Study of Tisagenlecleucel in Chinese Adult Patients With Relapsed or Refractory Diffuse Large B-cell Non-Hodgkin Lymphoma (DLBCL)

A Phase II, Single-arm, Multicenter Trial to Evaluate the Efficacy and Safety of Tisagenlecleucel in Chinese Adult Patients With Relapsed or Refractory Diffuse Large B-cell Non-Hodgkin Lymphoma (DLBCL)

This is a multi-center, phase II study to evaluate the efficacy and safety of CTL019 in Chinese adult patients with relapsed or refractory DLBCL.

Study Overview

• Status: Withdrawn
• Conditions: Diffuse Large B-Cell Lymphoma (DLBCL)
• Intervention / Treatment: Biological: Tisagenlecleucel

Detailed Description

Disease assessments will be performed at screening, after bridging, 1, 3, 6, 9 and 12 months after tisagenlecleucel infusion, and every 6 months in the second year, and annually up to 60 months after infusion. Efficacy will be assessed until progression; safety will be assessed throughout the study. A long term follow-up up to 15 years after CTL019 infusion will continue under a separate protocol (CCTL019A2205B)(NCT02445222).

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed informed consent must be obtained prior to participation in the study
2. Patients must be ≥18 years of age at the time of ICF signature
3. Histologically confirmed DLBCL at last relapse (including DLBCL transformed from follicular lymphoma and double-triple hit lymphoma)
4. Relapsed or refractory disease after at least 2 lines of systemic therapy, including anti-CD20 antibody and an anthracycline, or having failed or being ineligible for autologous HSCT
5. ECOG performance status that is either 0 or 1 at screening

6. Measurable disease at time of enrollment:

   • Nodal lesions greater than 15 mm in the long axis, regardless of the length of the short axis or
   • Extra nodal lesion (outside lymph node or nodal mass, but including liver and spleen) at least 10 mm in long and short axis
7. Adequate organ function
8. Must have a leukapheresis material of non-mobilized cells available for manufacturing

Exclusion Criteria:

1. Prior treatment with anti-CD19 therapy, adoptive T cell therapy, or any prior gene therapy product
2. Primary mediastinal large B-cell lymphoma, EBV+ DLBCL, Richter's transformation, Burkitt lymphoma, primary DLBCL of CNS, T cell / histiocyte rich large B-cell lymphoma, primary cutaneous DLBCL.
3. Eligible for and consenting to autologous HSCT
4. Prior allogeneic SCT
5. Active CNS involvement by disease under study, except if the CNS involvement has been effectively treated (i.e. patient is asymptomatic) and local treatment was greater than 4 weeks before enrollment
6. Active neurological autoimmune or inflammatory disorders (e.g. Guillain-Barre syndrome)
7. Investigational medicinal product within the last 30 days or five half-lives (whichever is longer) prior to screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tisagenlecleucel; All patients eligible for treatment with tisagenlecleucel will receive a single dose of tisagenlecleucel.	Biological: Tisagenlecleucel; A single intravenous (i.v.) infusion of 0.6 - 6.0×10^8 CAR positive viable T cells.; Other Names: CTL019

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Complete Response (CR) and Partial Response (PR) according to the Lugano classification as determined by the Investigator.	From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	Time from CR or PR, whichever occurs first, to relapse or death due to DLBCL.	From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
Time to response (TTR)	Time from tisagenlecleucel infusion to CR or PR, whichever occurs first.	From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
Progression-Free Survival (PFS)	Time from tisagenlecleucel infusion to the first documented disease progression or death due to any cause.	From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
Event free survival (EFS)	Time from tisagenlecleucel infusion to the first documented disease progression or relapse, new treatment for lymphoma or death due to any cause.	From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
Overall Survival (OS)	Time from tisagenlecleucel infusion to death due to any cause.	From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
Number of Participants with On-Treatments Adverse Events, Serious Adverse Events, and Deaths	Analysis of absolute and relative frequencies for treatment emergent AE, SAE and Deaths by primary System Organ Class (SOC) through the monitoring of relevant clinical and laboratory safety parameters.	From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
Tisagenlecleucel immunogenicity (humoral)	The humoral immunogenicity assay will be evaluated to measure the antibody titers specific to the tisagenlecleucel molecule prior to and following infusion.	Up to Month 60
Tisagenlecleucel immunogenicity (cellular)	The cellular immunogenicity assay will be evaluated to assess the presence of T lymphocytes activated by the tisagenlecleucel protein.	Up to Month 60
In vivo cellular PK profile of tisagenelecleucel	qPCR and flow cytometry to measure tisagenlecleucel transgene concentration in blood, bone marrow and other matrices/tissues.	Up to Month 60
Concentration of Tocilizumab PK in tocilizumab treated subjects during CRS	Concentration of Tocilizumab	Up to Day 7 after tocilizumab infusion
Serum cytokines (IL-10, interferon gamma, IL-6, CRP and ferritin)	Concentration of soluble factors (IL-10, interferon gamma, IL-6, CRP and ferritin) will be listed and summarized by participant and time point.	Up to Month 60

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 31, 2022
• Primary Completion (Anticipated): October 31, 2022
• Study Completion (Anticipated): September 27, 2027

Study Registration Dates

• First Submitted: June 29, 2020
• First Submitted That Met QC Criteria: June 29, 2020
• First Posted (Actual): July 2, 2020

Study Record Updates

• Last Update Posted (Actual): March 2, 2022
• Last Update Submitted That Met QC Criteria: February 25, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Chinese; CTL019; Diffuse Large B-cell Lymphoma; tisagenlecleucel; relapsed/refractory; double/triple hit lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: CCTL019C2203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No