Effectiveness and Safety of Tisagenlecleucel Therapy in Brazilian Patients With B-lymphocyte Malignancies

Effectiveness and Safety of Tisagenlecleucel Therapy in Brazilian Patients With B-lymphocyte Malignancies: a 15-year Prospective Registry Study on Three Cohorts.

This will be a multicenter, national, non-interventional, prospective cohort study

Study Overview

• Status: Recruiting
• Conditions: Follicular Lymphoma; Acute Lymphoblastic Leukemia; Diffuse Large B-cell Lymphoma
• Intervention / Treatment: Other: tisagenlecleucel

Detailed Description

Eligible participants will be pediatric (<18 years) and adult patients (aged 18 years or older) with B-cell malignancies who have received tisagenlecleucel through the commercial setting or out-of-specification (OOS) use in Brazil. We will collect data prospectively and complement missing information with retrospective data collection, when necessary. It is anticipated that approximately 200 patients will be enrolled in the cohort over 5 years divided among the study indications.

Since this is a non-interventional study, no administration of study drug or application of questionnaires will be mandated by this protocol. The study will consist of a "Pre-infusion" and a "Post infusion follow-up period" for up to 15 years post tisagenlecleucel infusion. All patients will be followed until death or last scheduled visit, whichever comes first.

For the study, "pre-infusion" and "follow-up post infusion" phases are defined as:

• "Pre-infusion" will consist of the patient's information from the time of diagnosis untiljust prior to infusion with tisagenlecleucel.
• "Follow-up Post infusion" information will comprise any information from the infusionof tisagenlecleucel onwards.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: +41613241111; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals

Study Locations

• Brazil
  • Sao Paulo, Brazil, 01409-902
    • Recruiting
    • Novartis Investigative Site
  • Sao Paulo, Brazil, 01509-010
    • Recruiting
    • Novartis Investigative Site
  • BA
    • Salvador, BA, Brazil, 41253-190
      • Recruiting
      • Novartis Investigative Site
  • Belo Horizonte
    • Minas Gerais, Belo Horizonte, Brazil, 34006-059
      • Recruiting
      • Novartis Investigative Site
  • PR
    • Curitiba, PR, Brazil, 81520-060
      • Recruiting
      • Novartis Investigative Site
  • SP
    • Sao Paulo, SP, Brazil, 01323-900
      • Recruiting
      • Novartis Investigative Site
    • Sao Paulo, SP, Brazil, 04544-000
      • Recruiting
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 100 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population will include pediatric/ adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia aged 0-25 years and adult patients aged ≥ 18 years with relapsed/refractory Diffuse Large B-cell Lymphoma and relapsed/refractory follicular lymphoma, who received tisagenlecleucel infusion in the commercial setting or out-of-specification.

Description

Inclusion Criteria:

Patients eligible for inclusion in this study must meet the following criteria:

1. Patients who receive tisagenlecleucel infusion in the commercial setting or out-of-specification (OOS) use, AND

2. Signed informed consent must be obtained prior to participation in study, AND

   For ALL participants:

3. Patients of any gender aged 0-17 years (named as pediatric) with relapsed/ refractory B-cell ALL diagnosis that received tisagenlecleucel infusion, OR

4. Patients of any gender, aged 18-25 years (named as adults) - with relapsed/ refractory B-cell ALL diagnosis that received tisagenlecleucel infusion, OR

   For DBLCL and FL participants:

5. Patients of any gender aged 18 years or older, who have been diagnosed with relapsed/ refractory Diffuse Large B-cell Lymphoma and received tisagenlecleucel infusion.

Exclusion Criteria:

1. Patients who did not consent to data collection.
2. Patients who received tisagenlecleucel infusion as part of any interventional clinical trial.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Acute Lymphoblastic Leukemia (ALL); Children/young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia who received tisagenlecleucel infusion	Other: tisagenlecleucel; Prospective observational study. There is no treatment allocation. Patients prescribed with tisagenlecleucel in the commercial setting or out-of-specification (OOS) are eligible to enroll into this study
Diffuse Large B-cell Lymphoma (DLBCL); Adult patients with relapsed/refractory Diffuse Large B-cell Lymphoma who received tisagenlecleucel infusion	Other: tisagenlecleucel; Prospective observational study. There is no treatment allocation. Patients prescribed with tisagenlecleucel in the commercial setting or out-of-specification (OOS) are eligible to enroll into this study
Follicular Lymphoma (FL); Patients of any gender aged 18 year or older, with relapsed/refractory Follicular Lymphoma who received tisagenlecleucel infusion.	Other: tisagenlecleucel; Prospective observational study. There is no treatment allocation. Patients prescribed with tisagenlecleucel in the commercial setting or out-of-specification (OOS) are eligible to enroll into this study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of overall response (DOR)	Duration of overall response (DOR) applies only to patients whose best overall disease response was either: CR or PR for patients with lymphomas, or; CR or a CRi for patients with ALL. DOR will be defined as the time from the date of first documented disease response (Complete Response (CR) or PR for patients with lymphomas, and Complete Remission (CR) or CRi for patients with ALL), whichever occurs first, to the date of first documented progression or first documented relapse according to indication, or to the date of death due to the underlying disease. In case a patient does not have progression/relapse or death due to underlying disease (defined as the event for this outcome) prior to data cut-off, DOR will be censored at the date of the last assessment on or prior to the earliest censoring event.	Up to 15 years
Relapse-free survival (RFS)	RFS is measured by the time from date of first documented disease response as CR or CRi to relapse or death due to any cause in ALL patients. In case a patient does not have relapse or death due to any cause prior to data cutoff, RFS will be censored at the date of the last adequate assessment on or prior to the earliest censoring event.	Up to 15 years
Event-free survival (EFS) for ALL patients	EFS is the time from date of first tisagenlecleucel infusion to treatment failure, relapse or death from any cause, whichever occurred first, for B-cell ALL patients.	Up to 15 years
Progression free survival (PFS) for DLBCL patients	PFS is defined as the time from the date of first infusion to the date of event defined as the first documented progression of lymphoma or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of the last adequate assessment. In case a patient does not have progression or death prior to data cutoff, PFS will be censored at the date of the last adequate assessment on or prior to the earliest censoring event.	Up to 15 years
Overall survival (OS)	Overall survival is the time from date of first tisagenlecleucel infusion to the date of death due to any reason, In case a patient is alive at the date of last contact on or before data cutoff, OS is censored at the date of last contact.	Up to 15 years
Number of ALL patients with hematologic recovery	Dates of hematological recovery (i.e., dates of Absolute Neutrophil Count (ANC) and platelet recovery) will be collected. ANC recovery is defined as an ANC of ≥ 0.5 × 109/L (500/mm^3) for 3 consecutive laboratory values obtained on different days. Date of ANC recovery is the date of the first of 3 consecutive laboratory values where the ANC is ≥ 0.5 × 109/L (CIBMTR). The first date of the 3 consecutive laboratory values obtained on different days where the platelet count was ≥ 20 × 109/L should be recorded. It should be ensured that no platelet transfusions were administered for 7 days immediately preceding this date (CIBMTR).	Up to 15 years
Overall response rate (ORR)	The overall response rate will be defined as the total proportion of participants exhibiting either the best overall response (BOR) of complete or partial responses and the proportion of patient with BOR of CR/PR or CR/CRi for ALL patients will be reported along with its 95% CI. For ALL participants, the BOR will be defined as a CR or a CRi in accordance with National Comprehensive Cancer Network (NCCN) guidelines and previous guidelines (Appelbaum et al 2007)(Cheson et al 2003). For lymphomas, the BOR will be defined as a CR or PR in accordance with the Cheson response criteria (Cheson et al 2007) and the Lugano classification (Cheson et al 2016).	Up to 15 years
MRD negative overall response rate	The percentage of B-cell ALL patients who achieve a Best Overall Response (BOR) of CR or CRi with a Minimal residual disease (MRD) negative bone marrow will be provided with 95% CI.	Up to 15 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The type and frequency of SAEs and AE of special interest	The type and frequency of SAEs and AE of special interest (including secondary malignancies) will be collected	Up to 15 years
Incidence and severity of CRS and ICANS among HTLV 1 and 2 positive versus HTLV 1 and 2 negative patients	Incidence and severity of Cytokine release syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) among Human T-cell Lymphotropic Virus (HTLV) 1 and 2 positive versus HTLV 1 and 2 negative patients. For CRS AE the protocol will follow the American Society of Transplant and Cellular Therapy (ASTCT) CRS Consensus Grading. For ICANS AE the protocol will follow ASTCT consensus as well. Which establishes the Immune effector Cell-associated Encephalopathy (ICE Score) for adults/ adolescents and Cornell Assessment of Pediatric Delirium (CAPD) for pediatric patients under 12 years	Up to 15 years
Pregnancy rates	Pregnancy rates will be collected	Up to 15 years
Number of patients with confirmed secondary malignancies diagnosis	Number of patients with confirmed secondary malignancies diagnosis will be collected	Up to 15 years

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2023
• Primary Completion (Estimated): November 23, 2043
• Study Completion (Estimated): November 23, 2043

Study Registration Dates

• First Submitted: September 13, 2022
• First Submitted That Met QC Criteria: September 13, 2022
• First Posted (Actual): September 15, 2022

Study Record Updates

• Last Update Posted (Actual): June 6, 2025
• Last Update Submitted That Met QC Criteria: June 5, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: DLBCL; ALL; Follicular Lymphoma; NIS; Acute Lymphoblastic Leukemia; Diffuse Large B-cell Lymphoma; Brazil; Tisagenlecleucel
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Leukemia; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Follicular; Antineoplastic Agents, Immunological; Antineoplastic Agents; Tisagenlecleucel
• Other Study ID Numbers: CCTL019BBR02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO