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:Overall Response Rate (ORR) is defined as the percentage of participants with best overall response of Complete Response (CR) or Partial Response (PR), where the best overall disease response is defined as the best disease response recorded from tisagenlecleucel infusion until progressive disease or start of new anticancer therapy, whichever comes first. The overall response assessment is based on the amended Lugano classification assessed 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:Duration of response (DOR) applies only to subjects whose best overall disease response was CR or PR. It is defined as the time from the date of first documented disease response (CR or PR) to the date of first documented progression or death due to Diffuse Large B Cell Lymphoma (DLBCL). If a subject has not had an event, duration of overall response is censored at the date of the last adequate assessment.
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 to response (TTR) is defined as the time from the date of tisagenlecleucel infusion to the date of first documented disease response (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:Progression-Free Survival (PFS) is defined as the time from tisagenlecleucel infusion to the first documented disease progression or death due to any cause. If a subject has not had an event, progression-free survival is censored at the date of the last adequate assessment.
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:Event free survival (EFS) is defined as the time from tisagenlecleucel infusion to the first documented disease progression or relapse, new treatment for lymphoma (excluding hematopoietic stem cell transplantation (HSCT)) 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:Overall survival (OS) is defined as the time from tisagenlecleucel infusion to death due to any cause. If a death has not been observed by the date of analysis cutoff, OS will be censored at the date of last contact.
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 Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC) to demonstrate that single intravenous (i.v.) infusion of tisagenlecleucel is safe through the monitoring of relevant clinical and laboratory safety parameters.
Measure:Tisagenlecleucel immunogenicity (humoral)
Time Frame:Week -12 to Day -1 (Enrollment/Bridging chemotherapy), Day 28, Months 3, 6 and 12
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. Data will be further fractionated to determine proportion of subjects who make transient versus sustained antibody responses.
Measure:Tisagenlecleucel immunogenicity (cellular)
Time Frame:Week -12 to Day -1 (Enrollment/Bridging chemotherapy), Day 28, Months 3, 6 and 12
Safety Issue:
Description:The cellular immunogenicity assay will be evaluated to assess the presence of T lymphocytes activated by the tisagenlecleucel protein.
Measure:Pharmacokinetic of Tisagenlecleucel: Area Under the Curve from time zero to day 28 (AUC0-28d) and/or DAY 84 (AUC0-84d)
Time Frame:Week -12 to Day -1 (Enrollment/Bridging chemotherapy), Days 4, 7, 11, 14 and 28, Months 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54 and 60
Safety Issue:
Description:Area Under the Curve from time zero to day 28 (AUC0-28d) and/or DAY 84 (AUC0-84d) will be calculated from plasma concentration-time data using non-compartmental methods.
Measure:Pharmacokinetic of Tisagenlecleucel: Maximum Observed Plasma Concentration (Cmax)
Time Frame:Week -12 to Day -1 (Enrollment/Bridging chemotherapy), Days 4, 7, 11, 14 and 28, Months 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54 and 60
Safety Issue:
Description:Cmax is the observed maximum plasma concentration following drug administration. PK parameters are calculated from plasma concentration-time data using non-compartmental methods.
Measure:Pharmacokinetic of Tisagenlecleucel: Time to reach the maximum concentration after drug administration (Tmax)
Time Frame:Week -12 to Day -1 (Enrollment/Bridging chemotherapy), Days 4, 7, 11, 14 and 28, Months 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54 and 60
Safety Issue:
Description:Tmax is the time to reach maximum plasma concentration after single dose administration. PK parameters are calculated from plasma concentration-time data using non-compartmental methods.
Measure:Pharmacokinetic of Tisagenlecleucel: Terminal elimination half-life (T^1/2)
Time Frame:Week -12 to Day -1 (Enrollment/Bridging chemotherapy), Days 4, 7, 11, 14 and 28, Months 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54 and 60
Safety Issue:
Description:T^1/2 is the elimination half-life associated with the terminal slope of a semi logarithmic concentration-time curve. PK parameters are calculated from plasma concentration-time data using non-compartmental methods.
Measure:Pharmacokinetic of Tisagenlecleucel: last observed quantifiable concentration in peripheral blood (Clast)
Time Frame:Week -12 to Day -1 (Enrollment/Bridging chemotherapy), Days 4, 7, 11, 14 and 28, Months 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54 and 60
Safety Issue:
Description:Clast is the last observed quantifiable concentration in peripheral blood. PK parameters are calculated from plasma concentration-time data using non-compartmental methods.
Measure:Pharmacokinetic of Tisagenlecleucel: time of last observed quantifiable concentration in peripheral blood (Tlast)
Time Frame:Week -12 to Day -1 (Enrollment/Bridging chemotherapy), Days 4, 7, 11, 14 and 28, Months 3, 6, 9, 12, 18, 24, 30, 36, 40, 48, 54 and 60
Safety Issue:
Description:Tlast is the time of last observed quantifiable concentration in peripheral blood. PK parameters are calculated from plasma concentration-time data using non-compartmental methods.
Measure:Concentration of Tocilizumab PK in tocilizumab treated subjects during CRS
Time Frame:up to Day 7 after tocilizumab infusion
Safety Issue:
Description:The concentration of Tocilizumab PK will be characterized by CRS grade and the impact of tocilizumab administration on cellular kinetics will be investigated.
Measure:Serum Cytokine Levels
Time Frame:From first dosing (single administration, Day 1) up to Month 3
Safety Issue:
Description:The concentrations of soluble factors in blood and its correlation with CRS grade, neurologic toxicity and other clinical response (e.g., CR rate, MRD negativity rate, ORR, etc.) will be evaluated.

Details

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

Trial Keywords

  • B-cell lymphoma
  • lymphoma
  • b-cells
  • blood cancer
  • lymph nodes
  • non-Hodgkin
  • relapsed/refractory
  • tisagenlecleucel
  • CTL019
  • Chinese

Last Updated

June 29, 2020