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.
What safety data is available for Acalabrutinib + CAR T-cell Therapy in B-Cell Lymphoma?The safety data for axicabtagene ciloleucel (axi-cel), a CAR T-cell therapy used in B-cell lymphoma, indicates that it has a manageable safety profile. In the ZUMA-12 trial, grade ≥3 cytokine release syndrome (CRS) and neurologic events occurred in 8% and 23% of patients, respectively, with no treatment-related grade 5 events. Common adverse events include cytokine release syndrome, neurological events, infections, pyrexia, diarrhea, nausea, hypotension, and fatigue. The therapy has been approved for use in relapsed/refractory large B-cell lymphoma and has shown consistent safety outcomes in both clinical trial and non-trial settings. However, specific safety data for the combination of Acalabrutinib with CAR T-cell therapy is not detailed in the provided research.56789
What data supports the idea that Acalabrutinib + CAR T-cell Therapy for B-Cell Lymphoma is an effective treatment?The available research shows that axicabtagene ciloleucel, a part of the CAR T-cell therapy, is effective for treating B-cell lymphoma. In the ZUMA-12 trial, 78% of patients had a complete response, meaning their cancer was no longer detectable, and 89% had an overall positive response. This suggests that the treatment is highly effective, especially for high-risk cases. Additionally, the treatment has a manageable safety profile, with serious side effects occurring in a small percentage of patients. Compared to standard treatments, which often have poor outcomes, this therapy offers a promising alternative.127810
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you must stop all current medications. However, you cannot use strong CYP3A inhibitors or inducers within 7 days of starting the study drugs. If you're on a proton pump inhibitor, you must switch to an H2-receptor antagonist or antacid. Consult with your doctor for specific guidance.
Is the treatment Acalabrutinib, Axicabtagene Ciloleucel a promising treatment for B-cell lymphoma?Yes, Axicabtagene Ciloleucel is a promising treatment for B-cell lymphoma. It is a type of CAR T-cell therapy that has shown high response rates in patients with difficult-to-treat B-cell lymphomas. It is approved by health authorities in several countries and has transformed the treatment landscape for these cancers.234710
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.
I meet the FDA requirements for axi-cel treatment.
I am HIV positive and do not have any uncontrolled infections.
My heart pumps well and I don't have fluid around it.
I can understand and sign the consent form.
I am 18 years old or older.
I am fully active or can carry out light work.
I am HIV positive without any current severe infections needing antibiotics.
I am HIV positive with a hemoglobin level above 8.0 g/dl.
Exclusion Criteria
I do not have active hepatitis B as confirmed by negative tests.
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.
I cannot swallow pills or have a condition affecting my stomach or intestines that impacts how I absorb medication.
I have a history of seizures, stroke, memory disorders, or autoimmune diseases affecting my brain.
I do not have active bleeding or a history of bleeding disorders like hemophilia.
My condition did not improve with BTK inhibitor treatment.
I haven't taken strong CYP3A drugs in the last week and don't need them now.
I have uncontrolled AIHA or ITP.
Treatment Details
The 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.
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:
🇺🇸 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
Find a clinic near you
Research locations nearbySelect from list below to view details:
Fred Hutch/University of Washington Cancer ConsortiumSeattle, WA
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Who is running the clinical trial?
University of WashingtonLead Sponsor
AstraZenecaIndustry Sponsor
References
Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. [2023]In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy.
Axicabtagene ciloleucel for the treatment of relapsed/refractory B-cell non-Hodgkin's lymphomas. [2018]B-cell non-Hodgkin's lymphomas are the most common hematological malignancies, which despite improvements in chemo-immunotherapy, carry a uniformly poor prognosis in the relapsed/refractory setting. CD19 is an antigen expressed on the surface of most malignancies arising from the B cells, and adoptive transfer of anti-CD19 chimeric antigen receptor (CAR)-expressing T cells has been shown to be effective in treating these B-cell malignancies. Axicabtagene ciloleucel (axi-cel, KTE-C19) is an autologous anti-CD19 CAR T-cell therapy which has shown high overall response rates and a manageable safety profile in patients with relapsed or refractory B-cell malignancies who lack effective and curative treatment options. Axi-cel is currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma and DLBCL arising from follicular lymphoma, and is also being evaluated in other B-cell malignancies in ongoing clinical trials. In this review we will discuss the mechanism of action of axi-cel, clinical trials leading to its FDA approval, ongoing clinical trials and its potential adverse effects, and will speculate on the future directions of axi-cel and CAR T-cell therapy in general.
CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products. [2020]Adoptive cellular immunotherapy with chimeric antigen receptor (CAR) T cell has changed the treatment landscape of B-cell non-Hodgkin's lymphoma (NHL), especially for aggressive B-cell lymphomas. Single-center and multicenter clinical trials with anti-CD19 CAR T-cell therapy have shown great activity and long-term remissions in poor-risk diffuse large B-cell lymphoma (DLBCL) when no other effective treatment options are available. Two CAR T-cell products [axicabtagene ciloleucel (axi-cel) and tisagenlecleucel] have obtained US Food and Drug Administration approval for the treatment of refractory DLBCL after two lines of therapy. A third product, liso-cel, is currently being evaluated in clinical trials and preliminary results appear very promising. CAR T-cell-related toxicity with cytokine-release syndrome and neurotoxicity remain important potential complications of this therapy. Here, we review the s biology, structure, clinical trial results and toxicity of two commercially approved CAR T-cell products and others currently being studied in multicenter clinical trials in B-cell NHLs.
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]Axicabtagene ciloleucel (YESCARTA; Kite Pharma, a Gilead Company, Los Angeles CA) and tisagenlecleucel (KYMRIAH; Novartis Pharmaceuticals Corp., Basel, Switzerland) are two CD19-directed chimeric antigen receptor (CAR) T cell products currently approved by the US Food and Drug Administration; the European Medicines Agency; Health Canada; Ministry of Health, Labor and Welfare (Japan); and Therapeutic Goods Administration (Australia) for treatment of specific subtypes of relapsed/refractory aggressive B cell non-Hodgkin lymphoma (NHL). Although this approval has been transformative in the use of cellular immunotherapy in lymphoma, there are concerns regarding appropriate use of this novel therapy and of short- and long-term toxicities. To address these issues, representatives of the American Society of Transplantation and Cellular Therapy convened to recognize and address key issues surrounding the clinical application of CD19 CAR T cell therapy in B cell lymphomas, in collaboration with worldwide experts. The aim of this article is to provide consensus opinion from experts in the fields of hematopoietic cell transplantation, cellular immunotherapy, and lymphoma regarding key clinical questions pertinent to the use of CD19 CAR T cell products for the treatment of NHL. As the clinical practice using CAR T cells grows worldwide, we anticipate that this guidance will be relevant for hematology/oncology physicians who care for patients with lymphomas.
EMA Review of Axicabtagene Ciloleucel (Yescarta) for the Treatment of Diffuse Large B-Cell Lymphoma. [2022]On June 28, 2018, the Committee for Advanced Therapies and the Committee for Medicinal Products for Human Use adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Yescarta for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma, after two or more lines of systemic therapy. Yescarta, which was designated as an orphan medicinal product and included in the European Medicines Agency's Priority Medicines scheme, was granted an accelerated review timetable. The active substance of Yescarta is axicabtagene ciloleucel, an engineered autologous T-cell immunotherapy product whereby a patient's own T cells are harvested and genetically modified ex vivo by retroviral transduction using a retroviral vector to express a chimeric antigen receptor (CAR) comprising an anti-CD19 single chain variable fragment linked to CD28 costimulatory domain and CD3-zeta signaling domain. The transduced anti-CD19 CAR T cells are expanded ex vivo and infused back into the patient, where they can recognize and eliminate CD19-expressing cells. The benefits of Yescarta as studied in ZUMA-1 phase II (NCT02348216) were an overall response rate per central review of 66% (95% confidence interval, 56%-75%) at a median follow-up of 15.1 months in the intention to treat population and a complete response rate of 47% with a significant duration. The most common adverse events were cytokine release syndrome, neurological adverse events, infections, pyrexia, diarrhea, nausea, hypotension, and fatigue. IMPLICATIONS FOR PRACTICE: Yescarta (axicabtagene ciloleucel) was the first chimeric antigen receptor T-cell therapy to be submitted for evaluation to the European Medicines Agency and admitted into the "priority medicine" scheme; it was granted accelerated assessment on the basis of anticipated clinical benefit in relapsed/refractory diffuse large B-cell lymphoma, a condition of unmet medical need. Indeed, Yescarta showed an overall response rate of 66% and a complete response rate of 47% with a significant duration and a manageable toxicity that compared very favorably with historical controls. Here the analysis of benefits and risks is presented, and specific challenges with this important novel product are highlighted, providing further insights and reflections for future medical research.
Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity. [2022]Axicabtagene ciloleucel (axi-cel) was approved by the Food and Drug Administration for relapsed aggressive B-cell non-Hodgkin lymphoma in part on the basis of durable remission rates of approximately 40% in a clinical trial population. Whether this efficacy, and the rates of toxicity, would be consistent in a postcommercial setting, with relaxed eligibility criteria and bridging therapy, is unknown. This study describes the efficacy and safety correlates and outcomes in this setting.
Axicabtagene Ciloleucel: Clinical Data for the Use of CAR T-cell Therapy in Relapsed and Refractory Large B-cell Lymphoma. [2021]To evaluate the literature for axicabtagene ciloleucel (axi-cel), a first-in-class chimeric antigen receptor (CAR) T-cell therapy, in the treatment of relapsed/refractory (r/r) large B-cell lymphoma (LBCL).
Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial. [2023]High-risk large B-cell lymphoma (LBCL) has poor outcomes with standard first-line chemoimmunotherapy. In the phase 2, multicenter, single-arm ZUMA-12 study (ClinicalTrials.gov NCT03761056) we evaluated axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, as part of first-line treatment in 40 patients with high-risk LBCL. This trial has completed accrual. The primary outcome was complete response rate (CRR). Secondary outcomes were objective response rate (ORR), duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), overall survival (OS), assessment of safety, central nervous system (CNS) relapse and blood levels of CAR T cells and cytokines. The primary endpoint in efficacy-evaluable patients (n = 37) was met, with 78% CRR (95% confidence interval (CI), 62-90) and 89% ORR (95% CI, 75-97). As of 17 May 2021 (median follow-up, 15.9 months), 73% of patients remained in objective response; median DOR, EFS and PFS were not reached. Grade ≥3 cytokine release syndrome (CRS) and neurologic events occurred in three patients (8%) and nine patients (23%), respectively. There were no treatment-related grade 5 events. Robust CAR T-cell expansion occurred in all patients with a median time to peak of 8 days. We conclude that axi-cel is highly effective as part of first-line therapy for high-risk LBCL, with a manageable safety profile.
New Second-Line Treatment for B-Cell Lymphoma. [2022]Axicabtagene ciloleucel (Yescarta) has been approved for use as a second-line drug in patients with large B-cell lymphoma who are resistant to, or who relapse within 12 months of, first-line chemoimmunotherapy.Confirming the patient's identity and matching it to the drug are critical as this is an autologous infusion. Nurses should premedicate patients to minimize the risk of hypersensitivity reactions.
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]Chimeric antigen receptor (CAR) T-cell therapies have shown clinical benefit for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL), yet approximately 60% of patients do not respond or eventually relapse. We investigated the safety and feasibility of the CD19-directed CAR T-cell therapy axicabtagene ciloleucel (axi-cel) in combination with the 4-1BB agonist antibody utomilumab as an approach to improve efficacy of CAR T-cell therapy.