Acalabrutinib + BR/VR for Mantle Cell Lymphoma

Recruiting at 27 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

72 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Acalabrutinib for Mantle Cell Lymphoma?

Acalabrutinib has received accelerated approval from the FDA for treating mantle cell lymphoma based on a phase II study, and it is currently being evaluated in phase III trials. It is a selective Bruton tyrosine kinase inhibitor, which has shown efficacy in patients with relapsed or refractory mantle cell lymphoma. ^{1 2 3 4 5}

What makes the drug combination of Acalabrutinib, Bendamustine, Rituximab, and Venetoclax unique for treating Mantle Cell Lymphoma?

This drug combination is unique because it includes Acalabrutinib, a highly selective Bruton tyrosine kinase inhibitor, which has shown superior efficacy and a favorable safety profile in treating relapsed or refractory Mantle Cell Lymphoma compared to other targeted therapies. The combination with Bendamustine, Rituximab, and Venetoclax aims to enhance treatment effectiveness by targeting different pathways involved in the cancer's growth. ^{1 3 4 6 7}

What is the purpose of this trial?

A Phase 1b, Multicenter, Open-label Study of Acalabrutinib in Combination with Bendamustine and Rituximab (BR) or Venetoclax and Rituximab (VR) in Subjects with Mantle Cell Lymphoma

Research Team

Acerta Clinical Trials

Principal Investigator

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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, 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 (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]

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 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]

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]

References

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

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

2. 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]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Acalabrutinib: First Global Approval. [2018]

4. United States 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. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Use of acalabrutinib in patients with mantle cell lymphoma. [2021]

6. United States 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. [2022]

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

Combination of rituximab, bendamustine, and cytarabine for patients with mantle-cell non-Hodgkin lymphoma ineligible for intensive regimens or autologous transplantation. [2022]