Acalabrutinib for Lymphoma

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Lakshmi Nayak

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

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

Breakthrough Therapy

Approved in 2 Jurisdictions

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.

Trial 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 (Bruton's Tyrosine Kinase (BTK) Inhibitor)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Dana Farber Cancer Institute Boston, MA

Brigham and Women's Hospital Boston, MA

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1128

Patients Recruited

382,000+

Findings from Research

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]

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]

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]

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]

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]

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]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib in treatment-naive chronic lymphocytic leukemia. Byrd, JC., Woyach, JA., Furman, RR., et al.[2022]

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]

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]