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 phase Ib/II trial studies the side effects and efficacy of maintenance acalabrutinib following cellular therapy in treating patients with large B-cell lymphoma at very high risk of the cancer coming back. Acalabrutinib is a small molecular inhibitor that may interfere with the ability of cancer cells to grow and spread.

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.

How does the drug acalabrutinib differ from other treatments for large B-cell lymphoma?

Acalabrutinib is a second-generation drug that specifically targets and inhibits Bruton tyrosine kinase (BTK), making it more selective and potent compared to older treatments like ibrutinib. This increased selectivity may lead to fewer side effects and better adherence to treatment. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Acalabrutinib for treating large B-cell lymphoma?

Acalabrutinib has been shown to be effective in treating chronic lymphocytic leukemia (CLL) by significantly extending the time patients live without their disease getting worse compared to standard treatments. It works by targeting a specific protein that helps cancer cells grow, and it has been approved for use in CLL, suggesting potential benefits for other similar types of blood cancers. ^{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

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

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

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]

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 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]

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 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]

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]

Citations

1. 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]

2. England 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. [2021]

3. England pubmed.ncbi.nlm.nih.gov

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

4. United States 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. [2021]

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

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

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

Preclinical Evaluation of the Novel BTK Inhibitor Acalabrutinib in Canine Models of B-Cell Non-Hodgkin Lymphoma. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. [2018]