Study of Tisagenlecleucel in Combination With Pembrolizumab in r/r Diffuse Large B-cell Lymphoma Patients

Study Overview
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Brief Summary
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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.

Official Title
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Phase Ib Study of Tisagenlecleucel in Combination With Pembrolizumab in Relapsed/Refractory (r/r) Diffuse Large B-cell Lymphoma (DLBCL) Patients.

Conditions
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Diffuse Large B-cell Lymphoma

Intervention / Treatment
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* Biological: Tisagenlecleucel
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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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/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tisagenlecleucel+Pembrolizumab<br> | Biological: Tisagenlecleucel<br>* Gene modified autologous T cells<br>* Other names: CTL019;Drug: Pembrolizumab<br>* anti PD-1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) |  | 24 months | 
| Progression Free Survival (PFS) |  | 24 months | 
| Overall Survival (OS) |  | 24 months | 
| In vivo cellular kinetics of tisagenlecleucel in blood, bone marrow, lymph nodes and other tissues by qPCR and flow cytometry |  | 24 months | 
| Impact of pembrolizumab dosing strategy on the cellular kinetics of tisagenlecleucel by qPCR and flow cytometry |  | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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