NCT05959720

Adult Acute Lymphoblastic Leukemia Treated With Pediatric Regimen in Brazil

Adult Acute Lymphoblastic Leukemia Treated With Pediatric Regimen in Brazil - a Prospective Collaborative Study

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 180 (estimated)
• Sponsor: Instituto do Cancer do Estado de São Paulo · Academic / Other
• Sex: All
• Age: 16 Years – 50 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Acute Lymphoid Leukemia
• Minimal Residual Disease
• Gene Abnormality
• Chemotherapeutic Toxicity

Interventions

Type	Name	Description
DRUG	Prednisone	60 mg/m2 D1 to D21
DRUG	Vincristin	1.5 mg/m2 D1, D8, D15 and D22
DRUG	Daunorubicin	40 mg/m2 D1, D8, D15 and D22
DRUG	Peg-asparaginase	2000 UI/m2 D12 and D26
DRUG	Intrathecal Suspension	MTX 12 mg, Dexamethasone 2 mg, Cytarabine 60 mg D1, D8, D15, D22, D29
DRUG	Cyclophosphamide	1000 mg/m2 D36 and D64
DRUG	Cytarabine	75 mg/m2 D36 to D39, D43 to D46, D50 to D53 and D57 to D60
DRUG	Mercaptopurine	30 mg/m2 D36 to D63 and D1 to D56 of consolidation
DRUG	Methotrexate	3.000 mg/m2 D8, D22, D36 and D50
DRUG	Doxorubicin	30 mg/m2 D1 and D22

Timeline

• Start date: 2023-09-05
• Primary completion: 2028-06-01
• Completion: 2030-06-01
• First posted: 2023-07-25
• Last updated: 2025-05-07

Locations

1 site across 1 country: Brazil

Regulatory

• FDA-regulated drug study