Adult Acute Lymphoblastic Leukemia Treated With Pediatric Regimen in Brazil (BRALLA)

Instituto do Cancer do Estado de São Paulo

Status

Enrolling

Conditions

Acute Lymphoid Leukemia

Chemotherapeutic Toxicity

Gene Abnormality

Minimal Residual Disease

Treatments

Drug: Intrathecal Suspension

Drug: Doxorubicin

Drug: Vincristin

Drug: Prednisone

Drug: Peg-asparaginase

Drug: Cytarabine

Drug: Mercaptopurine

Drug: Methotrexate

Drug: Cyclophosphamide

Drug: Daunorubicin

Study type

Observational

Funder types

Other

Industry

Identifiers

NCT05959720

3011/22

Details and patient eligibility

About

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.

Full 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.

Enrollment

180 estimated patients

Sex

All

Ages

16 to 50 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria: 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.

Exclusion Criteria:

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

Trial design

180 participants in 1 patient group

Eligible patients

Description:

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.

Treatment: