Clinical trial NCT04271215: Overweight and Obesity as Prognostic Factors for Survival in Children With Acute Lymphoblastic Leukemia
Official title: Overweight and Obesity as Prognostic Factors for Survival in Children With Acute Lymphoblastic Leukemia
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Leukemia, Lymphoblastic
Keywords: Overweight
Obesity
Survival
Children
Lead sponsor: Coordinación de Investigación en Salud, Mexico
Sponsor class: OTHER_GOV
First posted: 2020-02-17
Enrollment: 1200
Sex: ALL
Minimum age (years): 1
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study variables and data will be collected from the clinical files. The information collected by the surveyors will be delivered weekly to our Research Unit, where the field work coordinators will be in charge of assigning them a folio number, reviewing the collection instrument and passing it on to the personnel in charge of capturing the information. In addition, the fieldwork coordinators will supervise the collection of information, the search for files in the archive, the capture of information and will be responsible for keeping the project's database up to date.

Brief summary: Background: Mexico City has one of the highest incidences and mortality rates of acute lymphoblastic leukemia (ALL) in the world and a high frequency of early relapses (17%) and early mortality (15%). Otherwise, childhood overweight and obesity are reaching epidemic proportions. They have been associated with poor outcomes in children with ALL. The aim of present study is to identify if overweight and obesity are prognostic factors associated with survival rates in Mexican children with ALL. Methods: Multicenter cohort study. ALL children younger than 15 years old are included and followed-up. Overweight and obesity are classified according World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) criteria. Deaths and relapses are the main outcomes.

Detailed description: Data collection Information regarding sex, age at diagnosis, place of residence, white blood cell (WBC) count, immunophenotype (B or T lineage), weight and height (length when appropriate) at diagnosis, and chemotherapy protocol is collected from the patients' clinical charts by previously standardized staff. Overcrowding was used as a proxy for socioeconomic status (SES) according to the Bronfman's criteria (high SES, up to 1.5 people per room; medium-low SES, more than 1.6 people per room). The risk classification is according to the criteria of the National Cancer Institute (NCI): standard risk \[ages from 1 to 9.99 years; WBC count \< 50 × 109/L\] or as high risk \[age \< 1 or ≥ 10 years or WBC ≥ 50 × 109/L\].

Assessment of nutritional status at diagnosis of ALL BMI at diagnosis will be used.. Using WHO software (version 3.2.2, World Health Organization, Geneva), the BMI-for-age Z-scores were calculated for each patient. According to WHO classification, patients were categorized as normal (- 1.9999 to 0.9999), wasted (- 2 to - 2.9999), severely wasted (≥ - 3), at risk of overweight (1-1.9999), overweight (2 to 2.9999) and obesity (≥3). In addition, the BMI percentiles cutoffs provided by CDC were: normal (p5-84.9999), underweight (\< p5), overweight (p85-94.9999), and obese (≥ p95). The nutritional classification and measurements validation regarding weight and height recorded in clinical files used to classify patients' nutritional status in present research has been previously described. Underweight patients were excluded from the analyses.

Sample size The sample size calculation was performed using Epi-Info version 7 software taking into account a mortality outcome frequency of 10.8% in the unexposed group (normal weight patients) and a death outcome frequency of 24% for the exposed (obese/overweight patients), a statistical power of 80% and a confidence of 95%; resulting in a total "n" of 350 overweight/obese patients to be compared with the rest of the cohort that are not overweight and obese.

Statistical analysis Descriptive statistics and relative risks (RR) calculation with 95% confidence intervals (CI) will be carried out. Kaplan-Meier survival analysis will be conducted. Log-rank test will be calculated. The analyses will be conducted independently for disease-free-survival (DFS) or overall survival (OS), adjusting for variables whose effects on the studied outcomes have been previously documented (age, sex, socioeconomic status, immunophenotype, NCI risk classification, and chemotherapy protocol). A Cox proportional hazard model will be used. Hazard ratios (HR) with 95% CIs will be calculated.

Eligibility criteria: Inclusion Criteria:

* Patients under 15 years of age
* Newly diagnosed with acute lymphoblastic leukemia
* Diagnosis confirmation by bone marrow aspiration and immunophenotype
* Attended in the participating Hospitals.

Exclusion Criteria:

- Patients with Down Syndrome (for being a population with different disease behavior and cytogenetic alterations than patients without this genetic condition)

Primary outcomes:
measure: Overall survival
timeFrame: year 5
measure: Disease-free survival
timeFrame: year 5
Secondary outcomes:
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Centro Médico Nacional Hospital General La Raza, IMSS
city: Mexico City
country: Mexico
facility: Hospital General Regional Num 1 Carlos McGregor Sánchez Navarro, IMSS
city: Mexico City
country: Mexico
facility: Hospital de Pediatria "Dr. Silvestre Frenk Freund" CMN Siglo XXI, IMSS
Study officials:
affiliation: Instituto Mexicano del Seguro Social/Instituto Nacional de Medicina Genomica
name: Juan M Mejía-Arangure, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nunez-Enriquez JC, Gil-Hernandez AE, Jimenez-Hernandez E, Fajardo-Gutierrez A, Medina-Sanson A, Flores-Lujano J, Espinoza-Hernandez LE, Duarte-Rodriguez DA, Amador-Sanchez R, Penaloza-Gonzalez JG, Torres-Nava JR, Espinosa-Elizondo RM, Flores-Villegas LV, Merino-Pasaye LE, Perez-Saldivar ML, Dorantes-Acosta EM, Cortes-Herrera B, Solis-Labastida KA, Nunez-Villegas NN, Velazquez-Avina MM, Rangel-Lopez A, Gonzalez-Avila AI, Santillan-Juarez JD, Garcia-Velazquez AJ, Jimenez-Morales S, Bekker-Mendez VC, Rosas-Vargas H, Mata-Rocha M, Sepulveda-Robles OA, Martin-Trejo JA, Mejia-Arangure JM. Overweight and obesity as predictors of early mortality in Mexican children with acute lymphoblastic leukemia: a multicenter cohort study. BMC Cancer. 2019 Jul 18;19(1):708. doi: 10.1186/s12885-019-5878-8.