Adult Acute Lymphoblastic Leukemia Treated With Pediatric Regimen in Brazil
- Conditions
- Acute Lymphoid LeukemiaMinimal Residual DiseaseGene AbnormalityChemotherapeutic Toxicity
- Interventions
- Registration Number
- NCT05959720
- Lead Sponsor
- Instituto do Cancer do Estado de São Paulo
- Brief Summary
In this project, the investigators intend to start a prospective registry for patients with newly diagnosed Philadelphia-negative ALL from 16 years old and above in participating centers, provided that all patients will be treated with the same regimen (a pediatric regimen BFM-based incorporating peg-asparaginase). All diagnostic/follow-up (after induction and consolidation blocks) samples will be centrally biobanked at Instituto do Cancer do Estado de Sao Paulo. The main goal of this study is to examine whether the implementation of a pediatric protocol under a prospective registry can increase event-free survival (EFS) and overall survival (OS) of newly diagnosed patients in the participating centers.
- Detailed Description
Notably, pediatric regimens for adult acute lymphoblastic leukemia (ALL) have resulted in better long-term outcomes, especially in the Philadelphia-negative counterpart. These regimens are essentially based on higher cumulative doses of asparaginase and the use of less myelotoxic agents, applying allogeneic transplantation only for high-risk ALL subsets. Recent metanalysis encompassing 27 clinical trials demonstrated an improved prognosis when these regimens are adopted. In adults, incorporation of these regimens has been hampered by a perception of higher toxicity and a more complex design, especially with asparaginase. Remarkably, this drug might bring side effects not usually seen with other cancer drugs, such as thrombosis, liver, and pancreatic toxicities. In addition, the incorporation of minimal residual disease (MRD) monitoring throughout the treatment protocol in a scheduled and standardized manner is considered paramount in the contemporary ALL treatment. Treating adult patients with acute leukemia under prospective studies allows accurate data collection and positively impacts the disease prognosis, creating a cooperative scientific environment. In Brazil, few data are available on the clinical- laboratory characteristics of ALL in adults and their outcomes under a standardized treatment protocol. Few single-center reports point to a worse overall survival rate when compared to developed countries. There is great heterogeneity across the centers regarding the treatment regimens and genetic/MRD assessment. In this project, the investigators intend to start a prospective registry for patients with newly diagnosed Philadelphia-negative ALL from 16 years old and above in participating centers, provided that all patients will be treated with the same regimen (a pediatric regimen BFM-based incorporating peg-asparaginase). All diagnostic/follow-up (after induction and consolidation blocks) samples will be centrally biobanked at Instituto do Cancer do Estado de Sao Paulo. At the diagnosis, a genetic characterization encompassing conventional karyotype, fluorescent in-situ hybridization (FISH), and molecular biology in our central laboratory will be performed to classify the cases. Genomic classification will include identifying Philadelphia- like B-cell ALL cases, a recent group of cases with worse prognosis, whose incidence seems higher in Hispanics. In Brazil, there is no study addressing this incidence and, more importantly, evaluating its impact on outcomes under a standardized treatment protocol. MRD analysis will also be centralized to standardize and validate our flow cytometry panel in a homogeneous cohort. Additionally, the investigators plan to assess baseline factors predictive of survival and relapse and those related to major toxicities such as infections, liver toxicity, and thrombosis.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 180
Patients between 16 and 50 years-old with newly diagnosed ALL, negative for Philadelphia chromosome not previously treated (except for hydroxyurea, corticosteroids, or intrathecal chemotherapy) with 20% or more lymphoblasts in bone marrow or peripheral blood.
- Burkitt leukemia
- Prior myeloproliferative disease
- Philadelphia chromosome positivity through whichever methodology (RT-PCR, FISH, or conventional karyotype)
- ECOG>2 (appendix 3)
- Total bilirubin>2x upper limit of normal (ULN)
- Transaminases>5x ULN
- Creatinine>2,5 mg/dl
- Positive serology for HIV or HTLV
- Heart failure NYHA Class III or IV (appendix 4)
- Severe psychiatric disorder which prevents adequate compliance
- Prior treatment with intravenous chemotherapy
- Refusal to participate in the study
- Down syndrome
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Eligible patients Mercaptopurine All patients deemed eligible to intensive protocol of treatment are going to be included as sole group. There is no intervention or control group in this trial. Eligible patients Intrathecal Suspension All patients deemed eligible to intensive protocol of treatment are going to be included as sole group. There is no intervention or control group in this trial. Eligible patients Prednisone All patients deemed eligible to intensive protocol of treatment are going to be included as sole group. There is no intervention or control group in this trial. Eligible patients Vincristin All patients deemed eligible to intensive protocol of treatment are going to be included as sole group. There is no intervention or control group in this trial. Eligible patients Daunorubicin All patients deemed eligible to intensive protocol of treatment are going to be included as sole group. There is no intervention or control group in this trial. Eligible patients Peg-asparaginase All patients deemed eligible to intensive protocol of treatment are going to be included as sole group. There is no intervention or control group in this trial. Eligible patients Cyclophosphamide All patients deemed eligible to intensive protocol of treatment are going to be included as sole group. There is no intervention or control group in this trial. Eligible patients Cytarabine All patients deemed eligible to intensive protocol of treatment are going to be included as sole group. There is no intervention or control group in this trial. Eligible patients Doxorubicin All patients deemed eligible to intensive protocol of treatment are going to be included as sole group. There is no intervention or control group in this trial. Eligible patients Methotrexate All patients deemed eligible to intensive protocol of treatment are going to be included as sole group. There is no intervention or control group in this trial.
- Primary Outcome Measures
Name Time Method Overall survival (OS) 4 years cumulative proportion of patients alive (considering the time between the date of diagnosis and death or last follow-up)
- Secondary Outcome Measures
Name Time Method Cumulative incidence of relapse 4 years rate of disease relapse after CR calculated considering death as a competing event.
Complete response rate 60 days proportion of patients with bone marrow aspirate with less than 5% blasts and evidence of normal hematopoiesis; CSF without blasts and recovery of peripheral blood (neutrophils≥ 1,000/μL and platelets≥100,000/μL), without the need for transfusion
Event-free survival (EFS) 4 years time between enrollment in the study and the occurrence of any event: refractoriness after the first two cycles of induction, death or relapse.
Early death rate 60 days proportion of patients who died before the first bone marrow evaluation of response (after induction I)
HSCT rate 2 years proportion of patients eligible for the protocol who were able to perform the procedure in their first CR
Trial Locations
- Locations (1)
Instituto do Cancer do Estado de Sao Paulo
🇧🇷São Paulo, SP, Brazil