Clinical trial NCT05638763: Cytochrome P450 Inhibition to Decrease Dosage of Dasatinib for Chronic Myelogenous Leukemia
Official title: Cytochrome P450 Inhibition With Ketoconazole to Decrease Dosage and Costs of Dasatinib for Chronic Myelogenous Leukemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Chronic Myeloid Leukemia, Chronic Phase
Lead sponsor: Hospital Universitario Dr. Jose E. Gonzalez
Sponsor class: OTHER
Collaborators: name: Fernando De la Garza Salazar
First posted: 2022-12-06
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: The rate of Complete Cytogenetic Response
timeFrame: Up to 6 months
Secondary outcomes:
measure: The rate of Molecular Response (MR4)
timeFrame: Up to 6 months
measure: The rate of Molecular Response (MR4.5)
timeFrame: Up to 6 months
measure: The rate of sustained Molecular Response (MR4.5)
timeFrame: Up to 12 months
measure: The proportion of non hematological side effects
timeFrame: Up to 12 months
measure: The rate of Complete Cytogenetic Response
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. José Eleuterio González
state: Nuevo Leon
Study officials:
References:
citation: Hochhaus A, Saussele S, Rosti G, Mahon FX, Janssen JJWM, Hjorth-Hansen H, Richter J, Buske C; ESMO Guidelines Committee. Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017 Jul 1;28(suppl_4):iv41-iv51. doi: 10.1093/annonc/mdx219. No abstract available.
citation: Johnson FM, Agrawal S, Burris H, Rosen L, Dhillon N, Hong D, Blackwood-Chirchir A, Luo FR, Sy O, Kaul S, Chiappori AA. Phase 1 pharmacokinetic and drug-interaction study of dasatinib in patients with advanced solid tumors. Cancer. 2010 Mar 15;116(6):1582-91. doi: 10.1002/cncr.24927.
citation: Naqvi K, Jabbour E, Skinner J, Anderson K, Dellasala S, Yilmaz M, Ferrajoli A, Bose P, Thompson P, Alvarado Y, Jain N, Takahashi K, Burger J, Estrov Z, Borthakur G, Pemmaraju N, Paul S, Cortes J, Kantarjian HM. Long-term follow-up of lower dose dasatinib (50 mg daily) as frontline therapy in newly diagnosed chronic-phase chronic myeloid leukemia. Cancer. 2020 Jan 1;126(1):67-75. doi: 10.1002/cncr.32504. Epub 2019 Sep 25.