50 Participants Needed

Acalabrutinib + CAR T-cell Therapy for B-Cell Lymphoma

AK
Overseen ByAjay K. Gopal
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

What is the purpose of this trial?

This phase I/II trial studies the safety of acalabrutinib and axicabtagene ciloleucel in treating patients with B-cell lymphoma. Acalabrutinib may stop the growth of tumor cells by blocking key pathways needed for cell growth. Immunotherapy with axicabtagene ciloleucel is engineered to target a specific surface antigen on lymphoma cells. Acalabrutinib may enhance the efficacy of axicabtagene ciloleucel in treating patients with B-cell lymphoma.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you cannot use strong CYP3A inhibitors or inducers within 7 days of starting the study drugs. If you are on a proton pump inhibitor, you may need to switch to a different type of medication.

What data supports the effectiveness of the treatment Acalabrutinib + CAR T-cell Therapy for B-Cell Lymphoma?

Axicabtagene ciloleucel, a component of the treatment, has shown high response rates and a manageable safety profile in patients with relapsed or refractory B-cell malignancies, including large B-cell lymphoma, and is approved by the FDA for such conditions. In a study, it achieved a 78% complete response rate as part of first-line therapy for high-risk large B-cell lymphoma.12345

What safety data exists for Acalabrutinib + CAR T-cell Therapy in humans?

Axicabtagene ciloleucel (Yescarta), a CAR T-cell therapy, has been studied for B-cell lymphoma and shows a manageable safety profile. Common side effects include cytokine release syndrome (a condition where the immune system is overly activated) and neurological events, but severe cases are less common. No treatment-related deaths were reported in the studies reviewed.13678

How is the treatment Acalabrutinib + CAR T-cell Therapy different for B-Cell Lymphoma?

This treatment combines Acalabrutinib, a drug that targets specific proteins in cancer cells, with Axicabtagene Ciloleucel, a CAR T-cell therapy that uses modified immune cells to attack cancer. This combination is unique because it targets the cancer in two different ways, potentially improving effectiveness for patients with relapsed or refractory B-cell lymphoma who have limited treatment options.125910

Research Team

AG

Ajay K. Gopal

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

Adults with B-cell lymphoma eligible for axi-cel per FDA, understanding and consenting to the study, ECOG status of 0-1, adequate organ function, no active infections or second cancers needing treatment. Excludes those intolerant to acalabrutinib, with brain metastases or cerebrospinal fluid malignant cells, on strong CYP3A inhibitors/inducers, refractory to BTK inhibition, low blood counts, pregnant/breastfeeding women.

Inclusion Criteria

I have been diagnosed with a specific type of large B-cell lymphoma.
My kidney function is good, with a creatinine clearance over 50 mL/min or serum creatinine <= 2.5.
I breathe well with minimal shortness of breath and my oxygen level is above 92% without assistance.
See 18 more

Exclusion Criteria

I do not have any serious infections that would make treatment risky.
I have not had major surgery in the last 7 days or have fully recovered from it.
I have or had cancer cells in my brain or spinal fluid.
See 18 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-3 weeks

Treatment

Participants receive acalabrutinib orally every 12 hours and axicabtagene ciloleucel intravenously after lymphodepleting chemotherapy

Up to 3 weeks for acalabrutinib prior to leukapheresis, followed by axicabtagene ciloleucel infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years
Every 3 months

Treatment Details

Interventions

  • Acalabrutinib
  • Axicabtagene Ciloleucel
Trial OverviewThe trial is testing the combination of acalabrutinib (a drug that blocks tumor growth pathways) and axicabtagene ciloleucel (a CAR T-cell therapy targeting lymphoma cells). It aims to see if acalabrutinib can boost the effectiveness of the immunotherapy in treating B-cell lymphoma.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (acalabrutinib, axicabtagene ciloleucel)Experimental Treatment2 Interventions
Beginning up to 3 weeks and at least 24 hours prior to leukapheresis, patients receive acalabrutinib PO every 12 hours. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also receive axicabtagene ciloleucel IV at 36-96 hours after completion of lymphodepleting chemotherapy.

Acalabrutinib is already approved in United States, European Union for the following indications:

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Approved in United States as Calquence for:
  • Mantle cell lymphoma
  • Chronic lymphocytic leukemia
  • Small lymphocytic lymphoma
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Approved in European Union as Calquence for:
  • Chronic lymphocytic leukemia
  • Small lymphocytic lymphoma
  • Mantle cell lymphoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials
1,858
Recruited
2,023,000+

AstraZeneca

Industry Sponsor

Trials
4,491
Recruited
290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from ร‰cole nationale vรฉtรฉrinaire 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 ร‰cole nationale vรฉtรฉrinaire 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

Axicabtagene ciloleucel (axi-cel) demonstrated impressive efficacy in treating relapsed/refractory large B-cell lymphoma, with overall and complete response rates of 83% and 58%, respectively, in the pivotal ZUMA-1 trial with a median follow-up of 27.1 months.
While axi-cel shows promise, it is associated with significant toxicities, including cytokine release syndrome (CRS) in 7% to 14% of patients and immune effector cell-associated neurotoxicity syndrome (ICANS) in 31% to 55%, highlighting the need for careful patient management and monitoring.
Axicabtagene Ciloleucel: Clinical Data for the Use of CAR T-cell Therapy in Relapsed and Refractory Large B-cell Lymphoma.Halford, Z., Anderson, MK., Bennett, LL.[2021]
Axicabtagene ciloleucel (axi-cel) is an effective CAR T-cell therapy targeting CD19, showing high response rates and a manageable safety profile in patients with relapsed or refractory B-cell malignancies, particularly after two or more lines of prior treatment.
Axi-cel is FDA-approved for adult patients with specific types of B-cell lymphomas, including diffuse large B-cell lymphoma, and is currently being studied for its efficacy in other B-cell malignancies in ongoing clinical trials.
Axicabtagene ciloleucel for the treatment of relapsed/refractory B-cell non-Hodgkin's lymphomas.Sharma, P., King, GT., Shinde, SS., et al.[2018]
In the ZUMA-12 study involving 40 patients with high-risk large B-cell lymphoma, axicabtagene ciloleucel (axi-cel) demonstrated a high complete response rate of 78% and an overall response rate of 89%, indicating its effectiveness as a first-line treatment.
The safety profile of axi-cel was manageable, with only 8% of patients experiencing severe cytokine release syndrome and 23% experiencing neurological events, and no treatment-related deaths were reported.
Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial.Neelapu, SS., Dickinson, M., Munoz, J., et al.[2023]

References

Axicabtagene Ciloleucel: Clinical Data for the Use of CAR T-cell Therapy in Relapsed and Refractory Large B-cell Lymphoma. [2021]
Axicabtagene ciloleucel for the treatment of relapsed/refractory B-cell non-Hodgkin's lymphomas. [2018]
Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial. [2023]
Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. [2023]
Axicabtagene Ciloleucel in Combination with the 4-1BB Agonist Utomilumab in Patients with Relapsed/Refractory Large B-Cell Lymphoma: Phase 1 Results from ZUMA-11. [2023]
New Second-Line Treatment for B-Cell Lymphoma. [2022]
Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity. [2022]
EMA Review of Axicabtagene Ciloleucel (Yescarta) for the Treatment of Diffuse Large B-Cell Lymphoma. [2022]
Use of Chimeric Antigen Receptor T Cell Therapy in Clinical Practice for Relapsed/Refractory Aggressive B Cell Non-Hodgkin Lymphoma: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy. [2020]
CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products. [2020]