Acalabrutinib for Chronic Lymphocytic Leukemia and Heart Failure

Recruiting at 25 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: AstraZeneca

Must not be taking: Warfarin, Strong CYP3A inhibitors

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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

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: 41

Duration: 32 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess the safety and tolerability of acalabrutinib, a medication for people with chronic lymphocytic leukemia (CLL) who also have moderate to severe heart issues. Participants will receive either acalabrutinib or a treatment chosen by their doctor. Good candidates for this trial are those with CLL and heart problems who need treatment.

As a Phase 4 trial, this research helps to understand how the already FDA-approved and effective treatment benefits more patients.

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 is the safety track record for acalabrutinib?

Research has shown that acalabrutinib is generally safe for patients with chronic lymphocytic leukemia (CLL), including those with heart conditions. Studies have found that heart-related issues are rare with acalabrutinib, even in individuals with pre-existing heart problems. This treatment is, in fact, safer for the heart than traditional cancer treatments like chemoimmunotherapy.

Real-world data from Europe also support these findings, showing consistent safety results for acalabrutinib in CLL patients. Overall, acalabrutinib presents a low risk of causing heart problems, making it a relatively safe option for managing CLL, especially for those with heart concerns. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Acalabrutinib is unique because it specifically targets the Bruton's tyrosine kinase (BTK) enzyme, which plays a crucial role in the growth of chronic lymphocytic leukemia (CLL) cells. Unlike other treatments for CLL, which may have broader effects on the immune system, acalabrutinib offers a more precise approach by directly interfering with the signaling pathways that cancer cells rely on. Researchers are excited about acalabrutinib because it has shown promise in providing effective treatment while potentially reducing some of the side effects associated with traditional chemotherapy options. This targeted action could mean fewer complications and a better quality of life for patients.

What evidence suggests that acalabrutinib might be an effective treatment for chronic lymphocytic leukemia with heart failure?

Research has shown that acalabrutinib effectively treats chronic lymphocytic leukemia (CLL). In the ELEVATE-TN trial, it reduced the risk of disease progression or death by up to 90%, significantly lowering the chance of cancer worsening. Participants in Treatment Arm A of this trial will receive acalabrutinib monotherapy. Acalabrutinib also causes fewer heart-related side effects, which benefits patients with heart issues. Compared to similar treatments, fewer patients discontinue its use due to side effects. Overall, acalabrutinib is a strong option for managing CLL, particularly for those concerned about heart safety. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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

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

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

I have had no more than 2 treatments for my CLL.

Exclusion Criteria

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

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Acalabrutinib

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.

How Is the Trial Designed?

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.

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?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Fortrea

Industry Sponsor

Trials

22

Recruited

5,800+

eResearch Technology, Inc.

Industry Sponsor

Trials

5

Recruited

1,400+

CALYX Inc.

Collaborator

Trials

1

Recruited

60+

CISCRP Inc.

Collaborator

Trials

1

Recruited

60+

CISCRP

Industry Sponsor

Trials

4

Recruited

1,400+

Published Research Related to This Trial

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12012573/

Cumulative review of cardiac failure with acalabrutinib in ... Cumulative review of cardiac failure with acalabrutinib in the treatment of chronic lymphocytic leukemia using data from clinical trials and ...

2. ajmc.com ajmc.com/view/acalabrutinib-shows-low-cardiac-toxicity-in-clinical-real-world-data

Acalabrutinib Shows Low Cardiac Toxicity in Clinical, Real- ... Acalabrutinib demonstrates a favorable cardiovascular safety profile in CLL, with low cardiac failure rates compared to ibrutinib and ...

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

Real-world efficacy and safety outcomes of acalabrutinib in ... In the ELEVATE-TN trial, acalabrutinib with or without obinutuzumab significantly reduced the risk of disease progression or death by 90% and by ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2152265025001508

Cardiac Events in Three Phase 3 Randomized Trials ... Cardiac events were infrequent with acalabrutinib relative to comparator treatment. This trend was consistent in patients with or without CV disorders at ...

5. ashpublications.org ashpublications.org/bloodadvances/article/7/16/4291/495767/Real-world-comparative-effectiveness-of

Real-world comparative effectiveness of acalabrutinib and ... In the largest available study comparing BTKis, patients with CLL receiving acalabrutinib demonstrated lower rates of discontinuation and a ...

6. hematologyadvisor.com hematologyadvisor.com/news/chronic-leukemia-cll-safety-profile-acalabrutinib-superior-chemoimmunotherapy/

Safety Profile of Acalabrutinib Superior to ... The cardiovascular safety profile of acalabrutinib is superior to that of chemoimmunotherapy in treating patients with chronic lymphocytic leukemia (CLL).

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04008706

NCT04008706 | Acalabrutinib Safety Study in Untreated ... To evaluate the safety and tolerability of acalabrutinib monotherapy in participants with treatment-naïve or relapsed/refractory chronic lymphocytic leukemia.