Acalabrutinib for Lymphoma

Recruiting at 1 trial location

Overseen By Amanda Spearman

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: BTK inhibitors, Strong CYP3A4 inhibitors

Disqualifiers: Active systemic disease, Uncontrolled illness, Cardiovascular disease, HIV, 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

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

Compensation: Varies

Number of Visits: 16

Duration: Up to 2 years

49 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing Acalabrutinib, a drug used in other cancers, to see if it can help people with a type of brain cancer that hasn't responded to other treatments. The drug works by stopping the cancer cells from growing.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you require treatment with strong CYP3A4 inhibitors/inducers or anticoagulation with warfarin. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Acalabrutinib for treating lymphoma?

Acalabrutinib has shown effectiveness in treating certain types of blood cancers, like chronic lymphocytic leukemia (CLL) and mantle cell lymphoma, by significantly delaying disease progression and having a favorable safety profile compared to other treatments. In a study for marginal zone lymphoma, it also showed a good response rate, with many patients experiencing tumor reduction. ^{1 2 3 4 5}

Is Acalabrutinib safe for humans?

Acalabrutinib is generally considered safe for humans, with most side effects being mild to moderate, such as headache and diarrhea. However, there is a higher risk of some heart-related issues, like atrial fibrillation (irregular heartbeat), but serious heart problems are not significantly increased. ^{2 5 6 7 8}

What makes the drug Acalabrutinib unique for treating lymphoma?

Acalabrutinib is a second-generation Bruton tyrosine kinase inhibitor that is highly selective and potent, which means it targets the cancer cells more precisely with fewer side effects compared to older drugs like ibrutinib. This makes it a promising option for treating certain types of lymphoma, such as mantle cell lymphoma, with a better safety profile. ^{5 8 9 10 11}

Research Team

Lakshmi Nayak

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

Adults with recurrent or refractory central nervous system lymphoma (CNSL) who have had at least one prior CNS-directed therapy can join this trial. They must be able to understand and sign consent, have a life expectancy over 3 months, an ECOG Performance Status of 0-1, and meet specific health criteria like adequate blood counts and organ function. Pregnant women, those unable to swallow pills or with certain infections or bleeding disorders cannot participate.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

Participant must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care

Participant must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study

Exclusion Criteria

Participants unable to undergo MRI brain

My high blood pressure is not controlled despite taking medication.

I haven't had cancer treatment or been in a trial within the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Acalabrutinib in a dose-escalation study to determine safety and efficacy

Up to 2 years

Regular visits every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Follow-up visits every 8 weeks

Treatment Details

Interventions

• Acalabrutinib

Trial Overview The trial is testing the safety and effectiveness of Acalabrutinib for people whose CNSL has come back after treatment or didn't respond to previous treatments. It's in phases 1/2 which means they're starting to see how well it works and what doses are safe.

Participant Groups

Group I: Acalabrutinib Dose Expansion Experimental Treatment 1 Intervention

Phase 2 Participants will receive Acalabrutinib at the pre-determined dosage established in Phase 1.

Group II: Acalabrutinib Dose Escalation Experimental Treatment 1 Intervention

Phase 1 Dose escalation will occur using a 3+3 dose escalation approach, evaluating three separate dose levels. * Acalabrutinib 200mg 2x daily * Acalabrutinib 300mg 2x daily * Acalabrutinib 400mg 2x 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?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

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]

Acalabrutinib, a Bruton tyrosine kinase inhibitor, showed a 53% overall response rate in patients with relapsed/refractory marginal zone lymphoma, indicating its efficacy in this patient population.

The treatment was generally well tolerated, with a median progression-free survival of 27.4 months and a low incidence of severe adverse events, suggesting improved safety compared to other treatments like ibrutinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2, multicentre, open-label trial (ACE-LY-003) of acalabrutinib in patients with relapsed or refractory marginal zone lymphoma. Strati, P., Coleman, M., Champion, R., et al.[2022]

In a phase 2 trial involving 124 patients with relapsed or refractory mantle cell lymphoma, acalabrutinib was associated with common treatment-related adverse events (AEs) like headache and diarrhea, but these did not lead to any treatment discontinuations.

Effective management strategies, including patient education and the use of over-the-counter medications for mild AEs, helped maintain treatment adherence and allowed for better tracking and management of nonadherence issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib: Managing Adverse Events and Improving Adherence in Patients With Mantle Cell Lymphoma. Badillo, M., Nava, D., Rosa, 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 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 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 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 is an effective treatment option for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), but it can cause unique adverse events and toxicities that need careful management.

Nurses play a crucial role in improving patient outcomes by educating patients about potential side effects, monitoring for clinical symptoms, and ensuring adherence to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib: Nursing Considerations for Use in Patients With Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma. Nierman, P.[2022]

Acalabrutinib, a second-generation BTK inhibitor, was shown to effectively inhibit BTK activity and cell proliferation in canine lymphoma cells, indicating its potential efficacy in treating B-cell malignancies.

In a clinical trial with 20 dogs, acalabrutinib was generally well tolerated, with a 25% overall response rate and a median progression-free survival of 22.5 days, suggesting it is a safe treatment option for canine B-cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of the Novel BTK Inhibitor Acalabrutinib in Canine Models of B-Cell Non-Hodgkin Lymphoma. Harrington, BK., Gardner, HL., Izumi, R., et al.[2018]

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

A phase 2, multicentre, open-label trial (ACE-LY-003) of acalabrutinib in patients with relapsed or refractory marginal zone lymphoma. [2022]

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

Acalabrutinib: Managing Adverse Events and Improving Adherence in Patients With Mantle Cell Lymphoma. [2022]

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

Acalabrutinib in treatment-naive chronic lymphocytic leukemia. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

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

9. 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]

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

Acalabrutinib: Nursing Considerations for Use in Patients With Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma. [2022]

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

Preclinical Evaluation of the Novel BTK Inhibitor Acalabrutinib in Canine Models of B-Cell Non-Hodgkin Lymphoma. [2018]