Diffuse Large B-cell Lymphoma
Conditions
Keywords
Lymphoma tisagenlecleucel, Diffuse Large B-cell Lymphoma, CTL019, PORTIA, DLBCL, tisagenlecleucel, pembrolizumab, r/r Diffuse large B-cell Lymphoma, relapsed/refractory Diffuse large B-cell Lymphoma
Brief summary
A multi-center, open-label, phase Ib study to evaluate the safety and efficacy of the administration of tisagenlecleucel in combination with pembrolizumab in patients with r/r DLBCL who have received 2 or more lines of systemic therapy, including an anti-CD20 and anthracycline based chemotherapy and having failed to or are not candidates for ASCT. The study will consist of 2 parts: dose timing selection part and expansion part.
Interventions
BIOLOGICALTisagenlecleucel
Gene modified autologous T cells
DRUGPembrolizumab
anti PD-1
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
None (Open label)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed DLBCL per local histopathology assessment. * Relapsed or refractory disease after having recieved 2 or more lines of systemic therapy, including anti-CD20 and anthracycline based chemotherapy, and either having progressed after (or relapsed after) ASCT, or being not candidates for or not consenting to ASCT. * Measurable disease at time of enrollment * ECOG performance status that is either 0 or 1 at screening.
Exclusion criteria
* Patients with Richter's transformation, and Burkitt lymphoma, and primary DLBCL of CNS. * Prior treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy. * Patients with active CNS involvement are excluded, except if the CNS involvement has been effectively treated and provided that local treatment was \>4 weeks before enrollment. * Prior allogeneic HSCT. * Unstable angina and/or myocardial infarction and/or coronary artery bypass graft (CABG), or stroke within 6 months prior to screening, and/or impaired cardiac function or clinically significant cardiac disease * Patients with a history of prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibodies, other immune checkpoint inhibitors. * History of interstitial lung disease or (non-infectious) pneumonitis that required oral or intravenous steroids (other than COPD exacerbation) or current pneumonitis. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent of participants recieving pembrolizumab per protocol schedule | 21 days after first pembrolizumab infusion |
| Dose Timing part: Incidence of dose limiting toxicities (DLTs) | 21 days after first pembrolizumab infusion |
| Expansion part: Overall response rate (ORR) | 3 month post tisagenlecleucel infusion |
Secondary
| Measure | Time frame |
|---|---|
| In vivo cellular kinetics of tisagenlecleucel in blood, bone marrow, lymph nodes and other tissues by qPCR and flow cytometry | 24 months |
| Duration of Response (DOR) | 24 months |
| Immunogenicity measured by antibody titres specific to tisagenlecleucel molecule and by the presence of T lymphocytes activated by the tisagenlecleucel protein | 24 months |
| Impact of pembrolizumab dosing strategy on the cellular kinetics of tisagenlecleucel by qPCR and flow cytometry | 24 months |
| Progression Free Survival (PFS) | 24 months |
| Overall Survival (OS) | 24 months |
Countries
Austria, Canada, United States
Outcome results
None listed