Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as tisagenlecleucel, CART-19, CTL019, Kymriah, Tisagenlecleucel-T, Tisa-cel
CTL019 T-cells · 13 trials · 14 indications
Progression free survival (PFS) based on Lugano response criteria, defined as time from randomization to the first of the following events to occur: * progressive disease (by BIRC) * death from any cause
Percentage of participants with Serious AEs (SAEs) and non-SAEs
Treatment emergent adverse events were collected from CTL019 infusion until end of study, up to 12 months
DFS is defined as the time from the date of tisagenlecleucel infusion to the date of the first documented morphological relapse, occurrence of secondary malignancy or death due to any cause. Participants are not censored at the start of subsequent anticancer therapy or SCT while in remission.
OS is defined as the time from date of first tisagenlecleucel infusion to the date of death due to any reason.
The overall response rate (ORR) is defined as the percentage of subjects with a best overall disease response of complete response (CR) or partial response (PR), where the best overall disease response is defined as the best disease response recorded from tisagenlecleucel infusion until progressive disease or start of new anticancer therapy, whichever comes first.
Complete response rate was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) recorded from tisagenlecleucel infusion until progressive disease or start of new anticancer therapy, whichever came first. CRR was determined by an independent review committee (IRC) and was based on Lugano 2014 classification response criteria. The radiological response is first obtained from CT and PET studies according to the Lugano 2014 criteria. CT response is based on anatomical measurements of index/non-index/new lesions and spleen length. The possible response outcomes are complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). PET response based on a 5-point scale (5PS) or Deauville score. The possible outcomes for PET response are complete metabolic response (CMR), partial metabolic response (PMR), no metabolic response (NMR), or progressive metabolic disease (PMD).
ORR, which includes complete response (CR) and partial response (PR) in the Main cohort as determined by IRC assessment. ORR is the percentage of participants with a best overall disease response of CR or PR, where the best overall disease response is defined as the best disease response recorded from CTL019 infusion until progressive disease or start of new anticancer therapy (including ASCT), whichever comes first. Response was assessed according to Evaluation Criteria in diffuse large B cell lymphoma studies (based on Cheson Response criteria and the Lugano Classification (2014))
Evaluating the efficacy of tisagenlecleucel therapy from all manufacturing facilities as measured by overall remission rate (ORR) during the 3 months after tisagenlecleucel administration. ORR included complete response (CR) and CR with incomplete blood count recovery (CRi) as determined by an Independent Review Committee assessment. Per response criteria defined by National Comprehensive Cancer Network (NCCN), American Society of Hematology (ASH) and International Working Group (IWG) guidelines. CR is defined as: Bone marrow \<5% blasts, Peripheral blood: Neutrophils \>1.0 x 10\^9/L, and Platelets \>100 x 10\^9/L and Circulating blasts \<1% and No evidence of extramedullary disease, at least 7 days transfusion independency. CRi is defined as all the prior criteria being met, except that the following exists: Neutrophils ≤1.0 x 10\^9/L, and/or Platelets ≤100 x 10\^9/L, and/or Platelet and/or neutrophil transfusions ≤7 days before the date of the peripheral blood sample for disease assessment.
ORR is defined as the percentage of participants with a best overall disease response of complete remission (CR) or Complete remission with incomplete blood count recovery (CRi), where the best overall disease response is defined as the best disease response recorded from CTL019 infusion until the start of new anticancer therapy. Best response was assigned in the following order: CR, CRi, CR or CRi with residual mediastinal disease, No response and Unknown.
Overall Remission Rate (ORR), which includes Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi), as determined by assessments of peripheral blood, bone marrow, CNS symptoms, physical exam (PE) and cerebrospinal fluid (CSF). This primary endpoint was based on the local investigator assessment. No participants with lymphoblastic lymphoma were infused in this study.
Adverse events will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Cytokine release syndrome and immune effector cell associated neurotoxicity syndrome are graded using American Society for Transplantation and Cellular Therapy (ASTCT) Consensus grading.
Will define the dose as the RP2D for which the isotonic estimate of the toxicity rate is closest to the targeted toxicity rate (i.e., 25%). If there is a tie, the higher dose level when the isotonic estimate is lower than the targeted toxicity rate; and will choose the lower dose level when the isotonic estimate is greater than the targeted toxicity rate.
Will estimate fold-change increase in CD27/CD28 double positive T cells following in vivo exposure to duvelisib using multiparametric flow cytometry.
| Arm | Type | Description |
|---|---|---|
| Tisagenlecleucel | EXPERIMENTAL | Participants randomized to the tisagenlecleucel treatment strategy will receive a single infusion of 0.6 to 6 x 10\^8 CAR-positive viable T-cells |
| R2 or R-CHOP | ACTIVE_COMPARATOR | Participants randomized to Standard of Care treatment will receive either R2 or R-CHOP based on investigator choice of therapies, and this has to be determined prior to randomization. |
| Group A: pALL | EXPERIMENTAL | Pediatric/young adult patients with r/r pALL who meet the indication in the Health Authority-approved CTL019 package insert in the respective country/region whose final manufactured product is OOS for commercial release, but it is considered that the benefit-risk profile may remain favorable and the usual expected benefits of infusing such a product outweigh the potential risks for the patient. |
| Group B: r/r LBCL | EXPERIMENTAL | Adult patients with r/r LBCL including DLBCL not otherwise specified, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma, that is consistent with the Health Authority-approved indication in the package insert for CTL019 in the respective country/region whose final manufactured product is OOS for commercial release, but it is considered that the benefit-risk profile may remain favorable and the usual expected benefits of infusing such a product outweigh the potential risks for the patient. |
| Group C: r/r NHL | EXPERIMENTAL | Adult patients with r/r NHL in consistent with the Health Authority approved indication in the package insert for CTL019 in Japan whose final manufactured product is OOS for commercial release, but it is considered that the benefit-risk profile may remain favorable and the usual expected benefits of infusing such a product outweigh the potential risks for the patient. |
| CTL019 | EXPERIMENTAL | CTL019 transduced T cells were given as a single dose of 0.2 to 5.0 × 10\^6 autologous CTL019 transduced viable T cells per kg body weight (for patients ≤ 50 kg) and 0.1 to 2.5 × 10\^8 CTL019 transduced viable T cells (for patients \> 50 kg) |
| Single dose of CTL019 | EXPERIMENTAL | Based on the subject's weight one of two possible dose ranges will be prepared for the subject: Subjects ≤ 50 kg: 0.2 to 5.0 x 10(6) CAR-positive viable T cells per kg body weight OR Subjects \> 50 kg: 0.1 to 2.5 x 10(8) CAR-positive viable T cells |
| tisagenlecleucel (CTL019) | EXPERIMENTAL | Pediatric patients with relapsed/refractory B-cell ALL |
| Treatment (TBI, lymphodepletion, Tisa-cel) | EXPERIMENTAL | Patients undergo leukapheresis and receive lymphodepleting chemotherapy with cyclophosphamide IV and fludarabine IV on days -5 to -3 per standard of care. Patients also undergo low dose TBI on day -2 and receive standard of care Tisa-cel IV over 5-30 minutes on day 0. Additionally, patients undergo blood sample collection, PET/CT or CT throughout the study. |
| Tisagenlecleucel+Pembrolizumab | EXPERIMENTAL | - |
| Treatment (duvelisib) | EXPERIMENTAL | Patients receive duvelisib PO BID for 2 weeks prior to collection of CAR-T cells in the absence of disease progression or unacceptable toxicity. Patients then receive tisagenlecleucel via infusion. |
| Name | Type | Description |
|---|---|---|
| Tisagenlecleucel | BIOLOGICAL | Tisagenlecleucel is a solution for infusion of 0.6 to 6 x 10\^8 CAR-positive viable T-cells taken intravenously (i.v.). |
| Lenalidomide and rituximab (R2) in 28-day cycles for up to 12 cycles. | DRUG | Lenalidomide 20 mg daily on days 1-21 for up to 12 cycles Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 2-5 |
| Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone or prednisolone (R-CHOP) in 21-day cycles for 6 to 8 cycles | DRUG | Rituximab 375 mg/m2 i.v. on day 1 Cyclophosphamide 750 mg/m2 i.v. day 1 Doxorubicin 50 mg/m2 i.v. day 1 Vincristine 1.4 mg/2 (capped at 2 mg) i.v. day 1 Prednisone or prednisolone 40 mg/m2 PO days 1-5 |
| Lymphodepleting chemotherapy | DRUG | Fludarabine (25 mg/m\^2 intravenously \[i.v.\] daily for 3 doses) OR Cyclophosphamide (250 mg/m\^2 i.v. daily for 3 doses starting with the first dose of fludarabine). OR Bendamustine 90 mg/m\^2 i.v. daily for 2 days (If there was previous grade IV hemorrhagic cystitis with cyclophosphamide, or the participant demonstrated resistance to a previous cyclophosphamide-containing regimen) |
| Corticosteroids and/or Radiation (Bridging therapy) | OTHER | Corticosteroids and/or Radiation |
| CTL019 | BIOLOGICAL | A single intravenous (i.v.) infusion of CAR-positive viable T cells. |
| Bridging Therapy | DRUG | Pre-treatment phase could also include bridging therapy of investigator's choice |
| CTL019 T-cells | BIOLOGICAL | A target dose of CTL019 transduced cells will consist of a single infusion of 2.0 to 5.0 x 10\^6 CTL019 transduced cells per kg body weight (for patients ≤ 50 kg) and 1.0 to 2.5 x 10\^8 CTL019 transduced viable T cells (for patients \> 50 kg). The following cell dose ranges may be infused if all other safety release criteria are met: 0.2 to 5.0 x 10\^6 CTL019 transduced viable T cells per kg body weight (for patient ≤ 50 kg) and 0.1 to 2.5 x 10\^8 CTL019 transduced viable T cells (for patients \> 50 kg). |
| Biospecimen Collection | PROCEDURE | Undergo blood sample collection |
| Computed Tomography | PROCEDURE | Undergo PET/CT or CT |
| Cyclophosphamide | DRUG | Given IV |
| Fludarabine | DRUG | Given IV |
| Leukapheresis | PROCEDURE | Undergo leukapheresis |
| Positron Emission Tomography | PROCEDURE | Undergo PET/CT |
| Total-Body Irradiation | RADIATION | Undergo low dose TBI |
| Pembrolizumab | DRUG | anti PD-1 |
| Duvelisib | DRUG | Given PO |
Inclusion Criteria: 1. Age ≥ 18 years at the date of signing the informed consent form. 2. Follicular lymphoma grade 1, 2, or 3A confirmed histologically after latest relapse (local assessment). 3. Relapsed or refractory disease after a second or later line of systemic therapy including an anti-CD2...
CTL019 T-cells is an investigational cell therapy developed by Novartis AG for B-cell acute lymphoblastic leukemia. It is being studied in pediatric patients with relapsed or refractory B-cell ALL. The program has completed one Phase 2 clinical trial in the United States.
CTL019 T-cells is being studied for B-cell acute lymphoblastic leukemia, including relapsed and refractory forms of the disease. The completed Phase 2 trial enrolled pediatric patients aged 3 years and older. It is an investigational therapy and is not established as an approved treatment.
CTL019 T-cells is being developed by Novartis AG, which trades under the ticker NVS. Novartis sponsored the Phase 2 study of the therapy in pediatric patients with B-cell acute lymphoblastic leukemia. The program is part of the company's oncology pipeline.
CTL019 T-cells is in Phase 2 development. One Phase 2 trial has been completed, and no trials are currently active. The study was an uncontrolled, non-randomized trial that enrolled 75 pediatric patients with B-cell acute lymphoblastic leukemia.
CTL019 T-cells has been studied in one completed Phase 2 trial, NCT02228096, titled Study of Efficacy and Safety of CTL019 in Pediatric ALL Patients. The trial enrolled 75 patients in the United States with relapsed or refractory B-cell acute lymphoblastic leukemia and included patients aged 3 years and older.
The Phase 2 trial of CTL019 T-cells, NCT02228096, was an uncontrolled, non-randomized study with no double-blind design. It enrolled 75 pediatric patients with B-cell acute lymphoblastic leukemia across sites in the United States. The study has been completed.