Single-arm, open-label, multicenter, phase II trial aiming to include approximately 45 patients over 24 months. Patients will receive axicabtagene ciloleucel infusion and will be followed up to 5 years. The total duration of the study is therefore of 7 years.
Axicabtagene Ciloleucel , an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, demonstrated a high rate of durable responses with a manageable safety profile, in patients with relapsed or refractory large B-cell lymphoma (LBCL) after two or more previous therapies. Recently, axicabtagene ciloleucel as demonstrated superior efficacy compared to standard of care (SOC) in 2nd line LBCL patients considered eligible for autologous stem-cell transplantation (ASCT) with primary refractory disease or early relapse (ZUMA-7). In this study, after a median follow-up of 24.9 months, the median event-free survival was 8.3 months in the axicabtagene ciloleucel group and 2.0 months in the standard-care group, and the 24-month event-free survival was 41% and 16%, respectively (hazard ratio, \[HR\] for event or death, 0.40; 95% confidence interval, 0.31 to 0.51; p\<0.001). Some response occurred in 83% of the patients in the axicabtagene ciloleucel group and in 50% of those in the SOC group (with a complete response \[CR\] in 65% and 32% of the patients, respectively). These data led to the approval of axicabtagene ciloleucel by the American and European regulatory agencies, for patients with LBCL refractory to first-line or relapsing within the first year after completion of induction immunochemotherapy. More recently, the open-label phase 2 ALYCANTE trial assessed the safety and efficacy of axicabtagene ciloleucel as second-line therapy in patients with primary refractory or early relapsed aggressive B-cell lymphoma who were not deemed candidates for ASCT. Treatment with axicabtagene ciloleucel resulted in high response rates (best overall response 92.5%, best CR = 80.0%) and durable remissions (median PFS, 11 months, median overall survival \[OS\], not reached), with an acceptable safety profile in this population of patients considered unfit for ASCT. The above-mentioned trials included only patients who were primary refractory or had relapsed within a year of completing first-line treatment. However, no data are available on the efficacy of axicabtagene ciloleucel in second line for patients relapsing more than one year after completion of induction. Although it is generally assumed that the outcome of these patients is better than that of patients showing early failure, still the outcome is not optimal at all, with at least half of the patients dying from the lymphoma in the next months. The current proposal is aimed at studying a possible role of axicabtagene ciloleucel in this subset of cases.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
45
Treatment consists of a single dose for infusion containing a dispersion for infusion of CAR-positive viable T cells in one infusion bag. The target dose is 2 × 106 CAR-positive viable T cells per kg of body weight (within a range of 1 × 106 - 2 × 106 cells/kg), with a maximum of 2 × 108 CAR-positive viable T cells for patients 100 kg and above.
Complejo Hospitalario Universitario A Coruña
A Coruña, A Coruña, Spain
RECRUITINGHospital Universitario Son Espases
Response month 3
The Complete Metabolic Response, defined as negative findings on a PET/CT scan at month 3 after receiving axicabtagene ciloleucel infusion at day 0. The negativity of PET/CT findings will be assessed according to Lugano Classification and Deauville criteria
Time frame: Month 3
Response month 3 central
The Complete Metabolic Response defined as negative findings on a PET/CT scan at month3 after receving axicabtagene ciloleucel infusion as assessed by central imaging review of PET/CT
Time frame: Month 3
Overall response rate
The Overall response rate (ORR) defined as the percentage of patients who achieved partial metabolic response (PMR) or complete metabolic response (CMR) according to the Lugano Classification criteria at month 3 determined by both central and investigator assessments.
Time frame: Month 3
Best objective response
Best objective response rate defined as the percentage of CMR + PMR determined by the investigator assessment among all patients between month 1 and month 12 from axicabtagene ciloleucel infusion
Time frame: 1 year
Best complete response rate
Best Complete Response rate defined as the percentage of CMR determined by the investigator assessment among all patients between month 1 and month 12 from axicabtagene ciloleucel infusion
Time frame: 1 year
Overall survival
The overall survival, defined as the time from inclusion to death from any cause. Alive patients will be censored at their last follow-up date.
Time frame: Up to 5 years
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Palma de Mallorca, Balearic Islands, Spain
Hospital Universitario Marqués de Valdecilla
Santander, Cantabria, Spain
RECRUITINGHospital Universitario de Salamanca
Salamanca, Castille and León, Spain
RECRUITINGHospital Universitari Vall d'Hebron
Barcelona, Catalonia, Spain
RECRUITINGHospital Clinic i Provincial de Barcelona
Barcelona, Catalonia, Spain
RECRUITINGInstitut Català d'oncologia de L'Hospitalet
L'Hospitalet de Llobregat, Catalonia, Spain
RECRUITINGHospital Universitario Donostia
San Sebastián, Gipuzkoa, Spain
RECRUITINGComplejo Hospitalario Universitario de Gran Canaria Dr. Negrín
Las Palmas de Gran Canaria, Las Palmas, Spain
RECRUITINGHospital General Universitario Gregorio Marañón
Madrid, Madrid, Spain
RECRUITING...and 5 more locations
Progression free survival
The Progresison Free Survival, defined as the time from axicabtagene ciloleucel infusion to the first observation of documented disease progression/relapse (based on investigator disease assessment (INV)) or death due to any cause. If a patient has not progressed or died, PFS will be censored at the time of last visit with adequate assessment
Time frame: Up to 5 years
Event Free Survival
Event-free survival (EFS), defined as the time between leukapheresis and to any event preventing axicabtagene ciloleucel infusion if axicabtagene ciloleucel is never infused, or death, disease progression, or instauration of a new lymphoma therapy for lymphoma progression after axicabtagene ciloleucel infusion. Patients without documented event at the time of analysis will be censored at the time of last visit with adequate assessment.
Time frame: Up to 5 years
Duration of Response
The Duration of Response (DOR), defined as the time from attainment of PMR or CMR to the date of first documented disease progression/relapse (based on investigator disease assessment) or death from any cause
Time frame: Up to 5 years
Duration of Complete Response
Duration of complete response (DoCR), defined as the time from achievement CMR to the date of first documented disease progression/relapse (based on investigator disease assessment) or death from any cause.
Time frame: Up to 5 years
Adverse events
Type, frequency and severity of adverse events (AEs) and serious adverse events (SAEs)
Time frame: Up to 4 weeks
AESIs
Incidence, severity and treatment of adverse events of special interest: Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), prolonged cytopenia and infections, hypogammaglobulinemia and emergent secondary malignancies.
Time frame: Up to 5 years
Quality of Life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
The EORTC QLQ-C30 is a 30-item questionnaire measuring cancer patients' physical, emotional, and social functioning. Scores range from 0 to 100. Range: 0 (worst) to 100 (best). Higher scores indicate better quality of life for functional scales and worse symptoms for symptom scales.
Time frame: Up yo 1 year
Quality of Life assessed using the EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L)
The EQ-5D-5L evaluates mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. It includes a visual analog scale (VAS) from 0 to 100. Range: 0 (worst imaginable health) to 100 (best imaginable health). Higher scores indicate better health status.
Time frame: Up to 1 year
Quality of Life assessed using the EORTC Quality of Life Questionnaire for High-Grade Non-Hodgkin Lymphoma (QLQ-NHL-HG29)
The QLQ-NHL-HG29 is a disease-specific module assessing symptoms and functioning in patients with high-grade non-Hodgkin lymphoma. Scores range from 0 to 100. Range: 0 to 100. Higher scores indicate worse symptoms or problems.
Time frame: Up to 1 year