Adult Acute Lymphoblastic Leukemia Treated With Pediatric Regimen in Brazil

NCT ID: NCT05959720

Last Updated: 2025-05-07

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 180 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-09-05
• Study Completion Date: 2030-06-30

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.

Conditions

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Eligible patients

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.

Prednisone

Intervention Type: DRUG

60 mg/m2 D1 to D21

Vincristin

Intervention Type: DRUG

1.5 mg/m2 D1, D8, D15 and D22

Daunorubicin

Intervention Type: DRUG

40 mg/m2 D1, D8, D15 and D22

Peg-asparaginase

Intervention Type: DRUG

2000 UI/m2 D12 and D26

Intrathecal Suspension

Intervention Type: DRUG

MTX 12 mg, Dexamethasone 2 mg, Cytarabine 60 mg D1, D8, D15, D22, D29

Cyclophosphamide

Intervention Type: DRUG

1000 mg/m2 D36 and D64

Cytarabine

Intervention Type: DRUG

75 mg/m2 D36 to D39, D43 to D46, D50 to D53 and D57 to D60

Mercaptopurine

Intervention Type: DRUG

30 mg/m2 D36 to D63 and D1 to D56 of consolidation

Methotrexate

Intervention Type: DRUG

3.000 mg/m2 D8, D22, D36 and D50

Doxorubicin

Intervention Type: DRUG

30 mg/m2 D1 and D22

Interventions

Prednisone

60 mg/m2 D1 to D21

Intervention Type: DRUG

Vincristin

1.5 mg/m2 D1, D8, D15 and D22

Intervention Type: DRUG

Daunorubicin

40 mg/m2 D1, D8, D15 and D22

Intervention Type: DRUG

Peg-asparaginase

2000 UI/m2 D12 and D26

Intervention Type: DRUG

Intrathecal Suspension

MTX 12 mg, Dexamethasone 2 mg, Cytarabine 60 mg D1, D8, D15, D22, D29

Intervention Type: DRUG

Cyclophosphamide

1000 mg/m2 D36 and D64

Intervention Type: DRUG

Cytarabine

75 mg/m2 D36 to D39, D43 to D46, D50 to D53 and D57 to D60

Intervention Type: DRUG

Mercaptopurine

30 mg/m2 D36 to D63 and D1 to D56 of consolidation

Intervention Type: DRUG

Methotrexate

3.000 mg/m2 D8, D22, D36 and D50

Intervention Type: DRUG

Doxorubicin

30 mg/m2 D1 and D22

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Servier

INDUSTRY

Sponsor Role: collaborator

Instituto do Cancer do Estado de São Paulo

OTHER

Sponsor Role: lead

Responsible Party

Wellington Fernandes

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Wellington F Silva, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Instituto do Cancer do Estado de São Paulo

Eduardo M Rego, MD PhD

Role: STUDY_CHAIR

Instituto do Cancer do Estado de São Paulo

Locations

Instituto do Cancer do Estado de Sao Paulo

São Paulo, São Paulo, Brazil

Site Status: RECRUITING

Countries

Brazil

Central Contacts

Graziela Silva

Role: CONTACT

graziela.sasilva@hc.fm.usp.br

551138934677

Bruna Moraes, MSc

Role: CONTACT

pesquisa.hematologia@hc.fm.usp.br

551126628112

Facility Contacts

Wellington F Silva, MD PhD

Role: primary

wellington.fernandes@hc.fm.usp.br

551138944677

References

Silva WF, Amano MT, Perruso LL, Cordeiro MG, Kishimoto RK, de Medeiros Leal A, Nardinelli L, Bendit I, Velloso ED, Rego EM, Rocha V. Adult acute lymphoblastic leukemia in a resource-constrained setting: outcomes after expansion of genetic evaluation. Hematology. 2022 Dec;27(1):396-403. doi: 10.1080/16078454.2022.2052602.

Reference Type: BACKGROUND

PMID: 35344469 (View on PubMed)

Other Identifiers

3011/22

Identifier Type: -

Identifier Source: org_study_id