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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Withdrawn
• CT.gov ID: NCT04456023
• Collaborator: (none)
• Enrollment: 0
• Arm: 1
• Anticipated Duration (Months): 67.8

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B-Cell Lymphoma (DLBCL)	Biological: Tisagenlecleucel	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 0 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Anticipated Study Start Date: Jan 31, 2022
• Anticipated Primary Completion Date: Oct 31, 2022
• Anticipated Study Completion Date: Sep 27, 2027

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR) [From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months]

   Complete Response (CR) and Partial Response (PR) according to the Lugano classification as determined by the Investigator.

Secondary Outcome Measures

1. Duration of Response (DOR) [From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months]

   Time from CR or PR, whichever occurs first, to relapse or death due to DLBCL.

2. Time to response (TTR) [From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months]

   Time from tisagenlecleucel infusion to CR or PR, whichever occurs first.

3. Progression-Free Survival (PFS) [From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months]

   Time from tisagenlecleucel infusion to the first documented disease progression or death due to any cause.

4. Event free survival (EFS) [From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months]

   Time from tisagenlecleucel infusion to the first documented disease progression or relapse, new treatment for lymphoma or death due to any cause.

5. Overall Survival (OS) [From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months]

   Time from tisagenlecleucel infusion to death due to any cause.

6. Number of Participants with On-Treatments Adverse Events, Serious Adverse Events, and Deaths [From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months]

   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.

7. Tisagenlecleucel immunogenicity (humoral) [Up to Month 60]

   The humoral immunogenicity assay will be evaluated to measure the antibody titers specific to the tisagenlecleucel molecule prior to and following infusion.

8. Tisagenlecleucel immunogenicity (cellular) [Up to Month 60]

   The cellular immunogenicity assay will be evaluated to assess the presence of T lymphocytes activated by the tisagenlecleucel protein.

9. In vivo cellular PK profile of tisagenelecleucel [Up to Month 60]

   qPCR and flow cytometry to measure tisagenlecleucel transgene concentration in blood, bone marrow and other matrices/tissues.

10. Concentration of Tocilizumab PK in tocilizumab treated subjects during CRS [Up to Day 7 after tocilizumab infusion]

    Concentration of Tocilizumab

11. Serum cytokines (IL-10, interferon gamma, IL-6, CRP and ferritin) [Up to Month 60]

    Concentration of soluble factors (IL-10, interferon gamma, IL-6, CRP and ferritin) will be listed and summarized by participant and time point.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. Adequate organ function

2. 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04456023
• Other Study ID Numbers: CCTL019C2203
• First Posted: Jul 2, 2020
• Last Update Posted: Mar 2, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Diffuse Large B-cell Lymphoma; double/triple hit lymphoma; relapsed/refractory; tisagenlecleucel; CTL019; Chinese
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse

Study Results

No Results Posted as of Mar 2, 2022