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RecruitingNCT05959720BRALLAUpdated May 7, 2025

Adult Acute Lymphoblastic Leukemia Treated With Pediatric Regimen in Brazil

An observational study in Acute Lymphoid Leukemia, Minimal Residual Disease and Gene Abnormality, sponsored by Instituto do Cancer do Estado de São Paulo. Recruiting at 1 site in Brazil. Open to participants aged 16 Years to 50 Years. Per ClinicalTrials.gov, last updated 2025-05-07.

Sponsored by Instituto do Cancer do Estado de São Paulo · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
180
Ages
16 Years to 50 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Acute Lymphoid Leukemia
  • Minimal Residual Disease
  • Gene Abnormality
  • Chemotherapeutic Toxicity
03

Who can participate

Ages eligible
16 Years to 50 Years
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

All patients from 16 years and above newly diagnosed with Philadelphia-negative ALL and after the signature of informed consent form (ICF). Patients between 16 and 17 years-old will sign a child assent along with a parental consent form. ICF application might be performed even under ALL suspicion only, given the need for sample collection before any therapy, ideally.

Eligibility 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
04

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
180 participants (estimated)
Target follow-up
2 Years
Patient registry
Yes
Biospecimen retention
Samples with dna

Groups and cohorts

  • 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.

    Drug: Prednisone · Drug: Vincristin · Drug: Daunorubicin · Drug: Peg-asparaginase · Drug: Intrathecal Suspension · Drug: Cyclophosphamide · Drug: Cytarabine · Drug: Mercaptopurine · Drug: Methotrexate · Drug: Doxorubicin

Interventions

  • DrugPrednisone

    60 mg/m2 D1 to D21

  • DrugVincristin

    1.5 mg/m2 D1, D8, D15 and D22

  • DrugDaunorubicin

    40 mg/m2 D1, D8, D15 and D22

  • DrugPeg-asparaginase

    2000 UI/m2 D12 and D26

  • DrugIntrathecal Suspension

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

  • DrugCyclophosphamide

    1000 mg/m2 D36 and D64

  • DrugCytarabine

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

  • DrugMercaptopurine

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

  • DrugMethotrexate

    3.000 mg/m2 D8, D22, D36 and D50

  • DrugDoxorubicin

    30 mg/m2 D1 and D22

05

What researchers measure

Primary outcomes

  1. Overall survival (OS)

    cumulative proportion of patients alive (considering the time between the date of diagnosis and death or last follow-up)

    Time frame: 4 years

Secondary outcomes

  1. Event-free survival (EFS)

    time between enrollment in the study and the occurrence of any event: refractoriness after the first two cycles of induction, death or relapse.

    Time frame: 4 years

  2. Early death rate

    proportion of patients who died before the first bone marrow evaluation of response (after induction I)

    Time frame: 60 days

  3. Complete response rate

    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

    Time frame: 60 days

  4. Cumulative incidence of relapse

    rate of disease relapse after CR calculated considering death as a competing event.

    Time frame: 4 years

  5. HSCT rate

    proportion of patients eligible for the protocol who were able to perform the procedure in their first CR

    Time frame: 2 years

06

Study locations

1 of 1 sites recruiting
  • Instituto do Cancer do Estado de Sao Paulo
    São Paulo, SP 01246000, Brazil
    Recruiting
07

References and documents

Publications

  • 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. PubMed 35344469 ↗

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT05959720
Lead sponsor
Instituto do Cancer do Estado de São Paulo
Collaborators
Servier
Responsible party
Wellington Fernandes (Principal Investigator, Instituto do Cancer do Estado de São Paulo) — Principal investigator
First posted
Jul 25, 2023
Start date
Sep 5, 2023
Primary completion
Jun 2028 (estimated)
Completion
Jun 2030 (estimated)
Last update
May 7, 2025

Study contacts

Graziela Silva
Contact
graziela.sasilva@hc.fm.usp.br
551138934677
Bruna Moraes, MSc
Contact
pesquisa.hematologia@hc.fm.usp.br
551126628112
Wellington F Silva, MD PhD
principal investigator · Instituto do Cancer do Estado de São Paulo
Eduardo M Rego, MD PhD
study chair · Instituto do Cancer do Estado de São Paulo

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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