Vincristine Pharmacokinetics in Infants

NCT ID: NCT05359237

Last Updated: 2025-11-04

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 83 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-11-16
• Study Completion Date: 2025-12-31

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.

Detailed Description

PRIMARY OBJECTIVE:

I. To validate body surface area (BSA)-banded infant dosing tables by comparing vinCRIStine drug exposure, defined as the area under the concentration-time curve for the elimination phase (AUCelim), in infants and young children dosed according to the table to older children dosed according to BSA.

SECONDARY OBJECTIVE:

I. To estimate intra- and inter-age group variability (CV) using non-compartmental analysis (NCA) and population pharmacokinetic (PK) methods.

EXPLORATORY OBJECTIVES:

I. To correlate higher AUCelim with the presence of functionally impaired single nucleotide polymorphisms (SNP) of CYP3A4 and CYP3A5.

II. To assess vinCRIStine dose modifications in infants receiving weekly vinCRIStine dosed according to the BSA-banded infant dosing tables.

OUTLINE:

Patients receive vincristine intravenously (IV) per standard of care (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.

Patients are followed for dose modifications for a period of 42 days (when receiving weekly dosing of vincristine).

Conditions

Hematopoietic and Lymphoid Cell Neoplasm; Malignant Solid Neoplasm

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo collection of blood samples

Vincristine

Intervention Type: DRUG

Given IV per standard of care

Interventions

Biospecimen Collection

Undergo collection of blood samples

Intervention Type: PROCEDURE

Vincristine

Given IV per standard of care

Intervention Type: DRUG

Other Intervention Names

Biological Sample Collection; Biospecimen Collected; Specimen Collection; LCR; Leurocristine; VCR; Vincrystine

Eligibility Criteria

Inclusion Criteria

• Patients must be =< 12 years of age at the time of study enrollment. Patients will be stratified into 4 age groups:

• 0 to 6 months
• 6 months and 1 day to 12 months
• 12 months and 1 day to 36 months
• 36 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
• VinCRIStine may be given as an outpatient, as long as all sample time points can be collected, which will require return for hour 24 sampling

Exclusion Criteria

• 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

• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Children's Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emily Blauel

Role: PRINCIPAL_INVESTIGATOR

Pediatric Early Phase Clinical Trial Network

Locations

Children's Hospital of Alabama

Birmingham, Alabama, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

Children's Hospital of Orange County

Orange, California, United States

UCSF Medical Center-Mission Bay

San Francisco, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Children's National Medical Center

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

Lurie Children's Hospital-Chicago

Chicago, Illinois, United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Riley Hospital for Children

Indianapolis, Indiana, United States

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

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

New York, New York, United States

New York Medical College

Valhalla, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Saint Jude Children's Research Hospital

Memphis, Tennessee, United States

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, United States

Seattle Children's Hospital

Seattle, Washington, United States

Queensland Children's Hospital

South Brisbane, Queensland, Australia

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, Canada

Countries

United States; Australia; Canada

Other Identifiers

NCI-2022-03576

Identifier Type: REGISTRY

Identifier Source: secondary_id

PEPN22P1

Identifier Type: OTHER

Identifier Source: secondary_id

PEPN22P1

Identifier Type: OTHER

Identifier Source: secondary_id

UM1CA228823

Identifier Type: NIH

Identifier Source: secondary_id

View Link

PEPN22P1

Identifier Type: -

Identifier Source: org_study_id