Acalabrutinib + ACP-319 for Chronic Lymphocytic Leukemia

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Acerta Pharma BV

Must not be taking: Immunotherapy, Corticosteroids

Disqualifiers: Significant cardiovascular disease, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 60 cycles of 28 days

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, acalabrutinib (a type of targeted therapy) and ACP-319, to determine their safety and effectiveness in treating chronic lymphocytic leukemia (CLL), a type of blood cancer. Researchers aim to discover if these drugs together can benefit individuals whose CLL has returned or not responded to previous treatments. Participants should have CLL that has relapsed or resisted at least one prior treatment and should not have any serious heart issues or other significant health problems. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you cannot participate if you are on ongoing immunosuppressive therapy or have had recent chemotherapy or experimental therapy without a sufficient washout period (time without taking certain medications).

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

Research has shown that acalabrutinib is usually well-tolerated by people with chronic lymphocytic leukemia (CLL). Studies have found it to be safer than traditional chemoimmunotherapy, with fewer serious side effects. Most patients experience manageable side effects.

Less information is available about ACP-319. However, it is being tested with acalabrutinib in studies for treating CLL. The current trial is in an early phase, so researchers are closely monitoring safety. This stage of research focuses on understanding the safety of these drugs when used together, making it important to watch for any new information. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about acalabrutinib and ACP-319 for treating Chronic Lymphocytic Leukemia (CLL) because they offer a fresh approach compared to standard treatments like chemoimmunotherapy or Bruton’s tyrosine kinase (BTK) inhibitors. Acalabrutinib is a next-generation BTK inhibitor that is designed to be more selective, potentially reducing side effects seen with other BTK inhibitors. ACP-319 works as a PI3K delta inhibitor, aiming to block a different pathway crucial for cancer cell survival. By combining these two targeted therapies, there's hope for a more effective strategy with a better safety profile for CLL patients.

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

Research has shown that acalabrutinib effectively treats chronic lymphocytic leukemia (CLL). One study found that 92% of patients taking acalabrutinib with immunotherapy experienced no cancer growth, compared to 47% of those on chemoimmunotherapy. Another study reported a 95% overall response rate, with most patients experiencing partial remission. In this trial, participants will initially receive either acalabrutinib or ACP-319, followed by a combination of both treatments. Animal studies demonstrated that combining ACP-319 with acalabrutinib led to better tumor control, suggesting potential benefits for humans as well. These findings indicate that both treatments could effectively manage CLL. ^{1 2 5 6 7}

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?

Adults over 18 with chronic lymphocytic leukemia (CLL) that has come back or didn't respond to at least one treatment can join this trial. Those with certain genetic changes in their CLL may qualify after just one prior treatment. Participants must be able to perform daily activities with relative ease, agree to use birth control, and not have other serious health issues or recent treatments that could affect the study.

Inclusion Criteria

I am over 18 and my CLL has not improved after at least one treatment, or it came back.

I can take care of myself and am up and about more than half of my waking hours.

Agreement to use contraception during the study and for 30 days after the last dose of study drugs if sexually active and able to bear or beget children.

Exclusion Criteria

History of prior allogeneic bone marrow progenitor cell or solid organ transplantation.

I do not have a severe illness that could risk my safety in the study.

Creatinine > 1.5 x institutional upper limit of normal (ULN); total bilirubin > 1.5 x ULN (unless due to Gilbert's disease); and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN unless disease related.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ACP-319 or acalabrutinib for 7 days, then both drugs in combination

60 cycles of 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Acalabrutinib
• ACP-319

Trial Overview The trial is testing a combination of two drugs, acalabrutinib and ACP-319, for treating CLL. It aims to find out how safe this combo is and how well it works against the disease.

How Is the Trial Designed?

Group I: acalabrutinib Experimental Treatment 2 Interventions

Starts with acalabrutinib for 7 days, then combined with ACP-319 afterwards.

Group II: ACP-319 Experimental Treatment 2 Interventions

Starts with ACP-319 for 7 days, then combined with acalabrutinib afterwards.

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 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'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]

Acalabrutinib, a selective BTK inhibitor, has shown improved progression-free survival in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) compared to standard treatments, indicating its efficacy as a treatment option.

The safety profile of acalabrutinib is favorable, with most side effects being mild (grade 1/2), such as headache and diarrhea, and a low rate of treatment discontinuation due to adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib: A Selective Bruton Tyrosine Kinase Inhibitor for the Treatment of B-Cell Malignancies. Abbas, HA., Wierda, WG.[2023]

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 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 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 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. clinicaltrials.gov clinicaltrials.gov/study/NCT02157324

Acalabrutinib in Combination With ACP-319, for Treatment ... This study is evaluating the safety and efficacy of the combined use of acalabrutinib and ACP-319, for the treatment of chronic lymphocytic leukemia (CLL).

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

Real-world efficacy and safety outcomes of acalabrutinib in ... Real-world efficacy and safety outcomes of acalabrutinib in chronic lymphocytic leukemia: primary results of a French multicentre observational ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5626587/

Combined BTK and PI3Kδ inhibition with acalabrutinib ... We here demonstrate for the first time that the combination of acalabrutinib and ACP-319 provided more potent tumor control in vivo, significantly extending the ...

4. ashpublications.org ashpublications.org/bloodadvances/article/8/13/3345/515785/Acalabrutinib-based-regimens-in-frontline-or

Acalabrutinib-based regimens in frontline or relapsed ... Overall, our results demonstrate the long-term benefit of acalabrutinib-based regimens in patients with CLL and higher-risk genomic features, regardless of line ...

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

Meta-analysis of the efficacy and adverse effects ... The ORR for acalabrutinib in relapsed/refractory (R/R) CLL has been documented from 76% to 95% with a complete response (CR) rate ranging from 3 ...

6. clinicaltrial.be clinicaltrial.be/en/details/11811?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

Acalabrutinib in Combination With ACP-319, for Treatment... A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.15_suppl.7518

Acalabrutinib combined with PI3Kδ inhibitor ACP-319 in ... ... chronic lymphocytic leukemia (CLL): ASCEND final results. Paolo Ghia ... Long-term safety with ≥12 months of pirtobrutinib in relapsed ...