Acalabrutinib + Liso-Cel for B-Cell Lymphoma

Recruiting at 1 trial location

Overseen By Connor Johnson, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Patrick C. Johnson, MD

Must not be taking: CYP3A4 inhibitors, Proton pump inhibitors

Disqualifiers: HIV, Hepatitis B, Hepatitis C, 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: 5

Duration: up to 1 year

27 Participants Needed

Trial Summary

What is the purpose of this trial?

This research is being done to assess the effectiveness and safety of acalabrutinib combined with lisocabtagene maraleucel (liso-cel) for people with relapsed/refractory aggressive B-cell lymphoma. This research study involves the study drug acalabrutinib in combination with lisocabtagene maraleuce

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot take certain medications like strong CYP3A4 inhibitors/inducers or proton pump inhibitors. You may need to switch to alternatives like H2-receptor antagonists or antacids.

What data supports the effectiveness of the treatment Acalabrutinib + Liso-Cel for B-Cell Lymphoma?

Research shows that combining lisocabtagene maraleucel (liso-cel) with acalabrutinib improved the function of CAR T-cells, which are a type of immune cell modified to better fight cancer, and enhanced tumor clearance in mice. Additionally, acalabrutinib has been shown to significantly extend the time before disease progression in patients with chronic lymphocytic leukemia, suggesting its potential benefit in B-cell lymphoma when used in combination with other therapies. ^{1 2 3 4 5}

How is the treatment Acalabrutinib + Liso-Cel unique for B-Cell Lymphoma?

The combination of Acalabrutinib, a Bruton tyrosine kinase inhibitor, and Lisocabtagene Maraleucel, a CAR T-cell therapy, is unique because it enhances the effectiveness of CAR T-cells in targeting CD19 B-cell malignancies, potentially improving tumor clearance and patient survival compared to using these therapies individually. ^{1 2 3 5 6}

Research Team

Connor Johnson, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

Adults (≥18 years) with aggressive B-cell non-Hodgkin lymphoma that's come back or hasn't responded to treatment, including specific subtypes like DLBCL. Must have tried at least two prior therapies and be in good enough health for leukapheresis. Can't join if pregnant, breastfeeding, HIV positive, have active hepatitis B/C, uncontrolled infections or certain heart conditions.

Inclusion Criteria

Bilirubin <= 2 x ULN (or <= 3.0 mg/dL for specific conditions)

My kidneys are functioning well enough to clear waste.

My blood counts are normal and my lungs work well.

Exclusion Criteria

I need medication for stomach acid.

I have trouble swallowing pills or have a serious stomach or intestine condition.

I had a stem cell transplant from a donor within the last 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one infusion of liso-cel and acalabrutinib capsules twice daily for up to one year, as long as treatment is tolerated and disease does not worsen

up to 1 year

Regular clinical visits as tolerated

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Clinical visits up to 5 years

Long-term follow-up

Medical records are monitored for up to 15 years to assess long-term outcomes

up to 15 years

Treatment Details

Interventions

• Acalabrutinib
• Lisocabtagene Maraleucel
• Lymphodepleting chemotherapy

Trial Overview The trial is testing the combination of acalabrutinib (a cancer drug) with lisocabtagene maraleucel (liso-cel), a type of CAR T-cell therapy. It aims to see how safe and effective this combo is for those who've relapsed or haven’t responded well to previous treatments.

Participant Groups

Group I: ACALABRUTINIB and LISOCABTAGENE MARALEUCEL Experimental Treatment 3 Interventions

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits, as tolerated for one year * Liso-cel * Acalabrutinib

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?

Patrick C. Johnson, MD

Lead Sponsor

Trials

2

Recruited

130+

Jeremy Abramson, MD

Lead Sponsor

Trials

1

Recruited

30+

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 comparing two CAR T cell therapies for relapsed or refractory large B cell lymphoma, lisocabtagene maraleucel (liso-cel) showed similar efficacy to axicabtagene ciloleucel (axi-cel) in terms of overall and complete response rates, based on data from 256 patients for liso-cel and 101 patients for axi-cel.

Liso-cel demonstrated a significantly better safety profile, with much lower odds of experiencing severe cytokine release syndrome and neurological events compared to axi-cel, indicating it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-adjusted indirect treatment comparison of liso-cel versus axi-cel in relapsed or refractory large B cell lymphoma. Maloney, DG., Kuruvilla, J., Liu, FF., et al.[2021]

Acalabrutinib is an effective treatment option for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), but it can cause unique adverse events and toxicities that need careful management.

Nurses play a crucial role in improving patient outcomes by educating patients about potential side effects, monitoring for clinical symptoms, and ensuring adherence to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib: Nursing Considerations for Use in Patients With Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma. Nierman, P.[2022]

The study shows that combining CAR T-cell therapy (specifically lisocabtagene maraleucel) with ibrutinib or acalabrutinib enhances the effectiveness of the CAR T-cells in treating CD19 B-cell malignancies, as evidenced by improved tumor clearance and prolonged survival in tumor-bearing mice.

Ibrutinib, in particular, was found to induce beneficial gene expression changes in CAR T-cells, promoting a memory-like T-cell phenotype, which may contribute to more durable responses against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor Potency of an Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy, Lisocabtagene Maraleucel in Combination With Ibrutinib or Acalabrutinib. Qin, JS., Johnstone, TG., Baturevych, A., 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]

The STELLAR study is a prospective multicenter trial designed to evaluate the safety and efficacy of combining acalabrutinib, a BTK inhibitor, with standard CHOP-R chemoimmunotherapy in newly diagnosed Richter's syndrome (RS), aiming to improve progression-free survival (PFS) for patients with this aggressive form of lymphoma.

This trial not only assesses the effectiveness of the combination treatment but also explores the mutational landscape of RS and the potential for identifying biomarkers that could predict treatment response, addressing urgent clinical needs in a high-risk patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The STELLAR trial protocol: a prospective multicentre trial for Richter's syndrome consisting of a randomised trial investigation CHOP-R with or without acalabrutinib for newly diagnosed RS and a single-arm platform study for evaluation of novel agents in relapsed disease. Appleby, N., Eyre, TA., Cabes, M., et al.[2023]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Matching-adjusted indirect treatment comparison of liso-cel versus axi-cel in relapsed or refractory large B cell lymphoma. [2021]

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

Acalabrutinib: Nursing Considerations for Use in Patients With Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma. [2022]

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

Antitumor Potency of an Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy, Lisocabtagene Maraleucel in Combination With Ibrutinib or Acalabrutinib. [2022]

4. England pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

The STELLAR trial protocol: a prospective multicentre trial for Richter's syndrome consisting of a randomised trial investigation CHOP-R with or without acalabrutinib for newly diagnosed RS and a single-arm platform study for evaluation of novel agents in relapsed disease. [2023]

6. 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]