Vincristine Pharmacokinetics in Infants

NCT05359237 | Active Not Recruiting FDA Drug

• 3 other identifiers: PEPN22P1NCI-2022-03576UM1CA228823
• Study Type: observational
• Target: 83
• Locations: 3 countries
• Sites: 29

Brief Summary

This pilot trial compares drug exposure levels using a new method for dosing vincristine in infants and young children compared to the standard dosing method based on body surface area (BSA) in older children. Vincristine is an anticancer drug used to a variety of childhood cancers. The doses anticancer drugs in children must be adjusted based on the size of the child because children vary significantly in size (height, weight, and BSA) and ability to metabolize drugs from infancy to adolescence. The dose of most anticancer drugs is adjusted to BSA, which is calculated from a patient's weight and height. However, infants and young children have more severe side effects if the BSA is used to calculate their dose, so new dosing models have to be made to safely give anticancer drugs to the youngest patients. This new method uses a BSA-banded approach to determine the dose. Collecting blood samples before and after a dose of the drug will help researchers determine whether this new vincristine dosing method results in equivalent drug levels in the blood over time in infants and young children compared to older children.

Conditions

Hematopoietic and Lymphoid Cell Neoplasm; Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• Area under the concentration time curve for the elimination phase (AUCelim) by age group

  Estimate (95% CI) of the mean area under the concentration time curve for the elimination phase assessed at 0, 2, 6-8, and 18-24 hours after vinCRISTine dose by age group.

  Up to 24 hours post vincristine dose

Secondary Outcomes (1)

• Intra- and inter-age coefficient of variation (CV)

  Up to 42 days

Other Outcomes (2)

• Correlation of AUC for the elimination phase with CYP3A4 and CYP3A5 single nucleotide polymorphisms (SNPs)

  Up to 24 hours

• Number of patients requiring vincristine dose modifications

  Up to 42 days

Study Arms (1)

Observational (SOC vincristine, biospecimen collection)

Patients receive vincristine IV per SOC. Patients undergo collection of blood samples at baseline (before first vincristine dose), and 2, 6-8, and 18-24 hours after a dose of vincristine. Patients may also undergo collection of blood samples with a second SOC vincristine dose at the same time points.

Procedure: Biospecimen Collection; Drug: Vincristine

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Observational (SOC vincristine, biospecimen collection)

Vincristine DRUG

Given IV per standard of care

Also known as: LCR, Leurocristine, VCR, Vincrystine

Observational (SOC vincristine, biospecimen collection)

Eligibility Criteria

• Age: Up to 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Infants and young children receiving treatment regimen that includes vinCRIStine

You may qualify if:

• Patients must be =\< 12 years of age at the time of study enrollment. Patients will be stratified into 4 age groups:
• to 6 months
• months and 1 day to 12 months
• months and 1 day to 36 months
• months and 1 day to 12 years with a BSA ≥ 0.6 m\^2
• Newly diagnosed and relapsed cancer diagnosis that is being treated with vinCRIStine at the 1.5 mg/m\^2 dose level
• Any disease status
• Patients must have a Lansky performance status of 50 or higher
• Patients must be receiving a treatment regimen that includes 1.5 mg/m\^2 vinCRIStine (maximum dose 2 mg)
• Patients with a BSA \< 0.6 m\^2 must be dosed according to the Children's Oncology Group (COG) BSA-banded infant dosing table for the 1.5mg/m2 dose level for vinCRIStine
• Note: Patients can be studied after any dose of vinCRIStine
• Patients who are NOT enrolled on a COG clinical trial and who have a BSA \< 0.6 m\^2 and who are being dosed according to another infant dosing method (e.g., the 30-Rule) can receive a dose of vinCRIStine from the infant dosing table for the pharmacokinetic study. These patients will NOT be part of the Dose Modification Assessment
• Patients with a seizure disorder may be enrolled if on allowable anticonvulsants and well controlled as evidenced by no increase in seizure frequency in the prior 7 days
• Nervous system toxicities (Common Terminology Criteria for Adverse Events \[CTCAE\]) version (v)5 resulting from prior therapy must be grade =\< 2
• Central venous access device in place (e.g., percutaneous indwelling central catheter \[PICC\], port, Broviac) or scheduled to be placed prior to the dose of vinCRIStine and that can be used for pharmacokinetic (PK) sampling

You may not qualify if:

• Azoles antifungals and macrolide antibiotics: Patients who are currently receiving an azole or macrolide (e.g., fluconazole, isavuconazole, itraconazole, posaconazole, voriconazole, ketoconazole, eryromycin, clarithromycin, azithromycin, roxithromycin, or telithromycin) are not eligible
• CYP3A4/5 inducers/inhibitors: Patients receiving any medications or substances that are considered moderate or strong inhibitors or inducers of CYP3A4/5 are not eligible. Moderate or strong inducers or inhibitors of CYP3A4/5 should be avoided from 14 days prior to enrollment to the end of the study.
• Note the following are allowed:
• Dexamethasone for CNS tumors or metastases, on a stable dose
• Aprepitant for management of nausea and vomiting
• Anticonvulsants: Patients receiving moderate or strong CYP3A4/5 enzyme inducing anticonvulsants are not eligible.
• Patients with Charcot-Marie-Tooth disease
• A baseline neurological disorder with manifestations that overlap with vinCRIStine-associated neurotoxicities
• Patients being treated on a Children Oncology Group (COG) clinical trial, that does not use the infant dosing tables for vinCRIStine are not eligible for this study.
• Patients receiving a modified dose (\< 1.5 mg/m\^2) of vinCRIStine due to prior toxicity
• Patients who in the opinion of the investigator may not be able to comply with the sampling requirements of the study

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (29)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Queensland Children's Hospital

South Brisbane, Queensland, 4101, Australia

Location

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

Specimen Handling; Vincristine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Emily Blauel

  Pediatric Early Phase Clinical Trial Network

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2022
• First Posted: May 3, 2022
• Study Start: November 16, 2022
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: February 6, 2026

Record last verified: 2026-02

Locations

US (27); AU (1); CA (1)