Clinical trial NCT05959720: Adult Acute Lymphoblastic Leukemia Treated With Pediatric Regimen in Brazil
Official title: Adult Acute Lymphoblastic Leukemia Treated With Pediatric Regimen in Brazil - a Prospective Collaborative Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Acute Lymphoid Leukemia
Minimal Residual Disease
Gene Abnormality
Chemotherapeutic Toxicity
Lead sponsor: Instituto do Cancer do Estado de São Paulo
Sponsor class: OTHER
Collaborators: name: Servier
First posted: 2023-07-25
Enrollment: 180
Sex: ALL
Minimum age (years): 16
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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

Primary outcomes:
measure: Overall survival (OS)
timeFrame: 4 years
Secondary outcomes:
measure: Event-free survival (EFS)
timeFrame: 4 years
measure: Early death rate
timeFrame: 60 days
measure: Complete response rate
timeFrame: 60 days
measure: Cumulative incidence of relapse
timeFrame: 4 years
measure: HSCT rate
timeFrame: 2 years
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo
state: SP
Study officials:
affiliation: Instituto do Cancer do Estado de São Paulo
name: Wellington F Silva, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto do Cancer do Estado de São Paulo
name: Eduardo M Rego, MD PhD
role: STUDY_CHAIR
References:
citation: 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.