Acalabrutinib for Lymphoma

Recruiting at 2 trial locations

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, Acalabrutinib, to determine its safety and effectiveness for individuals with central nervous system lymphoma (CNSL) that has recurred or resisted other treatments. Initially, the study will explore different doses to identify the optimal amount, then test that dose on additional participants. Individuals with a history of CNS lymphoma who have tried at least one other treatment may qualify for this trial. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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.

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

Studies have shown that Acalabrutinib is generally well-tolerated by people with relapsed or refractory mantle cell lymphoma. In a study with 181 patients, most experienced only mild side effects when taking Acalabrutinib alone or with other treatments. Common side effects included headache and diarrhea, while serious side effects were less common.

Another study followed patients for over three years and found that the treatment was safe for long-term use. These findings suggest that Acalabrutinib could be a safe option for people with certain types of lymphoma. However, this trial specifically focuses on its use for central nervous system lymphoma, which is a different condition. Discuss potential risks and benefits with the trial team before joining. ^{1 2 3 4 5}

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

Acalabrutinib is unique because it specifically targets Bruton's tyrosine kinase (BTK), a protein crucial for the growth and survival of lymphoma cells. Unlike traditional chemotherapy, which can affect both cancerous and healthy cells, acalabrutinib offers a more targeted approach, potentially reducing side effects. Researchers are excited about this treatment because its precise mechanism allows for potentially better outcomes with fewer adverse effects, offering hope for improved quality of life for patients with lymphoma.

What evidence suggests that Acalabrutinib might be an effective treatment for CNSL?

Research has shown that Acalabrutinib may help treat certain types of lymphoma. In studies with patients who have mantle cell lymphoma, 83% experienced no cancer growth or spread while taking Acalabrutinib, compared to 56% on another treatment. Additionally, when combined with other treatments, Acalabrutinib reduced the risk of disease progression by 27% compared to standard treatments. These results suggest that Acalabrutinib could be effective for hard-to-treat lymphomas, such as central nervous system lymphoma (CNSL). This trial will evaluate Acalabrutinib through a dose escalation phase to determine the optimal dosage, followed by a dose expansion phase to further assess its effectiveness. Although more research is needed, these findings offer hope for its potential effectiveness. ^{1 3 5 6 7}

Who Is on the Research Team?

Lakshmi Nayak

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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

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

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 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 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 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]

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 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]

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 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]

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]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7744/528340/Real-World-Effectiveness-and-Safety-Outcomes-of

Real-World Effectiveness and Safety Outcomes of ... Results: Among 181 pts with MCL treated with acala, 127 were treated in the R/R setting (study cohort) (acala monotherapy: 94 pts; combination ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10772531/

Final results and overall survival data from a phase II study ... Acalabrutinib also demonstrated efficacy in patients with blastoid/pleomorphic morphology, high-risk MIPI score, and Ki-67 index >30% and >50%, which are poor ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124105708

Real-World Effectiveness and Safety Outcomes of ... Results: Among 181 pts with MCL treated with acala, 127 were treated in the R/R setting (study cohort) (acala monotherapy: 94 pts; combination ...

4. 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.

5. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2024/calquence-acalabrutinib-plus-chemoimmunotherapy-reduced-the-risk-of-disease-progression-or-death-by-27-percentage-vs-standard-of-care-in-patients-with-untreated-mantle-cell-lymphoma-in-echo-phase-iii-trial.html

CALQUENCE® (acalabrutinib) plus chemoimmunotherapy ... Results showed the CALQUENCE combination regimen reduced the risk of disease progression or death by 27% compared to standard-of-care chemoimmunotherapy.

6. 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 ... Results: A total of 530 patients were identified and included in the analysis. Of these patients, 63% (n=334) received 1L acalabrutinib and 37% ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12432023/

Real-world efficacy and safety outcomes of acalabrutinib in ... The estimated 48-month progression-free survival (PFS) rates after 4 years of follow-up were 87.0% for acalabrutinib-obinutuzumab, 77.9% for ...