Acalabrutinib + BR for Mantle Cell Lymphoma

Not currently recruiting at 237 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 65+

Sex: Any

Trial Phase: Phase 3

Sponsor: Acerta Pharma BV

Disqualifiers: Cardiovascular disease, Malabsorption, Infections, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 6 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for people with mantle cell lymphoma, a type of blood cancer. The study compares the effectiveness of adding acalabrutinib, a targeted cancer therapy, to the standard treatments of bendamustine and rituximab, against using a placebo with those standard treatments. The main goal is to determine if this new combination works better for patients who have not received any prior systemic cancer treatments. Individuals diagnosed with mantle cell lymphoma who have not yet undergone treatment may be a good fit for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to access potentially groundbreaking treatment.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that combining acalabrutinib with bendamustine and rituximab is safe for patients with mantle cell lymphoma. Research indicates that patients generally tolerate this combination well. While some side effects occur, they are usually manageable. Most patients handle the treatment without serious problems. The FDA has approved this combination for mantle cell lymphoma, indicating confidence in its safety. ^{1 2 3 4 5}

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

Researchers are excited about Acalabrutinib in combination with bendamustine and rituximab for treating Mantle Cell Lymphoma because it targets a specific protein, Bruton's tyrosine kinase (BTK), which plays a crucial role in the growth of cancer cells. Unlike traditional chemotherapy, which affects both healthy and cancerous cells, Acalabrutinib offers a more targeted approach, potentially leading to fewer side effects. Additionally, this treatment is administered orally, which can be more convenient than intravenous options. This innovative approach could offer a promising alternative to current standards like ibrutinib, particularly for patients seeking targeted therapy with potentially improved tolerability.

What evidence suggests that this trial's treatments could be effective for mantle cell lymphoma?

In this trial, participants will receive either acalabrutinib combined with bendamustine and rituximab or a placebo combined with bendamustine and rituximab. Research has shown that acalabrutinib with bendamustine and rituximab effectively treats mantle cell lymphoma. Acalabrutinib blocks a protein that aids cancer cell growth. Studies have found this combination to be less harmful and more effective than using similar drugs alone. The FDA has approved this combination for patients not yet treated for mantle cell lymphoma, highlighting its strong potential. This makes it a promising option for those dealing with this type of cancer. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for men and women aged 65 or older with untreated mantle cell lymphoma (MCL) confirmed by specific genetic markers. Participants must be relatively active and healthy, as indicated by an ECOG performance status of ≤2, and agree to use effective contraception. Those with significant gastrointestinal issues, uncontrolled infections, recent heart problems, or a long QT interval on ECG are excluded.

Inclusion Criteria

I am 65 years old or older.

My Mantle Cell Lymphoma needs treatment and I haven't received any systemic anticancer therapies before.

I agree to use effective birth control during and up to 12 months after the study.

Exclusion Criteria

I do not have serious heart problems or recent heart attacks.

I do not have any significant issues with my digestive system that could affect medication absorption.

Concurrent participation in another therapeutic clinical trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive acalabrutinib or placebo in combination with bendamustine and rituximab. Cycles are repeated every 28 days.

Up to 6 years

Monthly cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 years

What Are the Treatments Tested in This Trial?

Interventions

• Acalabrutinib
• Bendamustine
• Placebo
• Rituximab

Trial Overview The study tests the effectiveness of acalabrutinib combined with bendamustine and rituximab (BR) against a placebo plus BR in patients who have not previously been treated for MCL. The goal is to see if adding acalabrutinib improves treatment outcomes compared to the standard BR therapy alone.

How Is the Trial Designed?

Group I: Acalabrutinib in combination with bendamustine and rituximab Experimental Treatment 3 Interventions

Acalabrutinib administered twice per day (BID) orally (PO) plus bendamustine on Days 1 and 2 and rituximab on Day 1; cycles are repeated every 28 days.

Group II: Placebo in combination with bendamustine and rituximab Placebo Group 3 Interventions

Matching placebo administered BID PO plus bendamustine on Days 1 and 2 and rituximab on Day 1; cycles are repeated every 28 days.

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?

Acerta Pharma BV

Lead Sponsor

Trials

46

Recruited

5,900+

AstraZeneca

Industry 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

Published Research Related to This Trial

The RBAC500 regimen, which combines rituximab, bendamustine, and low-dose cytarabine, showed a high efficacy in treating elderly patients with mantle cell lymphoma, with 91% of patients achieving a complete response after treatment.

While the treatment did not meet the predefined safety criteria due to manageable hematological toxicities, such as neutropenia and thrombocytopenia, it was deemed effective and safe enough to warrant further investigation in phase 3 trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab, bendamustine, and low-dose cytarabine as induction therapy in elderly patients with mantle cell lymphoma: a multicentre, phase 2 trial from Fondazione Italiana Linfomi. Visco, C., Chiappella, A., Nassi, L., et al.[2018]

Acalabrutinib (Calquence®) has received accelerated approval from the US FDA for treating mantle cell lymphoma, based on promising results from a phase II study.

Phase III trials are currently ongoing for acalabrutinib in mantle cell lymphoma and chronic lymphocytic leukaemia, indicating its potential for broader application in treating hematological cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib: First Global Approval. Markham, A., Dhillon, S.[2018]

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]

The combination of bendamustine and rituximab (BR) showed a high overall response rate of 90% in 63 patients with mantle cell or low-grade lymphomas, with a complete remission rate of 60%.

The median progression-free survival was 24 months, indicating that BR is an effective treatment option for patients in their first to third relapse or refractory to previous treatments, although myelosuppression was noted as a significant side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine plus rituximab is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade non-Hodgkin's lymphoma. Rummel, MJ., Al-Batran, SE., Kim, SZ., et al.[2022]

Acalabrutinib demonstrated significantly higher overall response rates (ORR) and complete response (CR) rates compared to other targeted therapies for relapsed/refractory mantle cell lymphoma (MCL), indicating its efficacy in treating this condition.

The safety profile of acalabrutinib was comparable or better than that of other monotherapies, although it did show increased risks of infection and anemia compared to certain combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-adjusted Indirect Comparisons of the Efficacy and Safety of Acalabrutinib Versus Other Targeted Therapies in Relapsed/Refractory Mantle Cell Lymphoma. Telford, C., Kabadi, SM., Abhyankar, S., et al.[2021]

Zanubrutinib, a next-generation Bruton tyrosine kinase inhibitor, shows promise as a targeted therapy for mantle cell lymphoma, particularly for patients who are elderly or have comorbidities and cannot undergo standard treatments.

An ongoing Phase III study is evaluating the safety and efficacy of zanubrutinib combined with rituximab compared to bendamustine with rituximab in patients with untreated mantle cell lymphoma who are not eligible for stem cell transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase III study of zanubrutinib plus rituximab versus bendamustine plus rituximab in transplant-ineligible, untreated mantle cell lymphoma. Dreyling, M., Tam, CS., Wang, M., et al.[2021]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00690

Acalabrutinib Plus Bendamustine-Rituximab in Untreated ... The combination of the Bruton tyrosine kinase inhibitor ibrutinib with bendamustine-rituximab for first-line treatment of mantle cell lymphoma (MCL) prolonged ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40311141/

Acalabrutinib Plus Bendamustine-Rituximab in Untreated ... Acalabrutinib was shown to be efficacious and less toxic than ibrutinib in a head-to-head trial in chronic lymphocytic leukemia and therefore ...

3. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-acalabrutinib-bendamustine-and-rituximab-previously-untreated-mantle-cell-lymphoma

FDA approves acalabrutinib with bendamustine and ... FDA approves acalabrutinib with bendamustine and rituximab for previously untreated mantle cell lymphoma · Efficacy and Safety · Expedited ...

4. onclive.com onclive.com/view/acalabrutinib-plus-br-highlights-evolving-first-line-soc-for-high-risk-mantle-cell-lymphoma

Acalabrutinib Plus BR Highlights Evolving First-Line SOC ... Martin Dreyling, MD, PhD, discusses clinical trial findings with acalabrutinib plus BR in patients with high-risk mantle cell lymphoma.

5. haematologica.org haematologica.org/article/view/haematol.2023.284896

Safety and efficacy of acalabrutinib plus bendamustine and ... Results indicate that ABR was safe and efficacious, supporting further study in patients with TN MCL. Introduction. Mantle cell lymphoma (MCL) ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39234862/

Safety and efficacy of acalabrutinib plus bendamustine and ... Results indicate that ABR was safe and efficacious, supporting further study in patients with TN MCL. Publication types. Clinical Trial, Phase I ...

7. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/calquence-acalabrutinib-plus-chemoimmunotherapy-approved-in-the-us-for-patients-with-previously-untreated-mantle-cell-lymphoma.html

CALQUENCE® (acalabrutinib) plus chemoimmunotherapy ... Results from the ECHO trial showed CALQUENCE plus bendamustine and rituximab reduced the risk of disease progression or death by 27 ...