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

Primary Purpose

Diffuse Large B-Cell Lymphoma (DLBCL)

Status

Withdrawn

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Tisagenlecleucel

About this trial

This is an interventional treatment trial for Diffuse Large B-Cell Lymphoma (DLBCL) focused on measuring Diffuse Large B-cell Lymphoma, double/triple hit lymphoma, relapsed/refractory, tisagenlecleucel, CTL019, Chinese

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Signed informed consent must be obtained prior to participation in the study
Patients must be ≥18 years of age at the time of ICF signature
Histologically confirmed DLBCL at last relapse (including DLBCL transformed from follicular lymphoma and double-triple hit lymphoma)
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
ECOG performance status that is either 0 or 1 at screening
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
Adequate organ function
Must have a leukapheresis material of non-mobilized cells available for manufacturing

Exclusion Criteria:

Prior treatment with anti-CD19 therapy, adoptive T cell therapy, or any prior gene therapy product
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.
Eligible for and consenting to autologous HSCT
Prior allogeneic SCT
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
Active neurological autoimmune or inflammatory disorders (e.g. Guillain-Barre syndrome)
Investigational medicinal product within the last 30 days or five half-lives (whichever is longer) prior to screening

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tisagenlecleucel

Arm Description

All patients eligible for treatment with tisagenlecleucel will receive a single dose of tisagenlecleucel.

Outcomes

Primary Outcome Measures

Overall Response Rate (ORR)

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

Secondary Outcome Measures

Duration of Response (DOR)

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

Time to response (TTR)

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

Progression-Free Survival (PFS)

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

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.

Overall Survival (OS)

Time from tisagenlecleucel infusion to death due to any cause.

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.

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.

Tisagenlecleucel immunogenicity (cellular)

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

In vivo cellular PK profile of tisagenelecleucel

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

Concentration of Tocilizumab PK in tocilizumab treated subjects during CRS

Concentration of Tocilizumab

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.

Full Information

NCT ID

NCT04456023

First Posted

June 29, 2020

Last Updated

February 25, 2022

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT04456023

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

February 2022

Overall Recruitment Status

Withdrawn

Why Stopped

This study was cancelled before enrolling any patients for business related reasons.

Study Start Date

January 31, 2022 (Anticipated)

Primary Completion Date

October 31, 2022 (Anticipated)

Study Completion Date

September 27, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diffuse Large B-Cell Lymphoma (DLBCL)

Keywords

Diffuse Large B-cell Lymphoma, double/triple hit lymphoma, relapsed/refractory, tisagenlecleucel, CTL019, Chinese

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Tisagenlecleucel

Arm Type

Experimental

Arm Description

All patients eligible for treatment with tisagenlecleucel will receive a single dose of tisagenlecleucel.

Intervention Type

Biological

Intervention Name(s)

Tisagenlecleucel

Other Intervention Name(s)

CTL019

Intervention Description

A single intravenous (i.v.) infusion of 0.6 - 6.0×10^8 CAR positive viable T cells.

Primary Outcome Measure Information:

Title

Overall Response Rate (ORR)

Description

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

Time Frame

From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months

Secondary Outcome Measure Information:

Title

Duration of Response (DOR)

Description

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

Time Frame

From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months

Title

Time to response (TTR)

Description

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

Time Frame

From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months

Title

Progression-Free Survival (PFS)

Description

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

Time Frame

From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months

Title

Event free survival (EFS)

Description

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

Time Frame

From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months

Title

Overall Survival (OS)

Description

Time from tisagenlecleucel infusion to death due to any cause.

Time Frame

From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months

Title

Number of Participants with On-Treatments Adverse Events, Serious Adverse Events, and Deaths

Description

Time Frame

From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months

Title

Tisagenlecleucel immunogenicity (humoral)

Description

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

Time Frame

Up to Month 60

Title

Tisagenlecleucel immunogenicity (cellular)

Description

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

Time Frame

Up to Month 60

Title

In vivo cellular PK profile of tisagenelecleucel

Description

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

Time Frame

Up to Month 60

Title

Concentration of Tocilizumab PK in tocilizumab treated subjects during CRS

Description

Concentration of Tocilizumab

Time Frame

Up to Day 7 after tocilizumab infusion

Title

Serum cytokines (IL-10, interferon gamma, IL-6, CRP and ferritin)

Description

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

Time Frame

Up to Month 60

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study Patients must be ≥18 years of age at the time of ICF signature Histologically confirmed DLBCL at last relapse (including DLBCL transformed from follicular lymphoma and double-triple hit lymphoma) 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 ECOG performance status that is either 0 or 1 at screening 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 Adequate organ function Must have a leukapheresis material of non-mobilized cells available for manufacturing Exclusion Criteria: Prior treatment with anti-CD19 therapy, adoptive T cell therapy, or any prior gene therapy product 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. Eligible for and consenting to autologous HSCT Prior allogeneic SCT 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 Active neurological autoimmune or inflammatory disorders (e.g. Guillain-Barre syndrome) Investigational medicinal product within the last 30 days or five half-lives (whichever is longer) prior to screening

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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

IPD Sharing URL

https://www.clinicalstudydatarequest.com

Citations:

PubMed Identifier

34515338

Citation

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.

Results Reference

derived

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

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