Acalabrutinib + BR/VR for Mantle Cell Lymphoma

Not currently recruiting at 28 trial locations

Overseen By Acerta Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Acerta Pharma BV

Disqualifiers: Cardiovascular disease, Malabsorption syndrome, Infections, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Duration not specified

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the combination of new and existing drugs to treat mantle cell lymphoma, a rare blood cancer. The focus is on testing the safety and effectiveness of acalabrutinib (a targeted therapy) with other drugs, such as bendamustine, rituximab, and venetoclax, in different patient groups. Some participants have not received any previous treatment, while others have experienced relapses. People with untreated mantle cell lymphoma who need treatment might be suitable for this study. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this combination therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the trial is for treatment-naive patients, it suggests that participants should not have been treated with prior therapies for Mantle Cell Lymphoma.

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

Research has shown that the combination of acalabrutinib, bendamustine, and rituximab is generally well-tolerated by patients with mantle cell lymphoma. Many patients did not experience severe side effects during follow-up. The FDA has approved this combination for some patients, indicating its safety.

Research also shows promising results for the combination of acalabrutinib, venetoclax, and rituximab. One study found that many patients responded well to this treatment without serious side effects. While some patients experienced side effects, they were usually manageable.

Overall, these treatments have good safety records based on current research. Joining a trial could provide access to advanced treatments with supportive safety data. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for mantle cell lymphoma because they combine acalabrutinib with other potent drugs like bendamustine, rituximab, and venetoclax to potentially enhance effectiveness. Acalabrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor that specifically targets and disrupts cancer cell signaling pathways, which is different from standard chemotherapy approaches that attack rapidly dividing cells in general. This targeted action may not only improve treatment outcomes but also reduce side effects compared to traditional chemotherapy. By pairing acalabrutinib with bendamustine, rituximab (BR), and venetoclax (VR), researchers hope to tackle both treatment-naive and relapse refractory patients more effectively than current options.

What evidence suggests that this trial's treatments could be effective for Mantle Cell Lymphoma?

In this trial, one treatment arm combines the drugs acalabrutinib, bendamustine, and rituximab for treating mantle cell lymphoma. Research has shown that this combination can reduce the risk of disease progression or death by 27% in previously untreated patients. The FDA has approved this combination for mantle cell lymphoma, underscoring its effectiveness.

Another treatment arm uses acalabrutinib with venetoclax and rituximab. Early results are promising, with all study participants showing some positive response to the treatment. Both combinations offer hopeful options for those dealing with mantle cell lymphoma. ^{1 3 4 5 6}

Who Is on the Research Team?

Acerta Clinical Trials

Principal Investigator

1-888-292-9613; [e-mail]

Are You a Good Fit for This Trial?

This trial is for adults diagnosed with Mantle Cell Lymphoma (MCL) who have not been treated before. Participants must be in relatively good health, with an ECOG performance status of ≤ 2, and agree to use effective contraception. Pregnant or breastfeeding individuals, those with significant heart disease or gastrointestinal issues that affect drug absorption, or active infections are excluded.

Inclusion Criteria

I have mantle cell lymphoma and haven't received any treatment yet.

I can take care of myself but might not be able to do heavy physical work.

I agree to use effective birth control during and after the study for the required time.

Exclusion Criteria

I do not have any major issues with my stomach or intestines that affect how I absorb food or medicine.

I do not have an ongoing infection that is not improving with treatment.

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 in combination with bendamustine and rituximab or venetoclax and rituximab

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Acalabrutinib
• Bendamustine
• Rituximab
• Venetoclax

Trial Overview The study is testing Acalabrutinib combined with either Bendamustine and Rituximab (BR) or Venetoclax and Rituximab (VR). It's a Phase 1b trial where all participants receive the experimental treatment combinations to determine safety and dosage levels.

How Is the Trial Designed?

Group I: Part 2: Acalabrutinib+VR in TN patients Experimental Treatment 1 Intervention

Part 2: Acalabrutinib in combination with venetoclax and rituximab (VR) in treatment naive patients

Group II: Part 1: Acalabrutinib+BR in TN patients Experimental Treatment 1 Intervention

Part 1: Acalabrutinib in combination with drugs bendamustine and rituximab (BR) in treatment naive patients

Group III: Part 1: Acalabrutinib+BR in RR patients Experimental Treatment 1 Intervention

Part 1: Acalabrutinib in combination with bendamustine and rituximab (BR) in relapse refractory patients

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

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]

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]

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]

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, a selective BTK inhibitor, is effective for treating mantle cell lymphoma (MCL) in patients who have already undergone at least one therapy, with serious side effects being rare.

While common side effects like headaches are generally mild and resolve quickly, patients should be cautious about drug interactions and consult their physician before taking additional medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of acalabrutinib in patients with mantle cell lymphoma. Awan, FT., Jurczak, W.[2021]

Citations

1. 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 ...

2. 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 ...

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. 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) ...

5. 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 ...

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

Safety and efficacy of acalabrutinib plus bendamustine and ... After a median follow-up of 20.4 months, median PFS was 28.6 months and OS was not reached in the R/R cohort. Results indicate that ABR was safe ...