Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04283955
Recruitment Status : Completed
First Posted : February 25, 2020
Last Update Posted : February 25, 2020
Sponsor:
Information provided by (Responsible Party):
Xiao-Fei Sun, Sun Yat-sen University

Brief Summary:
We hypothesized that polymorphism MTHFR C677T and A1298C should be associated with HD-MTX-related toxicities in children with NHL. Therefore, we aimed to retrospectively explore their relationships in this analysis.

Condition or disease Intervention/treatment
Pediatric NHL Drug: High-dose MTX based chemotherapy

Detailed Description:

INTRODUCTION: Non-Hodgkin lymphoma (NHL), the fourth most common malignancy across the pediatric age spectrum, is a heterogeneous group of lymphoid malignancies. In children, NHL comprises four main wide categories: lymphoblastic lymphoma (LBL), Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and anaplastic large cell lymphoma (ALCL). The current overall survival rate of pediatric NHL exceeds 80% due to dramatic progress in developing risk-adapted curative therapy (1), in which methotrexate (MTX) plays a crucial part.

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.

Layout table for study information
Study Type : Observational
Actual Enrollment : 93 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: 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
Actual Study Start Date : March 1, 2014
Actual Primary Completion Date : March 1, 2019
Actual Study Completion Date : March 1, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma


Intervention Details:
  • Drug: 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.


Primary Outcome Measures :
  1. Observations of HD-MTX-related toxicities [ Time Frame: 3 weeks ]
    We recorded the toxicities that occurred to the patients after the MTX infusion, including hematological suppression, hepatotoxicity, nephrotoxicity, oral mucositis, vomiting and diarrhea.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
  1. Age:≤ 18 years old;
  2. Diseases: 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)
  3. Treatment: HD-MTX-based chemotherapy at the dose of 5g/m2;
  4. Genotype: MTHFR C677T and A1298C;
  5. Center:Sun Yat-sen University Cancer Center,Guangzhou, P.R China;
  6. Time period: between March 2014 and March 2019.
Criteria

Inclusion Criteria: patients who were:

  • Aged ≤ 18 years old;
  • 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: patients who were:

  • Aged >18 years old;
  • 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 .

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04283955


Locations
Layout table for location information
China, Guangdong
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, China, 510060
Sponsors and Collaborators
Sun Yat-sen University

Layout table for additonal information
Responsible Party: Xiao-Fei Sun, MD, Sun Yat-sen University
ClinicalTrials.gov Identifier: NCT04283955    
Other Study ID Numbers: SCCCG-NHL-2017
First Posted: February 25, 2020    Key Record Dates
Last Update Posted: February 25, 2020
Last Verified: February 2020
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors