Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Tisagenlecleucel · 7 trials · 10 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
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))
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.
| 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. |
| CTL019 | EXPERIMENTAL | All patients who received tisagenlecleucel infusion. |
| 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 | - |
| 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 |
| Bridging Therapy | DRUG | Pre-treatment phase could also include bridging therapy of investigator's choice |
| 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 |
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...
Tisagenlecleucel is an investigational cell therapy being studied for use in several blood cancers, including Diffuse Large B-cell Lymphoma, Recurrent Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, Non-Hodgkin Lymphoma, and Primary CNS Lymphoma. It is currently in Phase 1 clinical development for these oncology indications.
Tisagenlecleucel is being developed by Novartis AG, a company traded on the stock exchange under the ticker symbol NVS. The drug is a monoclonal antibody modality classified as a -cel (cell therapy) product.
Tisagenlecleucel is currently in Phase 1 clinical development. It is an investigational drug and has not been approved by regulatory authorities. The drug is being studied in clinical trials for multiple lymphoma indications, including Diffuse Large B-cell Lymphoma and Follicular Lymphoma.
Tisagenlecleucel has been studied in several clinical trials. NCT02445248 evaluated its efficacy and safety in adult DLBCL patients with 115 participants. NCT03568461 studied it in refractory or relapsed Follicular Lymphoma with 98 participants. NCT03610724 examined it in pediatric Non-Hodgkin Lymphoma patients with 34 participants. NCT07676877 is a Phase 1 trial in Recurrent Diffuse Large B-Cell Lymphoma with 18 participants.
Yes, Tisagenlecleucel is also known as CTL019. The clinical trial NCT02445248, titled 'Study of Efficacy and Safety of CTL019 in Adult DLBCL Patients', uses this alternative name to refer to the same investigational drug developed by Novartis.