Pharmacokinetic Study of Venetoclax Tablets Crushed and Dissolved Into a Solution

NCT06131801 | Recruiting DMC FDA Drug

• 1 other identifier: Venetoclax PK
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 5

Brief Summary

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

Conditions

Myeloproliferative Neoplasm; Non Hodgkin Lymphoma; Hodgkin Lymphoma; Follicular Lymphoma; Burkitt Lymphoma; T-cell Lymphoma; B Cell Lymphoma; Peripheral T Cell Lymphoma; Cutaneous B-Cell Lymphoma; Diffuse Large B Cell Lymphoma; Hematologic Malignancy; Leukemia; Lymphoma; Acute Lymphocytic Leukemia; ALL; Acute Myelogenous Leukemia; AML; Chronic Myelogenous Leukemia; CML

Keywords

Venetoclax; Pediatric AML; Pediatric Relapsed/Refractory AML

Outcome Measures

Primary Outcomes (12)

• Clearance (CL) as measured by PK sampling (Peripheral Blood; Required)

  PK parameters of venetoclax will be described in peripheral blood including: the observed peak plasma concentration (Cmax)

  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)

  PK parameters of venetoclax will be described in peripheral blood including: the time to peak (Tmax)

  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)

  PK parameters of venetoclax will be described in peripheral blood including: the apparent terminal phase elimination rate constant (β)

  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)

  PK parameters of venetoclax will be described in peripheral blood including: the terminal-phase elimination half-life (T1/2)

  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)

  PK parameters of venetoclax will be described in peripheral blood including: the areas under plasma concentration curve (AUC) over a 24-hour dose interval (AUC0-24) or for infinite time (AUC0-∞)

  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)

  PK parameters of venetoclax will be described in peripheral blood including: oral clearance (CL/F) of venetoclax

  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)

  PK parameters of venetoclax will be described in cerebral spinal fluid including: the observed peak plasma concentration (Cmax)

  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)

  PK parameters of venetoclax will be described in cerebral spinal fluid including: the time to peak (Tmax)

  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)

  PK parameters of venetoclax will be described in cerebral spinal fluid including: the apparent terminal phase elimination rate constant (β)

  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)

  PK parameters of venetoclax will be described in cerebral spinal fluid including: the terminal-phase elimination half-life (T1/2)

  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)

  PK parameters of venetoclax will be described in cerebral spinal fluid including: the areas under plasma concentration curve (AUC) over a 24-hour dose interval (AUC0-24) or for infinite time (AUC0-∞)

  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)

  PK parameters of venetoclax will be described in cerebral spinal fluid including: oral clearance (CL/F)

  Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points.

Study Arms (1)

Children and Young Adults

Children and Young Adults who are prescribed venetoclax made from crushed tablets as part of their clinical care.

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.

Interventions

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. OTHER

Participants will receive Venetoclax as prescribed by their treating provider as part of their clinical care.

Children and Young Adults

Eligibility Criteria

• Age: 0 Years - 38 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

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. Patients must be \<39 years of age at time of study enrollment.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (5)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

NOT YET RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood (1-2 mL) collected from an existing venous or arterial access line. Patients \< 14 kg (approximately 31 pounds) will be limited to 1 mL for each PK sample draw. OPTIONAL: An additional 3-4 mLs of cerebrospinal fluid (CSF) at any time point in which cerebrospinal fluid (CSF) is already being obtained as part of standard of care therapy.

MeSH Terms

Conditions

Hematologic Neoplasms; Leukemia; Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myeloproliferative Disorders; Lymphoma, Non-Hodgkin; Hodgkin Disease; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Burkitt Lymphoma; Lymphoma, T-Cell; Lymphoma, B-Cell; Lymphoma, T-Cell, Peripheral

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia, Myeloid; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Study Officials

• Lauren Pommert, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Site Public Contact

CONTACT

(513) 636-2799; cancer@cchmc.org

Study Design

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

Study Record Dates

• First Submitted: October 24, 2023
• First Posted: November 14, 2023
• Study Start: November 15, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: June 4, 2026

Record last verified: 2026-06

Locations

US (5)