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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of combining two treatments: acalabrutinib (a Bruton tyrosine kinase inhibitor) and lisocabtagene maraleucel (a CD19-directed chimeric antigen receptor T cell therapy) for individuals with aggressive B-cell lymphoma that has returned or not responded to previous treatments. B-cell lymphomas are cancers of the immune system, and the study aims to determine if these treatments can effectively combat the cancer together. The trial targets those who have already tried at least two treatments, including a CD20-targeted agent, and still have measurable disease. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that some safety information is available for acalabrutinib and lisocabtagene maraleucel (liso-cel) from earlier studies. Acalabrutinib is usually well-tolerated, with common side effects like headache and diarrhea, which are generally manageable. Liso-cel has demonstrated promising effectiveness but can cause more serious side effects, such as low blood cell counts and cytokine release syndrome (CRS), where the immune system becomes overly active.

In previous studies, liso-cel had a low rate of severe CRS and other serious side effects in patients who had already received many treatments. This suggests that while risks exist, they might be lower compared to other similar treatments. It's important to remember that this is still a trial, so safety monitoring continues. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment combination of Acalabrutinib and Lisocabtagene Maraleucel for B-cell lymphoma because it offers a novel approach compared to existing therapies. Acalabrutinib is a next-generation BTK inhibitor, which works by blocking a protein that helps cancer cells grow, while Lisocabtagene Maraleucel is a CAR T-cell therapy that reprograms the body’s own immune cells to attack cancer cells. This dual approach not only targets cancer cells more precisely but also leverages the body’s immune system for a potentially more powerful and sustained response. Unlike traditional chemotherapy or monoclonal antibodies, this combination could offer improved efficacy with potentially fewer side effects.

What evidence suggests that acalabrutinib combined with lisocabtagene maraleucel could be effective for B-cell lymphoma?

Research has shown that using acalabrutinib with lisocabtagene maraleucel (liso-cel) holds promise for treating aggressive B-cell lymphoma that has returned or resisted other treatments. Participants in this trial will receive this combination, which effectively targets cancer cells. The treatment is well-tolerated, as patients did not experience severe side effects. Liso-cel, a type of CAR T-cell therapy, uses specially modified immune cells to fight cancer and has shown positive results in similar conditions in past studies. Acalabrutinib helps stop cancer cell growth and has proven effective in other blood cancer trials. Together, these treatments offer hope for better outcomes in this challenging condition. ^{1 2 3 6 7}

Who Is on the Research Team?

Connor Johnson, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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

My kidneys are functioning well enough to clear waste.

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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]

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 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]

Citations

1. fda.gov fda.gov/media/179344/download

May 15, 2024 Clinical Review Memo - BREYANZI The benefit-risk assessment for lisocabtagene maraleucel (liso-cel) for the indicated population is based on the results of Study. 017001 MCL ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05583149

Acalabrutinib + Liso-Cel In R/R Aggressive B-Cell ... This research is being done to assess the effectiveness and safety of acalabrutinib combined with lisocabtagene maraleucel (liso-cel) for people with relapsed/ ...

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/hon.70093_140

PHASE 2 TRIAL OF LISOCABTAGENE MARALEUCEL ... Conclusion: Acalabrutinib plus liso-cel demonstrated encouraging efficacy outcomes and was well-tolerated. Future work will examine correlative ...

4. trialx.com trialx.com/clinical-trials/listings/288085/acalabrutinib-liso-cel-in-rr-aggressive-b-cell-lymphomas/?&geo_lat=42.4829&geo_lng=-71.1574&radius=10&place=Woburn&user_country=United%20States

Acalabrutinib + Liso-Cel In R/R Aggressive B-Cell ... This research is being done to assess the effectiveness and safety of acalabrutinib combined with lisocabtagene maraleucel (liso-cel) for people ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10981676/

Combination of acalabrutinib with lenalidomide and rituximab ... Combination of acalabrutinib with lenalidomide and rituximab in relapsed/refractory aggressive B-cell non-Hodgkin lymphoma: a single-arm phase II trial

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-00366

Acalabrutinib and Lisocabtagene Maraleucel for the ... This phase II trial tests how well acalabrutinib in combination with lisocabtagene maraleucel works in treating patients with aggressive B-cell lymphoma (a ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02214

Lisocabtagene Maraleucel in Relapsed/Refractory Mantle ... Liso-cel demonstrated high CR rate and deep, durable responses with low incidence of grade ≥3 CRS, NE, and infections in patients with heavily pretreated R/R ...