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

Cytochrome P450 Inhibition With Ketoconazole to Decrease Dosage and Costs of Dasatinib for Chronic Myelogenous Leukemia

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.

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.

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)