Acalabrutinib + Combination Therapy for B-Cell Lymphoma

Recruiting at 40 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

113 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination Acalabrutinib, Lenalidomide, and Rituximab for B-Cell Lymphoma?

Rituximab, when used with chemotherapy, has shown significant effectiveness in treating various types of B-cell lymphomas, including non-Hodgkin lymphoma and chronic lymphocytic leukemia, by improving tumor remission and patient survival. This suggests that Rituximab, as part of a combination therapy, could be effective in treating B-cell lymphoma. ^{1 2 3 4 5}

Is Acalabrutinib safe for humans?

Acalabrutinib has been shown to have a generally acceptable safety profile in humans, with common side effects including headache, diarrhea, and infections. Some studies noted an increased risk of neutropenia (low white blood cell count) and leukopenia (reduced white blood cells), but overall, it was considered to have a favorable safety profile compared to other treatments. ^{6 7 8 9 10}

How is the drug Acalabrutinib unique for treating B-cell lymphoma?

Acalabrutinib is a highly selective Bruton tyrosine kinase inhibitor, which means it specifically targets a protein that helps cancer cells grow, making it potentially more effective and safer than other treatments. It has shown improved safety outcomes compared to similar drugs, with fewer off-target effects, and is used in combination with Rituximab to enhance its effectiveness in treating B-cell lymphoma. ^{6 7 8 9 11}

What is the purpose of this trial?

Part 1: To characterize the safety profile of acalabrutinib alone or in combination with rituximab in subjects with R/R FL. Part 2: To characterize the activity of acalabrutinib alone or in combination with rituximab in subjects with R/R MZL, as measured by ORR. Part 3: To characterize the safety of acalabrutinib in combination with rituximab and lenalidomide in subjects with R/R FL

Research Team

Acerta Call center

Principal Investigator

Acerta Pharma, LLC

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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 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 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]

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, 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]

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]

References

1. England 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. [2018]

2. England 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. [2022]

3. Austria pubmed.ncbi.nlm.nih.gov

Routine use of bendamustine and rituximab combination therapy in consecutive patients with lymphoproliferative diseases: a survey from Tyrolean hospitals. [2021]

4. England 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. [2019]

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

Spotlight on rituximab in non-Hodgkin lymphoma and chronic lymphocytic leukemia. [2018]

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

Acalabrutinib: Managing Adverse Events and Improving Adherence in Patients With Mantle Cell Lymphoma. [2022]

7. 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]

8. England pubmed.ncbi.nlm.nih.gov

EMA Review of Acalabrutinib for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia. [2021]

9. England 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. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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