Pharmacokinetic Study of Venetoclax Tablets Crushed and Dissolved Into a Solution

Official title

A Pharmacokinetic Study of Venetoclax Tablets Crushed and Dissolved Into a Solution in Children and Young Adults With Hematologic Malignancies

Overview

The use of venetoclax-based therapies for pediatric patients with relapsed or refractory malignancies is increasingly common outside of the clinical trial setting. For patients who cannot swallow tablets, it is common to crush the tablets and dissolve them in liquid to create a solution. However, no PK data exists in adults or children using crushed tablets dissolved in liquid in this manner, and as a result, the venetoclax exposure with this solution is unknown. Primary Objectives • To determine the pharmacokinetics of venetoclax when commercially available tablets are crushed and dissolved into a solution Secondary Objectives * To evaluate the safety of crushed venetoclax tablets administered as an oral solution * To determine the pharmacokinetics of venetoclax solution in patients receiving concomitant strong and moderate CYP3A inhibitors * To determine potential pharmacokinetic differences based on route of venetoclax solution administration (ie. PO vs NG tube vs G-tube) * To determine the concentration of venetoclax in cerebral spinal fluid when administered as an oral solution

Detailed description

Peripheral blood will be drawn at multiple time points to evaluate venetoclax pharmacokinetics in patients who are receiving venetoclax solution made from crushed tablets as part of their oncology treatment.

Interventions

• Other 1. Drug: The Venetoclax PK study is collecting bodily fluid samples (ie., whole blood and optional cerebrospinal fluid) of patients prescribed venetoclax as crushed tablets per standard of care.
  Participants will receive Venetoclax as prescribed by their treating provider as part of their clinical care.

Primary outcome measures

• Clearance (CL) as measured by PK sampling (Peripheral Blood; Required) [Time frame: Blood will be collected on one PK day between Days 5-12 after completion of the venetoclax dose ramp-up : within 1hr prior to the administration of venetoclax, then 2hrs, 5hrs, 12hrs, 18hrs and 24hrs after the administration of venetoclax.]
• Clearance (CL) as measured by PK sampling (Peripheral Blood; Required) [Time frame: Blood will be collected on one PK day between Days 5-12 after completion of the venetoclax dose ramp-up : within 1hr prior to the administration of venetoclax, then 2hrs, 5hrs, 12hrs, 18hrs and 24hrs after the administration of venetoclax.]
• Clearance (CL) as measured by PK sampling (Peripheral Blood; Required) [Time frame: Blood will be collected on one PK day between Days 5-12 after completion of the venetoclax dose ramp-up : within 1hr prior to the administration of venetoclax, then 2hrs, 5hrs, 12hrs, 18hrs and 24hrs after the administration of venetoclax.]
• Clearance (CL) as measured by PK sampling (Peripheral Blood; Required) [Time frame: Blood will be collected on one PK day between Days 5-12 after completion of the venetoclax dose ramp-up : within 1hr prior to the administration of venetoclax, then 2hrs, 5hrs, 12hrs, 18hrs and 24hrs after the administration of venetoclax.]
• Clearance (CL) as measured by PK sampling (Peripheral Blood; Required) [Time frame: Blood will be collected on one PK day between Days 5-12 after completion of the venetoclax dose ramp-up : within 1hr prior to the administration of venetoclax, then 2hrs, 5hrs, 12hrs, 18hrs and 24hrs after the administration of venetoclax.]
• Clearance (CL) as measured by PK sampling (Peripheral Blood; Required) [Time frame: Blood will be collected on one PK day between Days 5-12 after completion of the venetoclax dose ramp-up : within 1hr prior to the administration of venetoclax, then 2hrs, 5hrs, 12hrs, 18hrs and 24hrs after the administration of venetoclax.]
• Clearance (CL) as measured by PK sampling (Cerebrospinal Fluid; Optional) [Time frame: Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points.]
• Clearance (CL) as measured by PK sampling (Cerebrospinal Fluid; Optional) [Time frame: Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points.]
• Clearance (CL) as measured by PK sampling (Cerebrospinal Fluid; Optional) [Time frame: Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points.]
• Clearance (CL) as measured by PK sampling (Cerebrospinal Fluid; Optional) [Time frame: Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points.]

Eligibility criteria

Inclusion criteria

• Age: Patients must be <39 years of age at time of study enrollment
• Diagnosis: Patients may have a diagnosis of any hematologic malignancy
• Central access: Patients must have an existing venous or arterial access line for PK blood draws
• Weight requirement: Patients must weigh at least 5.5 kg at the time of enrollment
• Venetoclax: Patients must be receiving any dose of venetoclax given as a solution made from crushed tablets by mouth (PO) or via nasogastric (NG), or G-tube as prescribed by their treating oncologist.
• Concurrent chemotherapy medications: Patients may receive venetoclax as a single agent or in combination with any other chemotherapeutic agents.

Exclusion criteria

• Pregnant women are excluded from this study because venetoclax has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with venetoclax, breastfeeding should be discontinued if the mother is treated with venetoclax.
• Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method while on study treatment and for six months following completion.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Other

Study locations

United States · 5 centers

• Children's Hospital Colorado — Aurora
• Cincinnati Children's Hospital Medical Center — Cincinnati
• Children's Hospital of Philadelphia — Philadelphia
• Texas Children's Hospital — Houston
• Children's Hospital of Wisconsin — Milwaukee

Identifiers

NCT: NCT06131801 · Venetoclax PK

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗