Acalabrutinib for Chronic Lymphocytic Leukemia

(ASSURE Trial)

No longer recruiting at 129 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Proton-pump inhibitors, Warfarin

Disqualifiers: Prior malignancy, Cardiovascular disease, Hepatitis, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 1

Duration: 48 cycles (approximately 48 months)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of acalabrutinib, a medication for chronic lymphocytic leukemia (CLL), a type of blood cancer. The study includes three groups: those who have never received treatment, those whose cancer has returned or didn't respond to previous treatment, and those who have tried a specific previous medication called ibrutinib. People with active CLL symptoms, such as frequent fatigue or night sweats, and without certain other medical issues, might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking proton-pump inhibitors and certain anticoagulants like warfarin at least 7 days before starting the study. If you're on these medications, you may need to switch to alternatives like H2-receptor antagonists or antacids.

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

Research shows that acalabrutinib is generally safe for people with chronic lymphocytic leukemia (CLL). Studies have found that patients taking acalabrutinib had a lower risk of death compared to those using traditional chemoimmunotherapy treatments. Most people tolerate this medication well. Common side effects include headache and diarrhea, but these are usually mild.

In real-world use, outside strict clinical trials, acalabrutinib has proven effective, and its safety has remained consistent. This indicates it works well and is generally safe for many patients. While side effects can occur, they are usually manageable. Patients should always discuss any concerns with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chronic lymphocytic leukemia?

Acalabrutinib is unique because it specifically targets Bruton's tyrosine kinase (BTK), a key player in the growth and survival of cancer cells in chronic lymphocytic leukemia (CLL). Unlike other treatments that may affect multiple pathways, acalabrutinib offers a more focused approach, potentially leading to fewer side effects. This precision targeting is what excites researchers, as it holds promise for improved outcomes and quality of life for patients with CLL, especially those who have relapsed or are refractory to other treatments like ibrutinib.

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

Studies have shown that acalabrutinib works well in treating chronic lymphocytic leukemia (CLL). One study found that 95% of patients experienced a reduction in cancer symptoms. Another study reported that 83% of people taking acalabrutinib had no cancer growth or spread, compared to 56% with another treatment. These findings suggest that acalabrutinib can control the disease better than some other treatments. Real-world evidence also supports its effectiveness in treating CLL, offering significant benefits for patients. Participants in this trial will join different cohorts to further evaluate acalabrutinib's effectiveness in various CLL scenarios. ^{1 2 6 7 8}

Who Is on the Research Team?

Adel Habib, MD

Principal Investigator

AstraZeneca

Dr. Carsten Niemann, MD

Principal Investigator

Rigshospitalet, Denmark

Are You a Good Fit for This Trial?

This trial is for adults with chronic lymphocytic leukemia (CLL) who are either untreated, have relapsed or are refractory to previous treatments, or have had prior ibrutinib therapy. Participants must show signs of progressive disease and meet specific blood cell count criteria. Pregnant women, individuals with recent malignancies other than CLL, those on certain medications like proton-pump inhibitors or strong CYP3A inhibitors/inducers, and patients with significant heart issues cannot join.

Inclusion Criteria

My blood test shows a specific type of abnormal B-cells.

My blood tests show worsening anemia or low platelets.

I have very large (over 10 cm), growing, or bothersome swollen lymph nodes.

Exclusion Criteria

Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening.

I have had cancer before, but I've been cancer-free for over 2 years, except for minor skin cancers or early prostate cancer.

My kidney function, measured by creatinine clearance, is below 30 mL/min.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive acalabrutinib 100 mg twice daily for up to 48 cycles (each cycle is 28 days)

48 cycles (approximately 48 months)

In-clinic visits every cycle for Cycles 1-6, every 3 cycles for Cycles 7-12, and every 3 cycles with assessments every 6 cycles for Cycles 13-48

Safety Follow-up

Safety follow-up visits occur approximately 30 days from the last dose of study treatment

Approximately 1 month

Disease Follow-up

Participants who continue to derive benefit from treatment after 48 cycles will be followed every 24 weeks until study intervention discontinuation

Varies by participant

What Are the Treatments Tested in This Trial?

Interventions

• Acalabrutinib

Trial Overview

The study tests the safety and effectiveness of acalabrutinib taken twice daily in three groups: treatment-naive patients, those whose CLL has returned or didn't respond to past treatments, and patients previously treated with ibrutinib. The trial will last about six years including a two-year recruitment phase followed by up to four years of treatment cycles.

How Is the Trial Designed?

Group I: Acalabrutinib Experimental Treatment 1 Intervention

Participants will be enrolled into 3 cohorts. In the treatment-naive cohort, a minimum of 300 participants with treatment-naïve chronic lymphocytic leukemia will be enrolled. In the relapsed/refractory cohort, approximately 200 participants with relapsed/refractory chronic lymphocytic leukemia will be enrolled. In the prior ibrutinib cohort, approximately 40 participants with Prior ibrutinib therapy will be enrolled.

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

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40736551/

Real-world efficacy and safety outcomes of acalabrutinib in ...

NAOS, a real-world study, complements these trials with real-world (rw) acalabrutinib data generated from clinical practice.

2.

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 ...

Real-world effectiveness and safety outcomes of Acalabrutinib treatment by line of therapy in patients with chronic lymphocytic leukemia and/or small ...

3.

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.§.

4.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1509981

Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic ...

At a median follow-up of 14.3 months, the overall response rate was 95%, including 85% with a partial response and 10% with a partial response ...

5.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39463596/

Assessment of the Efficacy and Safety of Acalabrutinib in ...

Acalabrutinib is an active drug in treating CLL that induces significant clinical benefits concerning response rates and PFS.

6.

hematologyadvisor.com

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

Safety Profile of Acalabrutinib Superior to ...

Results of the study showed a significantly lower risk of mortality in the acalabrutinib treatment group compared with the chemoimmunotherapy ...

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.

8.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2409804

Fixed-Duration Acalabrutinib Combinations in Untreated ...

Acalabrutinib–venetoclax with or without obinutuzumab significantly prolonged progression-free survival as compared with chemoimmunotherapy in fit patients ...