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

• Sponsor: Hospital Universitario Dr. Jose E. Gonzalez (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05638763
• Collaborator: Fernando De la Garza Salazar (Other)
• Enrollment: 15
• Location: 1
• Arm: 1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloid Leukemia, Chronic Phase	Drug: Dasatinib Pill; Drug: Ketoconazole Pill	Phase 2

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Cytochrome P450 Inhibition With Ketoconazole to Decrease Dosage and Costs of Dasatinib for Chronic Myelogenous Leukemia
• Anticipated Study Start Date: Nov 1, 2024
• Anticipated Primary Completion Date: Nov 1, 2024
• Anticipated Study Completion Date: Nov 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dasatinib and ketoconazole 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; Patients will receive half pill of dasatinib 50mg (25mg/day, orally) for one year; Other Names: Sprycel ; Drug: Ketoconazole Pill; Patients will receive ketoconazole 200mg two times a day, orally, for one year.; Other Names: Nizoral

Outcome Measures

Primary Outcome Measures

1. 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

1. The rate of Molecular Response (MR4) [Up to 6 months]

   Log reduction in BCR/ABL of 4

2. The rate of Molecular Response (MR4.5) [Up to 6 months]

   Log reduction in BCR/ABL of 4.5

3. The rate of sustained Molecular Response (MR4.5) [Up to 12 months]

   Log reduction in BCR/ABL of 4.5

4. The proportion of non hematological side effects [Up to 12 months]

   Proportion of patients that presented non hematological side effects to the intervention

5. The rate of Complete Cytogenetic Response [Up to 12 months]

   BCR/ABL IS <=1% at 12 months

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Universitario Dr. José Eleuterio González	Monterrey	Nuevo Leon	Mexico	64630

Sponsors and Collaborators

• Hospital Universitario Dr. Jose E. Gonzalez
• Fernando De la Garza Salazar

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.
• 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.

• Responsible Party: David Gomez Almaguer, Head of Department, Hospital Universitario Dr. Jose E. Gonzalez
• ClinicalTrials.gov Identifier: NCT05638763
• Other Study ID Numbers: HE22-00031
• First Posted: Dec 6, 2022
• Last Update Posted: Dec 6, 2022
• Last Verified: Nov 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Ketoconazole; Dasatinib

Study Results

No Results Posted as of Dec 6, 2022