Acalabrutinib + ACP-319 for Chronic Lymphocytic Leukemia

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Acerta Pharma BV

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

Trial Summary

What is the purpose of this trial?

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)

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).

What data supports the effectiveness of the drug Acalabrutinib for treating Chronic Lymphocytic Leukemia?

Research shows that Acalabrutinib, a drug that targets a specific protein involved in cancer cell growth, is effective in treating Chronic Lymphocytic Leukemia (CLL). It has been shown to significantly delay disease progression compared to standard treatments, with a favorable safety profile, making it a promising option for both newly diagnosed and previously treated CLL patients. ^{1 2 3 4 5}

Is the combination of Acalabrutinib and ACP-319 safe for treating chronic lymphocytic leukemia?

Acalabrutinib, used alone or with other drugs, generally has a good safety profile for treating chronic lymphocytic leukemia, with common side effects including headache, diarrhea, and infections. However, there is a higher risk of certain heart-related issues and blood cell count changes. The overall safety is considered acceptable, and the benefits outweigh the risks. ^{1 2 3 6 7}

How is the drug Acalabrutinib + ACP-319 unique for treating chronic lymphocytic leukemia?

Acalabrutinib is a highly selective Bruton tyrosine kinase inhibitor, which means it specifically targets a protein involved in the growth and survival of cancer cells, making it different from other treatments that may affect more parts of the body. It has shown a favorable safety profile compared to other targeted therapies, with fewer side effects, while maintaining similar effectiveness in delaying disease progression. ^{1 2 3 4 8}

Research Team

Acerta Clinical Trials

Principal Investigator

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

Eligibility Criteria

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.

I will start the study drug after waiting 5 half-lives since my last chemotherapy or experimental therapy.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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'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 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 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]

References

1. 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]

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

ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. [2021]

4. England 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. [2021]

5. 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]

6. 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]

7. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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