Cytochrome P450 Inhibition to Decrease Dosage of Dasatinib for Chronic Myelogenous Leukemia

Hospital Universitario Dr. Jose E. Gonzalez

Status and phase: Enrolling; Phase 2

Conditions: Chronic Myeloid Leukemia, Chronic Phase

Treatments: Drug: Ketoconazole Pill; Drug: Dasatinib Pill

Study type: Interventional

Funder types: Other

Identifiers

NCT05638763

HE22-00031

Details and patient eligibility

About

This phase 2 single-arm study aims to demonstrate the efficacy of strong cytochrome inhibition with ketoconazole to reduce dasatinib dosage for adults with chronic myelogenous leukemia. Researchers will describe response rates and adverse events.

Full description

Dasatinib is a second-generation tyrosine kinase inhibitor that is metabolized by the cytochrome P450. Dasatinib has shown efficacy in patients with chronic myelogenous leukemia. Standard-dose dasatinib is 50mg-140mg/day orally, continuously. However, when combined with a strong CYP3A4 inhibitor, a dose reduction of 75% is warranted.

This phase 2 single-arm study aims to demonstrate the efficacy of strong cytochrome inhibition with ketoconazole to reduce the dosage and costs of dasatinib for adults with chronic myelogenous leukemia. Researchers will describe cytogenetic and molecular response rates at 3, 6, and 12 months and adverse events (i.e., pleural effusion) associated with this strategy.

Enrollment: 15 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age >18 years
2. Chronic myeloid leukemia in chronic phase according to the World Health Organization 2016
3. Eastern Cooperative Oncology Group (ECOG) 0-2

Exclusion criteria

1. Chronic heart disease (NYHA III-IV)
2. Bleeding disorders not attributed to the hematological malignancy
3. Pregnancy
4. Lactation
5. Chronic myeloid leukemia in blast phase
6. Organic dysfunction (Marshall score ≥2)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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15 participants in 1 patient group

Dasatinib and ketoconazole

Experimental group

Description:

Patients will receive dasatinib at a dose of 25mg orally daily for one year and ketoconazole 200mg orally two times per day for one year.

Treatment:

Drug: Dasatinib Pill

Drug: Ketoconazole Pill