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

NCT ID: NCT05638763

Last Updated: 2022-12-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-30

Study Completion Date

2024-11-30

Brief Summary

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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

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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.

Conditions

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Chronic Myeloid Leukemia, Chronic Phase

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Dasatinib Pill

Intervention Type DRUG

Patients will receive half pill of dasatinib 50mg (25mg/day, orally) for one year

Ketoconazole Pill

Intervention Type DRUG

Patients will receive ketoconazole 200mg two times a day, orally, for one year.

Interventions

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Dasatinib Pill

Patients will receive half pill of dasatinib 50mg (25mg/day, orally) for one year

Intervention Type DRUG

Ketoconazole Pill

Patients will receive ketoconazole 200mg two times a day, orally, for one year.

Intervention Type DRUG

Other Intervention Names

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Sprycel Nizoral

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fernando De la Garza Salazar

UNKNOWN

Sponsor Role collaborator

Hospital Universitario Dr. Jose E. Gonzalez

OTHER

Sponsor Role lead

Responsible Party

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David Gomez Almaguer

Head of Department

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Hospital Universitario Dr. José Eleuterio González

Monterrey, Nuevo León, Mexico

Site Status RECRUITING

Countries

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Mexico

Central Contacts

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Fernando De la Garza Salazar, MD

Role: CONTACT

(52) 811 080 2131

Facility Contacts

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Dr Fernando De la Garza Salazar, MD

Role: primary

8442322102

Fernando De la Garza Salazar, MD

Role: backup

8442322102

References

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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.

Reference Type BACKGROUND
PMID: 28881915 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20108303 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31553487 (View on PubMed)

Other Identifiers

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HE22-00031

Identifier Type: -

Identifier Source: org_study_id

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