Acalabrutinib + Combination Therapy for B-Cell Lymphoma

Not currently recruiting at 41 trial locations

Overseen By Acerta Call center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Acerta Pharma BV

Disqualifiers: Cardiovascular disease, Malabsorption, Pregnancy, 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: Varies by regimen

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach for treating certain types of B-cell lymphoma, specifically follicular lymphoma (FL) and marginal zone lymphoma (MZL). Researchers aim to assess the safety and effectiveness of acalabrutinib, a targeted therapy, when used alone or with other drugs like rituximab and lenalidomide. The trial consists of different parts to test various combinations of these treatments. Individuals who have experienced a relapse or resistance to at least one prior therapy for FL or MZL might be suitable candidates for this study. As a Phase 1 and Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in lymphoma 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?

Research has shown that acalabrutinib, whether used alone or with other medications, is generally well-tolerated. Studies found acalabrutinib to be safer than similar treatments like ibrutinib. For patients with relapsed or hard-to-treat follicular lymphoma, about 20% experienced side effects, but these were usually manageable.

When combined with rituximab and lenalidomide, known as aR2, safety studies showed promising results. In one study, 92% of patients had a complete response, meaning no signs of cancer were found after treatment, indicating both safety and effectiveness.

Overall, while side effects can occur, the treatment has demonstrated a good safety profile in various studies. Always discuss potential risks and benefits with a healthcare professional before deciding to join a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about acalabrutinib combined with rituximab for treating B-cell lymphoma because it offers a unique approach compared to standard therapies like chemotherapy or rituximab alone. Acalabrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor, which means it targets specific enzymes involved in the growth of cancer cells, potentially leading to more precise and effective treatment. Unlike traditional chemotherapy, which can affect healthy cells, acalabrutinib specifically targets cancerous B-cells, potentially resulting in fewer side effects. Additionally, the combination with rituximab, a monoclonal antibody that targets the CD20 protein on B-cells, may enhance the overall effectiveness of the treatment, offering hope for better outcomes in patients with relapsed or refractory lymphoma.

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

Research shows that acalabrutinib, a type of medication, may help treat certain lymphomas. In this trial, participants may receive different combinations of treatments. Some will receive acalabrutinib with rituximab, which earlier studies have shown to be well-tolerated and effective in treating follicular lymphoma. Another study found this combination effective for both newly diagnosed and previously treated follicular lymphoma. Other participants will receive acalabrutinib with lenalidomide and rituximab, which has proven effective and safe for patients with untreated follicular lymphoma. This combination has also worked well and been safe for aggressive B-cell non-Hodgkin lymphoma that has returned or is hard to treat. These findings suggest that these treatment approaches could help manage these difficult types of lymphoma. ^{1 5 6 7 8}

Who Is on the Research Team?

Acerta Call center

Principal Investigator

Acerta Pharma, LLC

Are You a Good Fit for This Trial?

Adults over 18 with certain types of B-cell Non-Hodgkin Lymphoma that have relapsed or didn't respond to previous treatments. Participants must not be pregnant, should agree to use contraception if they can have children, and cannot have serious heart issues or gastrointestinal conditions that could affect the study.

Inclusion Criteria

Agreement to use contraception during the study and for 30 days after the last dose of study drugs if sexually active and able to bear or beget children

I have splenic marginal zone lymphoma with an additional measurable lesion.

I have Follicular Lymphoma that needs treatment and has either come back or didn't respond to previous treatments.

Exclusion Criteria

I do not have significant issues with my digestive system.

I do not have a severe illness that could risk my safety in the study.

Breastfeeding or pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive acalabrutinib alone or in combination with rituximab and lenalidomide for relapsed, refractory B-cell Non-Hodgkin Lymphoma

Varies by regimen

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Acalabrutinib
• Lenalidomide
• Rituximab

Trial Overview The trial is testing Acalabrutinib alone or combined with Rituximab for relapsed/refractory Follicular Lymphoma (FL), and its combination with Rituximab and Lenalidomide for the same condition. It aims to assess safety and effectiveness, including overall response rate in Marginal Zone Lymphoma (MZL).

How Is the Trial Designed?

Group I: Part 3: acalabrutinib Regimen 1 Experimental Treatment 3 Interventions

acalabrutinib Regimen + lenalidomide + rituximab for relapsed, refractory Follicular Lymphoma subjects

Group II: Part 2: acalabrutinib Regimen 2 Experimental Treatment 2 Interventions

acalabrutinib Regimen 2 + rituximab for relapsed, refractory Marginal Zone Lymphoma subjects

Group III: Part 2: acalabrutinib Regimen 1 Experimental Treatment 1 Intervention

acalabrutinib Regimen 1 for relapsed, refractory Marginal Zone Lymphoma subjects

Group IV: Part 1: acalabrutinib Regimen 2 Experimental Treatment 2 Interventions

acalabrutinib Regimen 2 + rituximab for relapsed, refractory, or treatment naive Follicular Lymphoma subjects

Group V: Part 1: acalabrutinib Regimen 1 Experimental Treatment 1 Intervention

acalabrutinib Regimen 1 for relapsed, refractory Follicular Lymphoma subjects

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

Rituximab plus bendamustine (R-B) is less toxic and achieves similar complete remission rates compared to R-CHOP in patients with follicular lymphoma grade 3A, with 97% vs. 96% complete remissions respectively.

Patients treated with R-B experienced significantly lower relapse rates (16% vs. 41%) and longer progression-free survival (15 years vs. 11.7 years) compared to those treated with R-CHOP, making R-B a more effective first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine plus Rituximab Versus R-CHOP as First-Line Treatment for Patients with Follicular Lymphoma Grade 3A: Evidence from a Multicenter, Retrospective Study. Mondello, P., Steiner, N., Willenbacher, W., et al.[2019]

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 study of 34 patients with relapsed/refractory chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL), maintenance therapy with lenalidomide after bendamustine and rituximab (BR) did not significantly improve progression-free survival (PFS), which was 18.3 months compared to 15.2 months without maintenance.

The study highlighted challenges with lenalidomide maintenance due to hematological and infectious toxicities, as only 6 out of 19 patients completed the intended 12 cycles, suggesting that lenalidomide may be more effective in earlier treatment settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine + rituximab chemoimmunotherapy and maintenance lenalidomide in relapsed, refractory chronic lymphocytic leukaemia and small lymphocytic lymphoma: A Wisconsin Oncology Network Study. Chang, JE., Havighurst, T., Kim, K., et al.[2018]

The combination of bendamustine and rituximab showed promising therapeutic efficacy in treating lymphoproliferative diseases, achieving an overall response rate of 65% in chronic lymphocytic leukemia (CLL) and 96% in indolent lymphoma among 71 patients studied.

However, the treatment was associated with significant hematotoxicity, with severe neutropenia and thrombocytopenia occurring in 33% and 18% of patients, respectively, and a notable risk of severe infections in aggressive lymphoma and CLL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Routine use of bendamustine and rituximab combination therapy in consecutive patients with lymphoproliferative diseases: a survey from Tyrolean hospitals. Waldthaler, C., Stauder, R., Schnallinger, 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]

In a study involving four patients with primary refractory or early relapsed T cell rich B cell lymphomas (TCRBCL), the combination of rituximab with chemotherapy (vinorelbine and gemcitabine) resulted in three complete responses and one partial response, demonstrating significant efficacy.

The treatment was well-tolerated, with no significant adverse effects reported, suggesting that rituximab combined with chemotherapy could be a promising option for treating TCRBCL and warrants further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in combination with vinorelbine/gemcitabine chemotherapy in patients with primary refractory or early relapsed T cell rich B cell lymphoma. A pilot study. Xiros, N., Economopoulos, T., Valsami, S., et al.[2022]

Rituximab, an anti-CD20 monoclonal antibody, significantly improves tumor remission and patient survival when used in combination with chemotherapy for patients with B-cell non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), based on phase III trials.

The drug is generally well tolerated and has been shown to prolong remission when used as maintenance therapy, making it a valuable treatment option included in current guidelines for advanced-stage B-cell NHL and CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on rituximab in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Cvetković, RS., Perry, CM.[2018]

Acalabrutinib, a Bruton tyrosine kinase inhibitor, showed a 53% overall response rate in patients with relapsed/refractory marginal zone lymphoma, indicating its efficacy in this patient population.

The treatment was generally well tolerated, with a median progression-free survival of 27.4 months and a low incidence of severe adverse events, suggesting improved safety compared to other treatments like ibrutinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2, multicentre, open-label trial (ACE-LY-003) of acalabrutinib in patients with relapsed or refractory marginal zone lymphoma. Strati, P., Coleman, M., Champion, R., et al.[2022]

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]

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]

Acalabrutinib, a selective BTK inhibitor, has shown improved progression-free survival in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) compared to standard treatments, indicating its efficacy as a treatment option.

The safety profile of acalabrutinib is favorable, with most side effects being mild (grade 1/2), such as headache and diarrhea, and a low rate of treatment discontinuation due to adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib: A Selective Bruton Tyrosine Kinase Inhibitor for the Treatment of B-Cell Malignancies. Abbas, HA., Wierda, WG.[2023]

Citations

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A phase 2, multicentre, open‐label trial (ACE‐LY‐003) of ... Acalabrutinib, a Bruton tyrosine kinase inhibitor, demonstrated greater selectivity and improved safety versus ibrutinib in a head‐to‐head trial in relapsed/ ...

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CALQUENCE® (acalabrutinib) plus chemoimmunotherapy ... Results showed the CALQUENCE combination regimen reduced the risk of disease progression or death by 27% compared to standard-of-care chemoimmunotherapy.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124105708

Real-World Effectiveness and Safety Outcomes of ... This RW study demonstrated that, among pts with MCL who received acala in the R/R setting, effectiveness was similar to a recently presented RW evidence study ...

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Frontline acalabrutinib, lenalidomide and rituximab for ... This phase II trial aims to determine the efficacy and safety of frontline acalabrutinib, lenalidomide and rituximab for patients with ...

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Calquence plus chemoimmunotherapy reduced the risk of ... Results showed the Calquence combination regimen reduced the risk of disease progression or death by 27% compared to standard-of-care chemoimmunotherapy.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10850340/

Advances in the treatment of relapsed/refractory marginal ... Marginal zone lymphoma (MZL) is the second most common subtype of inert B-cell non-Hodgkin's lymphoma, accounting for 5–15% of non-Hodgkin's lymphoma cases.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11637741/

Acalabrutinib alone or in combination with rituximab for ... In this open‐label, parallel‐group study, patients with relapsed/refractory (R/R) follicular lymphoma (FL) were randomised to either acalabrutinib monotherapy ...

8. vjhemonc.com vjhemonc.com/video/xnjypdobkhs-the-safety-and-efficacy-of-acalabrutinib-for-the-treatment-of-rr-mzl/

EHA 2022 | The safety and efficacy of acalabrutinib for the ... Shares some insights into the safety and efficacy of acalabrutinib for the treatment of relapsed/refractory marginal zone lymphoma (R/R MZL).