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

Study Overview
=================
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.

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

Conditions
-----------------
Chronic Myeloid Leukemia, Chronic Phase

Intervention / Treatment
-----------------
* Drug: Dasatinib Pill
* Drug: Ketoconazole Pill


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age >18 years Chronic myeloid leukemia in chronic phase according to the World Health Organization 2016 Eastern Cooperative Oncology Group (ECOG) 0-2 Exclusion Criteria: Chronic heart disease (NYHA III-IV) Bleeding disorders not attributed to the hematological malignancy Pregnancy Lactation Chronic myeloid leukemia in blast phase Organic dysfunction (Marshall score ≥2)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dasatinib and ketoconazole<br>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. | Drug: Dasatinib Pill<br>* Patients will receive half pill of dasatinib 50mg (25mg/day, orally) for one year<br>* Other names: Sprycel;Drug: Ketoconazole Pill<br>* Patients will receive ketoconazole 200mg two times a day, orally, for one year.<br>* Other names: Nizoral;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of Complete Cytogenetic Response | B-cell antigen receptor(BCR)/Tyrosine-protein kinase-ABL1(ABL1) IS <=1% at 6 months | Up to 6 months | 

Secondary Outcome Measures

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