Genetic Polymorphisms in Drug Induced Neuropathy in Children With ALL

NCT05811910 | Unknown

• 1 other identifier: 58/22
• Study Type: observational
• Target: 290
• Locations: 1 country
• Sites: 1

Brief Summary

Therapeutic success in childhood ALL reaches an outstanding success that currently relies upon risk stratification of patients with appropriate modulation of chemotherapy intensity based on underlying blasts' biological and molecular characteristics, and depth of initial treatment response. ALL polychemotherapeutic approaches share similar therapeutic scheme, with more intensive and toxic earlier phases (about 6 months) followed by a prolonged immunosuppressive regimen for maintenance (about 18 months). Protocols comprise glucocorticoids, antimetabolites, asparaginase, alkylating agents, antimitotic drugs antibiotics and, in case of Philadelphia positive ALL, anti-tyrosine kinase inhibitors combined together at different dosages and timing according to the patient's class of risk. ALL chemotherapeutic agents can damage nearly all organs. Some adverse reactions are extensions of the drugs' desired pharmacological effects on bone marrow and affect almost all children. Other adverse effects occur unpredictably in a smaller fraction of patients who, for unknown reasons, are more susceptible. Concerns about chemotherapy-related toxicities generated a significant need of finding predictive markers for the a priori identification of at-risk patients. Pharmacogenomics markers can be useful tools in clinics for tailoring therapy intensity on patients' genetic profile and in basic research for better understanding mechanistic and regulatory pathways of the biological functions associated with ALL treatment toxicities. Several genome wide association studies explored the landscape of ALL treatment-associated toxicities, discovering the contribution of important variants. Among these, TPMT single nucleotide polymorphisms (SNPs) have a well-recognized role in thiopurine-induced myelotoxicity. SNP rs924607 (C\>T) in the promoter region of the gene encoding for the centrosomal protein 72 (CEP72) was associated with increased risk and severity of vincristine-related peripheral neuropathy. The aim of this study is to perform a GWAS in ALL children to provide insight into genetic loci affecting the occurrence of severe (grade III-V) vincristine-related peripheral neuropathy during induction therapy in the AIEOP protocols.

Conditions

Acute Lymphocytic Leukemia

Keywords

Acute lymphoblastic leukemia; GWAS; Toxicities

Outcome Measures

Primary Outcomes (1)

• To identify genetic loci affecting the occurrence of severe (grade III-V) vincristine-related peripheral neuropathy during induction therapy in the AIEOP-BFM protocols

  Toxicities will be assessed by clinicians using the National Cancer Institute Common Terminology Criteria for Adverse Events and graded as mild (grade I), moderate (grade II), serious/disabling (grade III), life-threatening (grade IV) or lethal (grade V). DNA will be genotyped by the lnfinium Omni2.5 BeadChip (Illumina) for a total number of markers of -2000000 SNP

  At the end of the 2 year study period

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Children aged 1-17 years with ALL

You may qualify if:

• Age \>=1 year and \<18 years old
• Newly diagnosed acute lymphoblastic leukemia (ALL)
• No Ph+ (BCR/ABL or t(9;22)-positive) ALL
• More than 4 weeks since prior steroids
• Written informed consent

You may not qualify if:

• Secondary ALL
• Prior disease that would preclude treatment with chemotherapy
• Evidence of pregnancy or lactation period
• Participation in another clinical study

Sponsors & Collaborators

• IRCCS Burlo Garofolo: lead

Study Sites (1)

IRCCS materno infantile Burlo Garofolo

Trieste, Friuli Venezia Giulia, 34137, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

blood samples

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Marco Rabusin, MD

  IRCCS materno infantile Burlo Garofolo

  STUDY DIRECTOR

Central Study Contacts

Marco Rabusin, MD

CONTACT

+39 0403785111; marco.rabusin@burlo.trieste.it

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2023
• First Posted: April 13, 2023
• Study Start: March 30, 2021
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: April 13, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)