Effectiveness and Safety of Tisagenlecleucel Therapy in Brazilian Patients With B-lymphocyte Malignancies: a 15-year Prospective Registry Study on Three Cohorts.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- MRD negative overall response rate
研究概览
简要总结
This will be a multicenter, national, non-interventional, prospective cohort study
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- 0 Years 至 100 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients eligible for inclusion in this study must meet the following criteria:
- •Patients who receive tisagenlecleucel infusion in the commercial setting or out-of-specification (OOS) use, AND
- •Signed informed consent must be obtained prior to participation in study, AND
- •For ALL participants:
- •Patients of any gender aged 0-17 years (named as pediatric) with relapsed/ refractory B-cell ALL diagnosis that received tisagenlecleucel infusion, OR
- •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:
- •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.
排除标准
- •Patients who did not consent to data collection.
- •Patients who received tisagenlecleucel infusion as part of any interventional clinical trial.
结局指标
主要结局
MRD negative overall response rate
时间窗: 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 with 95% CI.
Relapse-free survival (RFS)
时间窗: 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.
Progression free survival (PFS) for DLBCL patients
时间窗: 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.
Duration of overall response (DOR)
时间窗: 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.
Event-free survival (EFS) for ALL patients
时间窗: 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.
Overall survival (OS)
时间窗: 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.
Number of ALL patients with hematologic recovery
时间窗: 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).
Overall response rate (ORR)
时间窗: Up to 15 years
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).
次要结局
- The type and frequency of SAEs and AE of special interest(Up to 15 years)
- Pregnancy rates(Up to 15 years)
- Incidence and severity of CRS and ICANS among HTLV 1 and 2 positive versus HTLV 1 and 2 negative patients(Up to 15 years)
- Number of patients with confirmed secondary malignancies diagnosis(Up to 15 years)