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

Phase 2

Recruiting

• Conditions: Chronic Myeloid Leukemia, Chronic Phase
• Interventions: Drug: Dasatinib Pill; Drug: Ketoconazole Pill

• Registration Number: NCT05638763
• Lead Sponsor: Hospital Universitario Dr. Jose E. Gonzalez

Brief Summary

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.

Detailed 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.

Study Timeline

• Status Verified: 2022-11
• Study First Submitted: 2022-11-16
• Study First Submitted QC: 2022-11-25
• Last Update Submitted: 2022-11-25
• Study First Posted: 2022-12-06
• Last Update Posted: 2022-12-06
• Study Start: 2024-11
• Primary Completion: 2024-11
• Study Completion: 2024-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 15

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dasatinib and ketoconazole	Dasatinib Pill	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.
Dasatinib and ketoconazole	Ketoconazole Pill	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.

Primary Outcome Measures

Name	Time	Method
The rate of Complete Cytogenetic Response	Up to 6 months	B-cell antigen receptor(BCR)/Tyrosine-protein kinase-ABL1(ABL1) IS \<=1% at 6 months

Secondary Outcome Measures

Name	Time	Method
The proportion of non hematological side effects	Up to 12 months	Proportion of patients that presented non hematological side effects to the intervention
The rate of sustained Molecular Response (MR4.5)	Up to 12 months	Log reduction in BCR/ABL of 4.5
The rate of Complete Cytogenetic Response	Up to 12 months	BCR/ABL IS \<=1% at 12 months
The rate of Molecular Response (MR4)	Up to 6 months	Log reduction in BCR/ABL of 4
The rate of Molecular Response (MR4.5)	Up to 6 months	Log reduction in BCR/ABL of 4.5

Trial Locations

Locations (1)

Hospital Universitario Dr. José Eleuterio González; 🇲🇽 Monterrey, Nuevo Leon, Mexico