCH1). Participants must experience significant symptoms like weight loss, fevers without infection, night sweats, fatigue, enlarged spleen/lymph nodes or rapid increase in white blood cells. They should be able to swallow capsules and undergo biopsies.

Inclusion Criteria

I am 18 or older with a confirmed diagnosis.

Active disease as defined by at least one of the following (IWCLL consensus criteria): Weight loss ≥10% within the previous 6 months, Extreme fatigue, Fevers of greater than 100.5ºF for ≥2 weeks without evidence of infection, Night sweats for more than one month without evidence of infection, Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia, Massive or progressive splenomegaly, Massive nodes or clusters or progressive lymphadenopathy, Progressive lymphocytosis with an increase of >50% over a 2 month period, or an anticipated doubling time of less than 6 months, Compensated autoimmune hemolysis, Relapsed/Refractory CLL or treatment naïve CLL patients with 17p deletion, TP53 mutation, or NOTCH1 mutation, Agreement to use acceptable methods of contraception during the study and for 30 days after the last dose of study drug if sexually active and able to bear or beget children, Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty and serial biopsies, Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations)

Exclusion Criteria

My condition has transformed into a more aggressive form of cancer.

My liver isn't working properly.

I haven't had cancer treatments or experimental drugs in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive acalabrutinib in one of two dosing regimens for CLL/SLL

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Acalabrutinib

Trial Overview The trial is testing Acalabrutinib's effectiveness for two groups of patients: those who have previously been treated for CLL/SLL and those who haven't. The goal is to see how well the drug works in controlling the disease across different patient backgrounds.

How Is the Trial Designed?

Group I: Arm B Experimental Treatment 2 Interventions

Subjects will be randomized to receive 1 of 2 dosing regimens: 1) acalabrutinib, dose A once daily; or 2) acalabrutinib, dose B twice daily.

Group II: Arm A Experimental Treatment 2 Interventions

Subjects will be randomized to receive 1 of 2 dosing regimens: 1) acalabrutinib, dose A once daily; or 2) acalabrutinib, dose B twice daily.

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+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

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 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]

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 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 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 demonstrated a high overall response rate of 97% in treatment-naive patients with chronic lymphocytic leukemia (CLL), with a median follow-up of 53 months, indicating its strong efficacy as a monotherapy.

The treatment was generally safe, with serious adverse events reported in 38% of patients, but only 6% discontinued due to adverse effects, suggesting that acalabrutinib can be a durable and manageable option for patients with CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib in treatment-naive chronic lymphocytic leukemia. Byrd, JC., Woyach, JA., Furman, RR., et al.[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]

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, 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/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 ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39463596/

Assessment of the Efficacy and Safety of Acalabrutinib in ... Acalabrutinib is an active drug in treating CLL that induces significant clinical benefits concerning response rates and PFS.

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

Safety Profile of Acalabrutinib Superior to ... Results of the study showed a significantly lower risk of mortality in the acalabrutinib treatment group compared with the chemoimmunotherapy ...

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

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