Acalabrutinib for Chronic Lymphocytic Leukemia and Heart Failure

Recruiting in Palo Alto (17 mi)

+22 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: AstraZeneca

Must not be taking: Warfarin, Strong CYP3A inhibitors

Disqualifiers: Active CNS leukemia, Richter's transformation, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This will be a global Phase IV, open-label, randomised study to evaluate the safety and tolerability of acalabrutinib (monotherapy, 100 mg orally \[po\], twice daily \[bd\]) compared to investigator's choice of treatment, in patients with CLL (TN or R/R) and moderate to severe cardiac impairment. All patients will have cardiac impairment as defined by LVEF of \< 50%. Randomisation will be stratified by LVEF \> 40% vs ≤ 40% to stratify for moderate and severe cardiac impairment, which for this study are defined as follows: Severe cardiac impairment: in those with LVEF ≤ 40% Moderate cardiac impairment: in those with LVEF \> 40% to \< 50%. The study is planned to take place in approximately 20 centres globally. The study will be conducted in centres that have established close collaboration between the Haematology and Cardiology divisions, preferably with a cardio-oncologist on the team. An IDMC will be responsible for making recommendations for study continuation.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot take strong CYP3A inhibitors or inducers close to starting the study. It's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug Acalabrutinib for treating chronic lymphocytic leukemia?

Acalabrutinib has been shown to significantly extend the time patients with chronic lymphocytic leukemia live without their disease getting worse compared to standard treatments. It was effective both for patients who had never been treated before and for those whose disease returned after previous treatments. ^{1 2 3 4 5}

Is acalabrutinib safe for humans?

Acalabrutinib has been shown to be generally safe for humans, with common side effects including headache, diarrhea, and infections. Some studies noted an increased risk of heart-related issues like atrial fibrillation, but serious heart problems were not significantly higher compared to other treatments. ^{1 2 3 4 6}

How is the drug Acalabrutinib unique for treating chronic lymphocytic leukemia?

Acalabrutinib is a highly selective Bruton tyrosine kinase inhibitor, which means it specifically targets a protein that helps cancer cells grow and survive, making it more effective and with fewer side effects compared to older treatments. It has shown superior progression-free survival rates in patients with chronic lymphocytic leukemia, both in those who have never been treated before and those whose disease has returned or not responded to previous treatments. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

This trial is for adults with Chronic Lymphocytic Leukemia (CLL) who also have heart failure, specifically those with a left ventricular ejection fraction (LVEF) less than 50%. Patients must be able to take oral medication twice daily and should not have other health conditions that would interfere with the study.

Inclusion Criteria

I am 18 years old or older.

I agree to use effective birth control during and for 2 days after my last dose.

Meet the following laboratory parameters: Absolute neutrophil count (ANC) ≥ 500 cells/μL, Platelet count ≥ 30,000 cells/μL, Serum aspartate aminotransferase and ALT ≤ 3.0 × ULN, Total bilirubin ≤ 1.5 × ULN unless directly attributable to Gilbert's syndrome, Estimated creatinine clearance (eGFR using Cockcroft-Gault) ≥ 40 mL/min or serum creatinine ≤ 2 × ULN

Exclusion Criteria

I have not had major surgery in the last 30 days.

Received any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study treatment

I have not received a live virus vaccine in the last 28 days.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either acalabrutinib or investigator's choice of treatment. Each treatment cycle is 28 days/4 weeks.

32 weeks

8 visits (in-person) every 4 weeks, then every 16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment discontinuation. Safety follow-up occurs within 45 days of the last dose.

4 years

Every 16 weeks until study termination

Long-term Follow-up

Participants are contacted every 16 weeks for survival status and information on any new anti-cancer therapy until WoC, death, or study termination.

4 years

Every 16 weeks

Treatment Details

Interventions

• Acalabrutinib (Bruton's Tyrosine Kinase Inhibitor)

Trial Overview The trial is testing Acalabrutinib, taken orally twice a day, against treatments chosen by the investigator in patients with CLL and moderate to severe heart failure. The safety and tolerability of these treatments are being compared, with special attention to how they affect heart function.

Participant Groups

Group I: Treatment Arm B Experimental Treatment 1 Intervention

Patients in Arm B will receive investigator's choice of treatment its duration will be based on standard duration of therapy for that regimen or until disease progression/patient withdrawal/study termination, whichever occurs first.

Group II: Treatment Arm A (Acalabrutinib Monotherapy) Active Control 1 Intervention

All participants randomised to Arm A will receive treatment with the investigational product acalabrutinib.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Research Site Columbus, OH

Research Site Philadelphia, PA

Research Site Charlotte, NC

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4491

Patients Recruited

290,540,000+

Fortrea

Industry Sponsor

Trials

22

Patients Recruited

5,800+

eResearch Technology, Inc.

Industry Sponsor

Trials

5

Patients Recruited

1,400+

CALYX Inc.

Collaborator

Trials

1

Patients Recruited

60+

CISCRP Inc.

Collaborator

Trials

1

Patients Recruited

60+

CISCRP

Industry Sponsor

Trials

4

Patients Recruited

1,400+

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

EMA Review of Acalabrutinib for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia. [2021]

2. 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]

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. 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]

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

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

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

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