Clinical Trials /

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

NCT04456023

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Double-Hit Lymphoma
  • Transformed Non-Hodgkin Lymphoma
  • Triple-Hit Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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)

Clinical Trial IDs

  • ORG STUDY ID: CCTL019C2203
  • NCT ID: NCT04456023

Conditions

  • Diffuse Large B-Cell Lymphoma (DLBCL)

Interventions

DrugSynonymsArms
TisagenlecleucelCTL019Tisagenlecleucel

Purpose

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).
    

Trial Arms

NameTypeDescriptionInterventions
TisagenlecleucelExperimentalAll patients eligible for treatment with tisagenlecleucel will receive a single dose of tisagenlecleucel.
  • Tisagenlecleucel

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

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

Last Updated

April 21, 2021