Acalabrutinib + Chemotherapy for Non-Hodgkin's Lymphoma

Overseen By Mark J Roschewski, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: CNS lymphoma, Pregnancy, Active infections, others

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

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: 10

132 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding acalabrutinib, a type of targeted therapy, to the usual chemotherapy can improve outcomes for people with certain aggressive types of non-Hodgkin's lymphoma, such as diffuse large B-cell lymphoma. Researchers aim to increase the number of people cured through this approach. The trial seeks participants diagnosed with these types of B-cell lymphomas who have not yet begun treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take medications that are moderate or strong CYP3A inhibitors or inducers, as these could interfere with the study drug.

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

Research shows that acalabrutinib is usually well-tolerated by patients. In earlier studies with mantle cell lymphoma patients, acalabrutinib caused few severe side effects. Most side effects were mild to moderate, such as headaches, tiredness, and diarrhea. Serious side effects were less common, making the drug relatively safe.

Acalabrutinib has already received approval for use in some types of lymphoma, supporting its safety profile. However, its use with rituximab and chemotherapy remains under study. This combination aims to improve treatment outcomes in aggressive B-cell lymphomas, like diffuse large B-cell lymphoma.

The current trial phase shows that researchers are still gathering detailed safety information. Participants should discuss potential risks and benefits with their healthcare provider before joining. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of acalabrutinib with chemotherapy for treating Non-Hodgkin's Lymphoma because it introduces a novel mechanism of action. Unlike standard treatments that often focus on directly attacking cancer cells with chemotherapy alone, acalabrutinib specifically targets and inhibits Bruton's tyrosine kinase (BTK), a key enzyme that helps cancer cells survive and multiply. This targeted approach could potentially enhance the effectiveness of traditional chemotherapy regimens like CHOP and DA-EPOCH, especially for patients who initially respond well to acalabrutinib. By integrating acalabrutinib with established therapies, there is hope for better outcomes, particularly in reducing tumor size more efficiently.

What evidence suggests that this trial's treatments could be effective for aggressive B-cell lymphomas?

Research has shown that acalabrutinib, one of the treatments in this trial, can help fight certain types of lymphoma when combined with other treatments. Participants will receive acalabrutinib with either DA-EPOCH-R or R-CHOP, based on their tumor reduction response. Studies have found that combining acalabrutinib with other medicines reduced the risk of disease progression or death by 27% compared to standard treatments. This suggests it could improve outcomes for patients with aggressive B-cell lymphomas, such as diffuse large B-cell lymphoma. Early results from using acalabrutinib with rituximab and chemotherapy also indicate promise in enhancing treatment effectiveness. These findings suggest that adding acalabrutinib to standard treatment might improve cure rates for this challenging condition. ^{1 2 4 6 7}

Who Is on the Research Team?

Mark J Roschewski, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults aged 18+ with untreated aggressive B-cell lymphomas, specifically diffuse large B-cell lymphoma or high-grade B-cell lymphoma. Participants must have measurable disease, adequate organ and marrow function, and be willing to use effective contraception. Pregnant women, those with CNS involvement by the cancer or certain other health conditions are excluded.

Inclusion Criteria

Effects of acalabrutinib on the developing human fetus are unknown. For these reasons the following measures apply: Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrollment. Women of childbearing potential (WOCBP) who are sexually active must agree to highly-effective contraception prior to study entry, for the duration of study participation, and for at least 2 days after the last dose of acalabrutinib or 12 months after the last dose of combined chemotherapy, whichever is later. Male subjects must use highly effective contraception prior to study entry, for the duration of study participation, and for 12 months after the last dose of combined chemotherapy; there is no contraception timing requirement post-last dose of acalabrutinib alone if male subject does not initiate chemotherapy on study after the acalabrutinib window. Participants must not be planning to conceive or father children within the projected duration of the trial, starting with the pre-screening/screening visit through 2 days after the last dose of acalabrutinib or 12 months after the last dose of combined chemotherapy, whichever is later. Ability of patient to understand and the willingness to sign a written informed consent document. Any HIV status will be included in this study; status must be confirmed prior to enrollment.

I have an aggressive type of B-cell lymphoma and have not been treated for it.

I can provide a tumor sample for study, or I'm willing to have a biopsy if needed.

Exclusion Criteria

I do not have an active hepatitis B infection or a positive hepatitis B PCR test.

I do not have any other cancer requiring ongoing treatment.

My lymphoma has spread to my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Multiple visits for tests and biopsies

Initial Treatment

Participants receive acalabrutinib for 14 days to assess initial response

2 weeks

1 visit for drug administration and assessment

Chemoimmunotherapy

Participants receive R-CHOP or DA-EPOCH-R, with or without acalabrutinib, based on initial response

18 weeks

6 cycles of 21 days each

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 2 years, then every 6 months for 3 years, then yearly

What Are the Treatments Tested in This Trial?

Interventions

• Acalabrutinib
• CHOP
• DA-EPOCH
• Rituximab

Trial Overview The trial is testing if adding acalabrutinib (a pill) to standard chemotherapy regimens (DA-EPOCH-R or R-CHOP) along with rituximab improves cure rates in aggressive B-cell lymphomas like diffuse large B-cell lymphoma. The treatment includes up to six cycles of therapy lasting 21 days each.

How Is the Trial Designed?

Group I: 1 Experimental Treatment 4 Interventions

Acalabrutinib 100 mg orally twice a day for 14 days; Following window: patients with \> or = to 25% tumor reduction, treat with DA-EPOCH-R or R-CHOP + acalabrutinib 100mg orally twice a day for the first 10 days, for 6 cycles; whereas, patients with \<25% tumor reduction, treat with DA-EPOCH-R or R-CHOP alone for 6 cycles

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

The ACCEPT trial is investigating the safety and efficacy of adding acalabrutinib, a second-generation Btk inhibitor, to the standard R-CHOP regimen in patients with untreated Diffuse Large B-cell Lymphoma (DLBCL), with a focus on establishing the recommended dose and assessing overall response rates.

This open-label trial includes up to 39 participants and aims to provide preliminary evidence on the combination's effectiveness and safety, potentially paving the way for larger Phase II/III trials in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ACCEPT - combining acalabrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) for Diffuse Large B-cell Lymphoma (DLBCL): study protocol for a Phase Ib/II open-label non-randomised clinical trial. Davies, A., Barrans, S., Burton, C., et al.[2021]

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 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 demonstrated a high overall response rate of 97% in treatment-naive patients with chronic lymphocytic leukemia (CLL), with a median follow-up of 53 months, indicating its strong efficacy as a monotherapy.

The treatment was generally safe, with serious adverse events reported in 38% of patients, but only 6% discontinued due to adverse effects, suggesting that acalabrutinib can be a durable and manageable option for patients with CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib in treatment-naive chronic lymphocytic leukemia. Byrd, JC., Woyach, JA., Furman, RR., 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]

In a study of 29 patients with advanced diffuse histiocytic lymphoma, the CHOP-B chemotherapy regimen resulted in a higher complete response rate of 87% compared to 64% for the ACOMLA regimen, indicating better efficacy for CHOP-B.

Despite the higher response rate with CHOP-B, both treatments had significant toxicity, including nonfatal sepsis and drug-related deaths, highlighting the need for careful monitoring during chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized study comparing doxorubicin, cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (ACOMLA) with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-B) in the treatment of diffuse histiocytic lymphoma. Newcomer, LN., Cadman, EC., Nerenberg, MI., et al.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10772531/

Final results and overall survival data from a phase II study ... The patients with blastoid/pleomorphic morphology in this analysis of acalabrutinib achieved an ORR (80.8%) as high as that in the overall study population, ...

2. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2024/calquence-acalabrutinib-plus-chemoimmunotherapy-reduced-the-risk-of-disease-progression-or-death-by-27-percentage-vs-standard-of-care-in-patients-with-untreated-mantle-cell-lymphoma-in-echo-phase-iii-trial.html

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. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7744/528340/Real-World-Effectiveness-and-Safety-Outcomes-of

Real-World Effectiveness and Safety Outcomes of ... Results: Among 181 pts with MCL treated with acala, 127 were treated in the R/R setting (study cohort) (acala monotherapy: 94 pts; combination ...

4. astrazeneca.com astrazeneca.com/media-centre/press-releases/2024/calquence-combination-improved-pfs-in-1l-mcl.html

Calquence combination regimen demonstrated statistically ... Calquence combination regimen demonstrated statistically significant and clinically meaningful improvement in progression-free survival in 1st- ...

5. bioinvent.com bioinvent.com/en/press/bioinvent-announces-promising-initial-efficacy-data-triple-combination-arm-bi-1206-rituximab

BioInvent announces promising initial efficacy data from ... BioInvent announces promising initial efficacy data from triple combination arm of BI-1206, rituximab and Calquence for the treatment of non-Hodgkin's lymphoma.

6. 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% compared to ...

7. ema.europa.eu ema.europa.eu/en/documents/variation-report/calquence-h-c-005299-ii-0026-epar-assessment-report-extention-indication_en.pdf

Calquence - European Medicines Agency MCL is a rare subtype of B-cell non-Hodgkin lymphoma (NHL) that accounts for approximately 7% of ... Nevertheless, the safety data of ...