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

Chronic Myeloid Leukemia, Chronic Phase Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05638763
• Other study ID #: HE22-00031
• Status: Recruiting
• Phase: Phase 2
• Start date: November 2024
• Est. completion date: November 2024

Study information

• Verified date: November 2022
• Source: Hospital Universitario Dr. Jose E. Gonzalez
• Contact: Fernando De la Garza Salazar, MD
• Phone: (52) 811 080 2131
• Email: fernandodelagarza[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: November 2024
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia, Chronic Phase
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

Intervention

Drug:
• Dasatinib Pill
Patients will receive half pill of dasatinib 50mg (25mg/day, orally) for one year
• Ketoconazole Pill
Patients will receive ketoconazole 200mg two times a day, orally, for one year.

Locations

Country	Name	City	State
Mexico	Hospital Universitario Dr. José Eleuterio González	Monterrey	Nuevo Leon

Sponsors (2)

Lead Sponsor	Collaborator
Hospital Universitario Dr. Jose E. Gonzalez	Fernando De la Garza Salazar

Country where clinical trial is conducted

Mexico, 

References & Publications (3)

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. Erratum In: Ann Oncol. 2018 Oct 1;29(Suppl 4):iv261. — View 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. — View 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. — View Citation

Outcome

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