A Retrospective Cohort Study: The Influence of MTHFR C677T and A1298C on the High-dose Methotrexate-Related Toxicities in Pediatric Patients With Non-Hodgkin Lymphoma
NCT ID: NCT04283955
Last Updated: 2020-02-25
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
93 participants
OBSERVATIONAL
2014-03-01
2019-03-01
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Chemotherapy With Rituximab for Aggressive B-NHL in Children and Adolescents
NCT07168980
Individualized High Dose Methotrexate to Treat Cancer in Children Who Have a Significant Risk for Side Effects to Methotrexate
NCT02076997
Understanding Methotrexate Induced Gastrointestinal Intolerance in Juvenile Idiopathic Arthritis and Childhood Leukemia
NCT02528435
LBL-2016 for Children or Adolescents in China
NCT02845882
BNHL-2015 for Children or Adolescents in China
NCT02405676
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
MTX is used to treat a variety of cancers. A high-dose MTX (HD-MTX) regimen, referred to the administration of a dosage ranging from 0.5g/m2 to 12.0g/m2 or even higher, is commonly used to treat childhood acute lymphoblastic leukemia (ALL), lymphoma and pediatric osteosarcoma. Despite its wide range of therapeutic efficacy, the toxicities of HD-MTX including reversible myelosuppression, nausea, vomiting, diarrhea, hepatotoxicity, nephrotoxicity, neurotoxicity, and particularly oral mucositis should not be neglected. Accumulating pharmacogenetic studies have revealed that polymorphisms of enzymes involved in folate pathway could lead to variability in response to MTX and HD-MTX-related toxicities in various malignancies. The most two extensively studied SNPs of MTHFR in relation to the toxicities of MTX are the C677T variant (Ala222Val, rs1801133) and A1298C variant (Glu 429Ala, rs1801131), both dampening the enzyme activity by 40-70%.
However, limited evidence is available in pediatric NHL, with results varying considerably in different studies. Therefore, the aim of this retrospective study was to evaluate the influence of C677T and A1298C polymorphisms on HD-MTX-related toxicities in children with NHL treated according to BFM-modified protocols.
PATIENTS \& METHODS：We reviewed the medical records of all pediatric patients who were diagnosed as NHL and received HD-MTX-based chemotherapy at the dose of 5g/m2 in Sun Yat-sen University Cancer Center between March 2014 and March 2019. Data were analyzed by chi-square test.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
COHORT
RETROSPECTIVE
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
High-dose MTX based chemotherapy
Patients received MTX therapy at the dose of 5g/m2 for 24 hours. Each dose of HD-MTX therapy was followed by 6\~7 times of leucovorin rescue 12 hours after the end of MTX infusion, at the dose of 15 mg/ m2 every 6 hours. The plasma MTX levels were monitored at 0, 24, 48, 72 hours from the initiation of HD-MTX infusion. To maintain the urine pH at approximately 7\~8, intravenous hydration and alkalization at the dose of 1,500ml/ m2 per day were achieved 12 hours prior to the initiation of HD-MTX administration (D0) and 3,000ml/ m2 per day lasted for the following 3 days (D1 to D3). CF was used to rinse mouth to prevent oral mucositis from D1 to D3. We closely monitored the volume and pH of the urine via routine test from D0 to D4.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Diagnosed as the four main types of NHL, including lymphoblastic lymphoma (LBL), Burkitt's lymphoma (BL), anaplastic large cell lymphoma (ALCL), diffuse large B-cell lymphoma (DLBCL);
* Treated with HD-MTX therapy at the dose of 5g/m2;
* Genotyped by PCR following Sanger with respect to MTHFR C677T and A1298C
* With complete medical records.
Exclusion Criteria
* Diagnosed as cancer types other than the four main types of NHL;
* Treated with no HD-MTX therapy or at the dose other than 5g/m2;
* Not genotyped by PCR following Sanger with respect to MTHFR C677T and A1298C
* With incomplete medical records .
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Sun Yat-sen University
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Xiao-Fei Sun
MD
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, China
Countries
Review the countries where the study has at least one active or historical site.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
SCCCG-NHL-2017
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.