Effectiveness and Safety Study of Tisagenlecleucel in Brazilian Patients With Acute Lymphoblastic Leukemia or Diffuse Large B-cell Lymphoma

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05541341
Collaborator
(none)
200
180

Study Details

Study Description

Brief Summary

This post-authorization safety investigation will be a multicenter, non-interventional, prospective cohort study.

Condition or Disease Intervention/Treatment Phase
  • 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, with at least 100 lymphoma patients who received tisagenlecleucel for the treatment of relapsed/refractory Diffuse Large B-cell Lymphoma (DLBCL).

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 until just prior to infusion with tisagenlecleucel.

  • "Follow-up Post infusion" information will comprise any information from the infusion of tisagenlecleucel onwards.

Study Design

Study Type:
Observational
Anticipated Enrollment :
200 participants
Observational Model:
Cohort
Time Perspective:
Other
Official Title:
Effectiveness and Safety of Tisagenlecleucel Therapy in Brazilian Patients With Acute Lymphoblastic Leukemia or Diffuse Large B-cell Lymphoma: a 15-year Prospective Registry Study on Two Cohorts
Anticipated Study Start Date :
Dec 16, 2022
Anticipated Primary Completion Date :
Dec 16, 2037
Anticipated Study Completion Date :
Dec 16, 2037

Arms and Interventions

Arm 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 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 are eligible to enroll into this study.

Outcome Measures

Primary Outcome Measures

  1. Overall response rate (ORR) [Up to 15 years]

    The overall response rate will be defined as the total proportion of participants exhibiting either complete or partial responses. For ALL participants, the best disease response will be defined as a Complete Remission (CR) or a complete remission with incomplete blood count recovery (CRi) in accordance with National Comprehensive Cancer Network (NCCN) guidelines and previous guidelines (Appelbaum et al 2007)(Cheson et al 2003). For lymphomas, the best disease response will be defined as a CR (Complete Response) or PR (Partial Response) in accordance with the Cheson response criteria (Cheson et al 2007) and the Lugano classification (Cheson et al 2016).

  2. MRD negative overall response rate [Up to 15 years]

    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

  3. Duration of overall response (DOR) [Up to 15 years]

    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.

  4. Relapse-free survival (RFS) [Up to 15 years]

    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.

  5. Event-free survival (EFS) for ALL patients [Up to 15 years]

    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.

  6. Progression free survival (PFS) for DLBCL patients [Up to 15 years]

    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.

  7. Overall survival (OS) [Up to 15 years]

    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.

  8. Number of ALL patients with hematologic recovery [Up to 15 years]

    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).

Secondary Outcome Measures

  1. The type and frequency of SAEs and AE of special interest [Up to 15 years]

    The type and frequency of SAEs and AE of special interest (including secondary malignancies) will be collected

  2. Incidence and severity of CRS and ICANS among HTLV 1 and 2 positive versus HTLV 1 and 2 negative patients [Up to 15 years]

    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

  3. Pregnancy rates [Up to 15 years]

    Pregnancy rates will be collected

  4. Number of patients with confirmed secondary malignancies diagnosis [Up to 15 years]

    Number of patients with confirmed secondary malignancies diagnosis will be collected

Eligibility Criteria

Criteria

Ages Eligible for Study:
N/A to 100 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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 Acute Lymphoblastic Leukemia (ALL) participants:
  1. Patients of any gender aged 0-17 years (named as pediatric) with relapsed/ refractory B-cell ALL diagnosis that received tisagenlecleucel infusion, OR

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

For Diffuse Large B-cell Lymphoma (DBLCL) participants:
  1. 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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT05541341
Other Study ID Numbers:
  • CCTL019BBR02
First Posted:
Sep 15, 2022
Last Update Posted:
Sep 15, 2022
Last Verified:
Sep 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:

Study Results

No Results Posted as of Sep 15, 2022