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De klinische studie NCT07502118 (NexCAR19) voor Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia (B-ALL), Gerecidiveerde/refractaire non-Hodgkin-lymfoom, Diffuus Groot B-cel Lymfoom (DLBCL), Hooggradig B-cel lymfoom (HGBCL), Folliculair lymfoom (FL) is rekruterend. Bekijk de kaartweergave van de Klinische Studies Radar en de AI-ontdekkingstools voor alle details. Of stel hier een vraag. | ||
NexCAR19 (Talikabtagene Autoleucel) in Relapsed/Refractory B-Cell Malignancies (NexCAR19) Fase 2, Fase 3 40 Open-label Algehele overleving
An Open-Label, Multicenter Phase 2-3 Clinical Study of Anti-CD19 Chimeric Antigen Receptor T Cells (Talikabtagene Autoleucel) in Patients With Relapsed/Refractory B-Cell Malignancies (NexCAR19)
- NexCAR19
- TSB-NexCar19
Fase 3
B-Cell Acute Lymphoblastic Leukemia (B-ALL)
Non-Hodgkin Lymphoma
High-Grade Lymphoma
Low-Grade Lymphoma
CD19
CAR-T Cell Therapy
Talikabtagene Autoleucel
Autologous T Cells
Adoptive Cell Therapy
Cytokine Release Syndrome (CRS)
ICANS
| Deelnemersgroep/Studiearm | Interventie/Behandeling |
|---|---|
ExperimenteelSingle Arm - Open Label Study Talikabtagene Autoleucel (NexCAR19) CAR-T Cell Therapy | Talikabtagene Autoleucel Talikabtagene Autoleucel is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy. Peripheral blood mononuclear cells are collected via leukapheresis, genetically modified to express an anti-CD19 CAR, expanded ex vivo, and infused intravenously after lymphodepleting chemotherapy. |
| Uitkomstmaat | Beschrijving van de uitkomstmaat | Tijdsbestek |
|---|---|---|
Overall Response Rate (ORR) to CD19 CAR-T cell product at Day 28 post-infusion | Evaluation of Overall Response Rate (ORR) at Day 28 following infusion of the CD19 CAR-T cell product:
In patients with relapsed/refractory (r/r) B-ALL, response will be assessed by morphological bone marrow (BM) analysis at Day 28, and minimal residual disease (MRD) will be evaluated using flow cytometry.
In patients with relapsed/refractory (r/r) B-cell lymphoma, treatment response will be assessed by PET/CT according to the Lugano criteria.
Duration of Response (DoR):
Defined as the time from the date of first documented response to the date of disease progression or death, whichever occurs first. | Day 28 post-infusion |
| Uitkomstmaat | Beschrijving van de uitkomstmaat | Tijdsbestek |
|---|---|---|
Complete Remission (CR) Rate | The proportion of participants achieving complete remission following CAR-T cell infusion.
For participants with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), response will be assessed by morphological bone marrow evaluation and minimal residual disease (MRD) assessment using flow cytometry.
For participants with relapsed/refractory B-cell lymphoma, response will be assessed by PET/CT according to the Lugano classification criteria.
Unit of Measure:
Percentage of participants | Day 90 and Day 180 after CAR-T cell infusion |
Overall Response Rate (ORR) | The proportion of participants achieving an overall response following CAR-T cell infusion. ORR includes complete response (CR), complete response with incomplete hematologic recovery (CRi), and partial response (PR).
For participants with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), response will be assessed by morphological bone marrow evaluation and minimal residual disease (MRD) assessment using flow cytometry.
For participants with relapsed/refractory B-cell lymphoma, response will be assessed by PET/CT according to the Lugano classification criteria.
Unit of Measure:
Percentage of participants | Day 90 and Day 180 after CAR-T cell infusion |
Incidence of Cytokine Release Syndrome (CRS) and associated serum cytokine profile within 10 days post-infusion | Evaluation of serum cytokine profile within the first 10 days following CAR-T infusion to assess its association with the development of CRS. | Within 10 days post-infusion |
Incidence and duration of B-cell lymphopenia and hypogammaglobulinemia | Assessment of the incidence and duration of B-cell lymphopenia (BCL) and hypogammaglobulinemia, and evaluation of their correlation with maintenance of complete response. | Up to 2 years post-infusion |
Proportion of participants with sustained disease control at Year 1 and Year 2 post CAR-T infusion | Sustained disease control is defined as the absence of progressive disease and no requirement for additional anti-leukemic or anti-lymphoma therapy. In patients with relapsed/refractory B-ALL, disease status will be assessed by morphological bone marrow evaluation and minimal residual disease (MRD) analysis using flow cytometry. In patients with relapsed/refractory B-cell lymphoma, disease status will be assessed by PET/CT according to Lugano criteria. The reported value will be the proportion of participants maintaining disease control at each time point.
Unit of Measure:
Percentage of participants | 1 year and 2 years post-infusion |
Persistence of CAR-T Cells in Peripheral Blood Assessed by Transgene Copy Number Using Quantitative Real-Time PCR (qPCR) | Description In vivo persistence of infused CAR-T cells will be quantified in peripheral blood using transgene detection by quantitative real-time PCR (qPCR). Results will be reported as the number of transgene copies per µg of genomic DNA and summarized longitudinally for each participant.
Unit of Measure Transgene copies per µg genomic DNA | Up to 2 years post-infusion |
Expansion of CAR-Expressing T Cells in Peripheral Blood Assessed by Flow Cytometry | Description Expansion of infused CAR-T cells will be evaluated in peripheral blood using flow cytometry. Results will be reported as the percentage of CAR-positive (CAR+) T cells among the total T-cell population.
Unit of Measure Percentage of CAR+ T cells | Up to 2 years post-infusion |
Overall Survival (OS) at Year 1 and Year 2 post CAR-T infusion | OS is defined as the time from study enrollment to death from any cause. Participants alive at the time of analysis will be censored. Reported values will be the proportion of participants surviving at each time point.
Unit of Measure: Percentage of participants | 1 year and 2 years post-infusion |
Event-Free Survival (EFS) at Year 1 and Year 2 post CAR-T infusion | EFS is defined as the time from study enrollment to the earliest occurrence of disease progression, death, or initiation of new therapy. Reported values will be the proportion of participants event-free at each time point.
Unit of Measure: Percentage of participants | 1 year and 2 years post-infusion |
Progression-Free Survival (PFS) at Year 1 and Year 2 post CAR-T infusion | PFS is defined as the time from study enrollment to disease progression, relapse, or death from any cause. Disease progression will be assessed by PET/CT for lymphoma or bone marrow morphology for B-ALL. Reported values will be the proportion of participants progression-free at each time point.
Unit of Measure: Percentage of participants | 1 year and 2 years post-infusion |
Relapse-Free Survival (RFS) at Year 1 and Year 2 post CAR-T infusion | RFS is defined as the time from study enrollment to disease relapse or death from any cause. Reported values will be the proportion of participants relapse-free at each time point.
Unit of Measure: Percentage of participants | 1 year and 2 years post-infusion |
All participants must meet Inclusion Criteria 1-13.
Additionally:
High-grade lymphoma subjects must meet Criteria 14-18.
Other B-cell lymphoma subjects must meet Criteria 19-24.
B-ALL subjects must meet Criteria 25-29.
General Inclusion Criteria (Applicable to All Cohorts)
Age ≥18 years.
Patients approved for leukapheresis by the CAR-T cell treatment council.
ECOG performance status <2.
Life expectancy ≥12 weeks.
Renal Function: Estimated creatinine clearance ≥60 mL/min (Cockcroft-Gault) → fludarabine/cyclophosphamide lymphodepletion.
In lymphoma cohort patients with creatinine clearance 30-60 mL/min, bendamustine may be used as an alternative due to cumulative fludarabine toxicity and neurotoxicity risk.
Liver Function:
- ALT and AST ≤3 × ULN unless attributable to underlying malignancy.
- Total bilirubin ≤2 × ULN except in Gilbert syndrome, isolated unconjugated hyperbilirubinemia, or if attributable to underlying malignancy.
Hemodynamically stable with LVEF ≥45% (confirmed by echocardiography or MUGA scan).
Baseline oxygen saturation >92% on room air.
ANC ≥500/µL (may be waived if cytopenia due to underlying malignancy at investigator discretion).
Platelet count ≥50,000/µL (may be waived if cytopenia due to underlying malignancy at investigator discretion).
Negative serum or urine pregnancy test (within 24 hours prior to conditioning therapy) in women of childbearing potential; also negative prior to leukapheresis.
Sexually active patients (women of childbearing potential and all men) must use highly effective contraception for ≥12 months after CAR-T infusion.
Written informed consent provided.
High-Grade Lymphoma - Additional Inclusion Criteria (14-18)
Histologically confirmed previously treated:
- Diffuse large B-cell lymphoma (DLBCL)
- Primary mediastinal B-cell lymphoma
- Transformed indolent B-cell lymphoma
- Follicular lymphoma Grade 3B
- High-grade B-cell lymphoma
Chemotherapy-refractory disease defined as:
- Primary refractory disease
- Best response to last chemotherapy = PD or SD (biopsy confirmed)
- Progression/relapse ≤12 months after autologous SCT
- Relapse ≤12 months after first-line CR (biopsy confirmed)
- Relapse beyond 12 months if auto-SCT not feasible
Not eligible for or unwilling to undergo autologous SCT.
Must have received anti-CD20 monoclonal antibody and anthracycline-containing regimen. Transformed lymphoma subjects must have received ≥2 prior systemic lines.
Measurable disease per International Working Group (IWG) criteria.
Other B-Cell Lymphomas - Additional Inclusion Criteria (19-24)
Histologically confirmed:
- Mantle Cell Lymphoma (Cyclin D1 overexpression or t(11;14))
- Follicular Lymphoma Grade I-IIIA
- Marginal Zone Lymphoma
Relapsed or refractory disease:
MCL: ≤5 prior regimens including:
- Anthracycline or bendamustine
- Anti-CD20 antibody
- BTK inhibitor (ibrutinib or acalabrutinib; intolerance allowed)
FL/MZL: Progression after ≥2 combination chemoimmunotherapy regimens (single-agent CD20 or splenectomy not counted).
Radiologically measurable disease at screening
- per revised IWG (Cheson 2007): ≥1 measurable lesion
- Previously irradiated lesions measurable only if progression documented
- If only nodal disease: ≥1 node ≥2 cm
No known active CNS lymphoma involvement.
Prior therapy toxicities resolved to ≤Grade 1 (except alopecia).
Prior autologous HCT, POD24 status, and prior PI3K inhibitor therapy allowed.
B-Cell Acute Lymphoblastic Leukemia (B-ALL) - Additional Inclusion Criteria (25-29)
Relapsed/Refractory B-ALL meeting one of:
Primary refractory disease
First relapse ≤12 months
≥2 prior systemic lines
Post-allogeneic SCT relapse (≥100 days post-transplant; off immunosuppression ≥4 weeks)
Ph+ disease:
- TKI intolerance
- Relapsed/refractory after ≥2 TKIs
- No alternative TKI option
Ineligible for allogeneic SCT due to
- comorbidity,
- conditioning contraindication,
- no donor,
- prior SCT,
- or refusal (documented).
Morphological bone marrow disease.
CD19 tumor expression documented within 3 months (BM or PB by flow cytometry).
Absolute lymphocyte count ≥100/µL.
≥3 half-lives elapsed since prior immune checkpoint inhibitor or stimulatory therapy
All participants must meet Exclusion Criteria 1-14.
Additionally:
High-grade lymphoma: 15-22
Low-grade lymphoma: 23-24
B-ALL: 25
General Exclusion Criteria (All Cohorts)
Uncontrolled life-threatening infection (e.g., positive blood culture ≤72h before infusion).
HIV positive.
Active HBV replication or active HCV (RNA positive).
Unstable angina or MI within 6 months.
Uncontrolled cardiac arrhythmia.
Concurrent malignancy except adequately treated non-melanoma skin cancer, in situ carcinoma (≥3 years disease-free), or completely resected malignancy in CR ≥3 years.
Pregnant or breastfeeding.
Hypersensitivity to CAR-T product excipients.
Active autoimmune/inflammatory neurologic disorders.
Primary immunodeficiency.
Short-acting leukemia/lymphoma therapies must be stopped >72h before leukapheresis and infusion.
Burkitt lymphoma/leukemia.
Steroids must be discontinued >72h prior (<12 mg/m²/day hydrocortisone equivalent allowed).
Investigator deems subject unable to comply.
High-Grade Lymphoma - Additional Exclusion (15-22)
Active CNS involvement.
Prior allogeneic HSCT.
Systemic immunosuppressives not discontinued ≥1 weeks before leukapheresis/infusion.
Anti-proliferative therapy not stopped ≥1 weeks prior.
Cytotoxic drugs not stopped ≥1 week prior.
A minimum interval of ≥4 weeks is required between donor lymphocyte infusion (DLI) and leukapheresis, and ≥4 weeks between DLI and CAR-T cell infusion. This requirement applies to prior antibody-based therapies, including anti-CD20, anti-CD22, anti-CD79a, and similar agents.
CNS prophylaxis not stopped >1 week prior.
Radiation not stopped ≥2 days before leukapheresis and ≥1 week before infusion.
Low-Grade Lymphoma - Additional Exclusion (23-24)
Live vaccine ≤6 weeks before conditioning.
Tumor mass effect requiring urgent treatment.
B-ALL - Additional Exclusion (25)
Acute graft-versus-host disease (GVHD) of Grade II-IV according to the Glucksberg criteria or Grade B-D according to the IBMTR index; or acute or chronic GVHD requiring systemic treatment within 4 weeks prior to enrollment.
Health Institutes of Turkey