Clinical trial NCT04456023: 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
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Diffuse Large B-Cell Lymphoma (DLBCL)
Keywords: Diffuse Large B-cell Lymphoma
double/triple hit lymphoma
relapsed/refractory
tisagenlecleucel
CTL019
Chinese
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-07-02
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
measure: Time to response (TTR)
timeFrame: From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
measure: Progression-Free Survival (PFS)
timeFrame: From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
measure: Event free survival (EFS)
timeFrame: From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
measure: Overall Survival (OS)
timeFrame: From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
measure: Number of Participants with On-Treatments Adverse Events, Serious Adverse Events, and Deaths
timeFrame: From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
measure: Tisagenlecleucel immunogenicity (humoral)
timeFrame: Up to Month 60
measure: Tisagenlecleucel immunogenicity (cellular)
timeFrame: Up to Month 60
measure: In vivo cellular PK profile of tisagenelecleucel
timeFrame: Up to Month 60
measure: Concentration of Tocilizumab PK in tocilizumab treated subjects during CRS
timeFrame: Up to Day 7 after tocilizumab infusion
measure: Serum cytokines (IL-10, interferon gamma, IL-6, CRP and ferritin)
timeFrame: Up to Month 60
Other outcomes:
Locations:
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
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.