Acalabrutinib Maintenance for Large B-cell Lymphoma

Recruiting at 2 trial locations

Overseen By Vlad Kustanovitch

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: Strong CYP3A inhibitors

Disqualifiers: Heart failure, GvHD, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Approximately 9-12 months

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests acalabrutinib, a medicine that may stop cancer cells from growing, as a maintenance treatment for large B-cell lymphoma. The goal is to determine if this treatment is safe and effective in preventing cancer recurrence after cellular therapy. Suitable candidates have large B-cell lymphoma and have undergone specific types of stem cell or CAR T-cell therapy, particularly if their cancer is at high risk of returning. Participants will receive the treatment for up to a year, provided their disease does not progress and they do not experience severe side effects. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this potentially groundbreaking therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use strong CYP3A inhibitors or inducers, and you must not be on long-term posaconazole or similar medications. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that acalabrutinib is likely to be safe for humans?

Research has shown that acalabrutinib is usually well-tolerated by patients. In studies involving individuals with relapsed or hard-to-treat large B-cell lymphoma, acalabrutinib caused fewer unwanted side effects compared to some older treatments.

Common side effects include headache, diarrhea, and tiredness, which most patients can manage. Serious side effects are less common but can include infections or low blood cell counts.

Overall, acalabrutinib has been used safely in other types of cancer, suggesting it might be safe for treating large B-cell lymphoma as well. However, since the trial remains in its early stages, researchers continue to gather data to confirm this. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for large B-cell lymphoma?

Acalabrutinib is unique because it targets Bruton's tyrosine kinase (BTK), a key player in the growth of cancer cells in large B-cell lymphoma. Unlike traditional chemotherapy, which can affect both healthy and cancerous cells, acalabrutinib offers a more targeted approach, potentially leading to fewer side effects. Researchers are excited because this precision might result in a more effective and tolerable treatment option, giving patients a better quality of life during therapy. Plus, its flexibility in dosing schedules allows for tailored treatment plans, which can be adjusted based on individual patient needs and responses.

What evidence suggests that acalabrutinib might be an effective treatment for large B-cell lymphoma?

Research has shown that acalabrutinib effectively treats various types of lymphoma, including mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL). Studies indicate that acalabrutinib reduces the risk of disease progression or death in lymphoma patients. It binds effectively to its target proteins, inhibiting cancer cell growth. In this trial, participants will receive acalabrutinib in different dosing schedules across various groups. Patients with aggressive lymphoma, including those with high-risk scores, have also benefited from this treatment. These findings suggest that acalabrutinib could effectively treat large B-cell lymphoma, particularly for those at high risk of recurrence. ^{1 3 4 6 7}

Who Is on the Research Team?

Caspian Oliai

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with large B-cell lymphoma who've had a positive response to CAR T-cell therapy or stem cell transplant. They must have good kidney function, not be pregnant, and agree to use contraception. Exclusions include heart problems, recent transfusions, active infections, certain drug treatments, and inability to swallow pills.

Inclusion Criteria

- Hemoglobin > 8 g/dL independent of transfusions

- Absolute neutrophil count (ANC) > 500/uL (microliters)

My PET-CT scan shows partial or complete response 1-3 months after CAR T-cell therapy.

Exclusion Criteria

I received a platelet transfusion in the last week.

My kidney function is severely reduced.

I have not received a live virus vaccine in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive acalabrutinib maintenance following cellular therapy, starting between days 28-104 and continuing until day 365

Approximately 9-12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Acalabrutinib

Trial Overview

The trial tests acalabrutinib as a maintenance treatment after cellular therapy in patients at high risk of relapse. Acalabrutinib is designed to block cancer growth by inhibiting specific proteins within the cancer cells.

How Is the Trial Designed?

Group I: Group III (acalabrutinib) Experimental Treatment 1 Intervention

Beginning anytime between days 28-104, patients receive acalabrutinib PO BID until day 365 in the absence of disease progression or unacceptable toxicity.

Group II: Group II (acalabrutinib) Experimental Treatment 1 Intervention

Beginning day 60, patients receive acalabrutinib PO QD and then PO BID from day 74 if there are no dose reductions until day 365 in the absence of disease progression or unacceptable toxicity.

Group III: Group I (acalabrutinib) Experimental Treatment 1 Intervention

Beginning day 90, patients receive acalabrutinib PO QD and then PO BID once no longer on prophylactic antifungal (CYP34A inhibitors) until day 365 in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

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, 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, a second-generation BTK inhibitor, has been shown to be more potent and selective than the first-in-class BTK inhibitor, ibrutinib, in treating B cell malignancies.

The review highlights the growing availability of targeted therapies for B cell cancers, emphasizing the potential of acalabrutinib based on preclinical and clinical data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. Wu, J., Zhang, M., Liu, D.[2018]

In a phase 3 study involving 535 patients with treatment-naive chronic lymphocytic leukaemia, acalabrutinib combined with obinutuzumab or as a monotherapy significantly improved progression-free survival compared to the standard treatment of obinutuzumab with chlorambucil, with median survival not reached for the acalabrutinib groups versus 22.6 months for the chlorambucil group.

The safety profile of acalabrutinib was favorable, with fewer infusion reactions and a lower incidence of grade 3 or higher adverse events compared to the obinutuzumab-chlorambucil group, indicating it is a viable chemotherapy-free treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Sharman, JP., Egyed, M., Jurczak, W., 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]

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]

In a phase III study involving 310 patients with relapsed/refractory chronic lymphocytic leukemia (CLL), acalabrutinib monotherapy significantly improved progression-free survival (PFS) compared to investigator's choice treatments, with a median PFS not reached for acalabrutinib versus 16.5 months for the comparator group.

Acalabrutinib demonstrated a favorable safety profile, with serious adverse events occurring in 29% of patients, compared to 56% for idelalisib plus rituximab and 26% for bendamustine plus rituximab, indicating it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. Ghia, P., Pluta, A., Wach, M., et al.[2021]

Acalabrutinib, a second-generation BTK inhibitor, was shown to effectively inhibit BTK activity and cell proliferation in canine lymphoma cells, indicating its potential efficacy in treating B-cell malignancies.

In a clinical trial with 20 dogs, acalabrutinib was generally well tolerated, with a 25% overall response rate and a median progression-free survival of 22.5 days, suggesting it is a safe treatment option for canine B-cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of the Novel BTK Inhibitor Acalabrutinib in Canine Models of B-Cell Non-Hodgkin Lymphoma. Harrington, BK., Gardner, HL., Izumi, R., et al.[2018]

Citations

1.

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 ...

2.

pmc.ncbi.nlm.nih.gov

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

Final results and overall survival data from a phase II study ...

Acalabrutinib also demonstrated efficacy in patients with blastoid/pleomorphic morphology, high-risk MIPI score, and Ki-67 index >30% and >50%, which are poor ...

3.

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.

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8485664/

Acalabrutinib for treatment of diffuse large B-cell lymphoma

Consistent with previous results in CLL and MCL, median steady-state BTK target occupancy was 97% to 99% throughout the dosing interval, and was >90% for all ...

5.

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- ...

6.

ashpublications.org

ashpublications.org/blood/article/144/Supplement%201/3111/533668/Updated-Response-and-Safety-for-Acalabrutinib-Plus

Updated Response and Safety for Acalabrutinib Plus RICE ...

Conclusions: RICE-A was feasible in transplant eligible patients receiving 2L therapy for DLBCL. The observed ORR 82% and CR 60% with a 1 yr.

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02112526

Acalabrutinib (ACP-196), a Btk Inhibitor, for Treatment of de ...

Safety Profile of Acalabrutinib in Subjects With Relapsed or Refractory ABC DLBCL. Safety assessments included SAEs TEAEs, including AEs leading to ...