Clinical trial NCT06131801: 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hematologic Malignancy
Leukemia
Lymphoma
Acute Lymphocytic Leukemia
ALL
Acute Myelogenous Leukemia
AML
Chronic Myelogenous Leukemia
CML
Myeloproliferative Neoplasm
Non Hodgkin Lymphoma
Hodgkin Lymphoma
Diffuse Large B Cell Lymphoma
Follicular Lymphoma
Burkitt Lymphoma
T-cell Lymphoma
B Cell Lymphoma
Peripheral T Cell Lymphoma
Cutaneous B-Cell Lymphoma
Keywords: Venetoclax
Pediatric AML
Pediatric Relapsed/Refractory AML
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
First posted: 2023-11-14
Enrollment: 30
Sex: ALL
Minimum age (years): 0
Maximum age (years): 38
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
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.

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

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.

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.

Primary outcomes:
measure: Clearance (CL) as measured by PK sampling (Peripheral Blood; Required)
timeFrame: 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.
measure: Clearance (CL) as measured by PK sampling (Peripheral Blood; Required)
timeFrame: 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.
measure: Clearance (CL) as measured by PK sampling (Peripheral Blood; Required)
timeFrame: 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.
measure: Clearance (CL) as measured by PK sampling (Peripheral Blood; Required)
timeFrame: 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.
measure: Clearance (CL) as measured by PK sampling (Peripheral Blood; Required)
timeFrame: 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.
measure: Clearance (CL) as measured by PK sampling (Peripheral Blood; Required)
timeFrame: 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.
measure: Clearance (CL) as measured by PK sampling (Cerebrospinal Fluid; Optional)
timeFrame: Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points.
measure: Clearance (CL) as measured by PK sampling (Cerebrospinal Fluid; Optional)
timeFrame: Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points.
measure: Clearance (CL) as measured by PK sampling (Cerebrospinal Fluid; Optional)
timeFrame: Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points.
measure: Clearance (CL) as measured by PK sampling (Cerebrospinal Fluid; Optional)
timeFrame: Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points.
measure: Clearance (CL) as measured by PK sampling (Cerebrospinal Fluid; Optional)
timeFrame: Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points.
measure: Clearance (CL) as measured by PK sampling (Cerebrospinal Fluid; Optional)
timeFrame: Around Days 8, 15, 22, and/or 28, all +/- 3 days. Not all patients will have CSF collected at these time points.
Secondary outcomes:
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Lauren Pommert, MD
role: PRINCIPAL_INVESTIGATOR
References: