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CCTL019J2101 - Portia

AcronymISRCTNEudraCTClinicaltrials.govDRKS
2018-000973-57

Phase Ib study of tisagenlecleucel in combination with pembrolizumab in relapsed/refractory (r/r) Diffuse Large Bcell Lymphoma (DLBCL) patients

Status: Active

Purpose / Objectives

Primary Outcome

  • Primary objective for the dose timing selection part is to assess the feasibility, safety and tolerability of administration of pembrolizumab following tisagenlecleucel infusion, and determine the optimal time to start pembrolizumab.
  • Primary objective for the dose expansion is to evaluate the anti-tumor activity of the combination of tisagenlecleucel and pembrolizumab using month 3 disease response rate as per Lugano criteria assessed by local investigator

Secondary Outcomes

  • Evaluate overall response rate as per Lugano criteria assessed by local
    investigator.
  • Evaluate duration of response as per Lugano criteria assessed by local
    investigator.
  • Evaluate progression free survival as per Lugano criteria assessed by local
    investigator.
  • Evaluate overall survival.
  • Evaluate the safety and tolerability of tisagenlecleucel in combination with
    pembrolizumab.
  • Characterize the in vivo cellular kinetics of tisagenlecleucel in blood, bone marrow, lymph nodes and other tissues if available by qPCR and flow cytometry.
  • Characterize the impact of pembrolizumab dosing strategy on the cellular kinetics of tisagenlecleucel.
  • Characterize the pembrolizumab pharmacokinetics in r/r DLBCL patients who received tisagenlecleucel.
  • Characterize immunogenicity (cellular and humoral) of tisagenlecleucel and impact on cellular kinetics, efficacy and safety

Diagnosis

DLBCL, Relapsed or refractory disease after anti-CD20 and anthracycline based chemotherapy, and either having progressed after (or relapsed after) ASCT or being ineligible for or not consenting to ASCT

Patient attributes

Age

18-99

Inclusion criteria

  • Confirmed DLBCL as per the local histopathological assessment
  • Relapsed or refractory disease after anti-CD20 and anthracycline based chemotherapy, and either having progressed after (or relapsed after) ASCT, or being ineligible for or not consenting to ASCT
  • Measurable disease at time of enrollment (see Protocol)
  • Adequate organ function (see Protocol)
  • Must have a leukapheresis product of non-mobilized cells accepted for manufacturing
  • [...]

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.
  • Treatment with any prior gene therapy product
  • 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
  • Presence of active or prior hepatitis B or C as indicated by serology
  • HIV positive patients.
  • 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 diseases including.... (see Protocol)
  • Intolerance to the excipients of the tisagenlecleucel cell product
  • Patients with history of or active neurological auto immune or inflammatory disorders (e.g.Guillain-Barré Syndrome, Amyotrophic Lateral Sclerosis, and myastenia gravis)
  • 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 severe hypersensitivity reactions to other monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction.
  • History of interstitial lung disease or (non-infectious) pneumonitis that required oral or intravenous steroids (other than COPD exacerbation) or current pneumonitis.
  • [...]

Trial design

  • Phase I
  • Multicenter
  • Prospective
  • One-arm
  • Open Label

Intervention

CTL019, tisagenlecleucel. The recommended dose will consist of a single
intravenous infusion of 0.6 – 6.0 x 108 CAR-positive viable T cells.
Pembrolizumab dosage will be 200mg, administered intravenously over 30 minutes every 3 weeks for up to 6 doses.

Documents (password protected)

Responsibilities in overall trial

Novartis Pharma GmbH

  • Tel. 0911 2730
  • Fax 0911 27312683

National Coordinating Investigator

Prof. Dr. med. Peter Borchmann

Study Sites

Klinik I für Innere Medizin

Study office

  • Klinisches Studienzentrum der Klinik I für Innere Medizin Köln

Status

Active

Principal Investigator

Prof. Dr. med. Peter Borchmann

Deputy of Principal Investigator

  • PD Dr. Dr. med. Udo Holtick

Subinvestigator

  • Dr. Philipp Gödel

Contact at Site