Chronic Myeloid Leukemia, Chronic Phase
Conditions
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.
Interventions
DRUGDasatinib Pill
Patients will receive half pill of dasatinib 50mg (25mg/day, orally) for one year
Patients will receive ketoconazole 200mg two times a day, orally, for one year.
Sponsors
Fernando De la Garza Salazar
Hospital Universitario Dr. Jose E. Gonzalez
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| The rate of sustained Molecular Response (MR4.5) | Up to 12 months | Log reduction in BCR/ABL of 4.5 |
| 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 Complete Cytogenetic Response | Up to 12 months | BCR/ABL IS \<=1% at 12 months |
Countries
Mexico
Contacts
Primary ContactFernando De la Garza Salazar, MD
Outcome results
None listed