Trial Title:
Adult Acute Lymphoblastic Leukemia Treated With Pediatric Regimen in Brazil
NCT ID:
NCT05959720
Condition:
Acute Lymphoid Leukemia
Minimal Residual Disease
Gene Abnormality
Chemotherapeutic Toxicity
Conditions: Official terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasm, Residual
Cytarabine
Prednisone
Cyclophosphamide
Doxorubicin
Methotrexate
Daunorubicin
Asparaginase
Mercaptopurine
Pegaspargase
Study type:
Observational [Patient Registry]
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
Intervention:
Intervention type:
Drug
Intervention name:
Prednisone
Description:
60 mg/m2 D1 to D21
Arm group label:
Eligible patients
Intervention type:
Drug
Intervention name:
Vincristin
Description:
1.5 mg/m2 D1, D8, D15 and D22
Arm group label:
Eligible patients
Intervention type:
Drug
Intervention name:
Daunorubicin
Description:
40 mg/m2 D1, D8, D15 and D22
Arm group label:
Eligible patients
Intervention type:
Drug
Intervention name:
Peg-asparaginase
Description:
2000 UI/m2 D12 and D26
Arm group label:
Eligible patients
Intervention type:
Drug
Intervention name:
Intrathecal Suspension
Description:
MTX 12 mg, Dexamethasone 2 mg, Cytarabine 60 mg D1, D8, D15, D22, D29
Arm group label:
Eligible patients
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
1000 mg/m2 D36 and D64
Arm group label:
Eligible patients
Intervention type:
Drug
Intervention name:
Cytarabine
Description:
75 mg/m2 D36 to D39, D43 to D46, D50 to D53 and D57 to D60
Arm group label:
Eligible patients
Intervention type:
Drug
Intervention name:
Mercaptopurine
Description:
30 mg/m2 D36 to D63 and D1 to D56 of consolidation
Arm group label:
Eligible patients
Intervention type:
Drug
Intervention name:
Methotrexate
Description:
3.000 mg/m2 D8, D22, D36 and D50
Arm group label:
Eligible patients
Intervention type:
Drug
Intervention name:
Doxorubicin
Description:
30 mg/m2 D1 and D22
Arm group label:
Eligible patients
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.
Criteria for eligibility:
Study pop:
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.
Sampling method:
Non-Probability Sample
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
Gender:
All
Minimum age:
16 Years
Maximum age:
50 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Instituto do Cancer do Estado de Sao Paulo
Address:
City:
São Paulo
Zip:
01246000
Country:
Brazil
Status:
Recruiting
Contact:
Last name:
Wellington F Silva, MD PhD
Phone:
551138944677
Email:
wellington.fernandes@hc.fm.usp.br
Start date:
September 5, 2023
Completion date:
June 2030
Lead sponsor:
Agency:
Instituto do Cancer do Estado de São Paulo
Agency class:
Other
Collaborator:
Agency:
Servier
Agency class:
Industry
Source:
Instituto do Cancer do Estado de São Paulo
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05959720
