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

Primary Purpose

Chronic Myeloid Leukemia, Chronic Phase

Status

Recruiting

Phase

Phase 2

Locations

Mexico

Study Type

Interventional

Intervention

Dasatinib Pill

Ketoconazole Pill

About this trial

This is an interventional treatment trial for Chronic Myeloid Leukemia, Chronic Phase

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age >18 years Chronic myeloid leukemia in chronic phase according to the World Health Organization 2016 Eastern Cooperative Oncology Group (ECOG) 0-2 Exclusion Criteria: Chronic heart disease (NYHA III-IV) Bleeding disorders not attributed to the hematological malignancy Pregnancy Lactation Chronic myeloid leukemia in blast phase Organic dysfunction (Marshall score ≥2)

Sites / Locations

Hospital Universitario Dr. José Eleuterio GonzálezRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dasatinib and ketoconazole

Arm Description

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.

Outcomes

Primary Outcome Measures

The rate of Complete Cytogenetic Response

B-cell antigen receptor(BCR)/Tyrosine-protein kinase-ABL1(ABL1) IS <=1% at 6 months

Secondary Outcome Measures

The rate of Molecular Response (MR4)

Log reduction in BCR/ABL of 4

The rate of Molecular Response (MR4.5)

Log reduction in BCR/ABL of 4.5

The rate of sustained Molecular Response (MR4.5)

Log reduction in BCR/ABL of 4.5

The proportion of non hematological side effects

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

The rate of Complete Cytogenetic Response

BCR/ABL IS <=1% at 12 months

Full Information

NCT ID

NCT05638763

First Posted

November 16, 2022

Last Updated

November 25, 2022

Sponsor

Hospital Universitario Dr. Jose E. Gonzalez

Collaborators

Fernando De la Garza Salazar

1. Study Identification

Unique Protocol Identification Number

NCT05638763

Brief Title

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

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Recruiting

Study Start Date

November 2024 (Anticipated)

Primary Completion Date

November 2024 (Anticipated)

Study Completion Date

November 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Hospital Universitario Dr. Jose E. Gonzalez

Collaborators

Fernando De la Garza Salazar

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Myeloid Leukemia, Chronic Phase

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Dasatinib and ketoconazole

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Dasatinib Pill

Other Intervention Name(s)

Sprycel

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Ketoconazole Pill

Other Intervention Name(s)

Nizoral

Intervention Description

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

Primary Outcome Measure Information:

Title

The rate of Complete Cytogenetic Response

Description

B-cell antigen receptor(BCR)/Tyrosine-protein kinase-ABL1(ABL1) IS <=1% at 6 months

Time Frame

Up to 6 months

Secondary Outcome Measure Information:

Title

The rate of Molecular Response (MR4)

Description

Log reduction in BCR/ABL of 4

Time Frame

Up to 6 months

Title

The rate of Molecular Response (MR4.5)

Description

Log reduction in BCR/ABL of 4.5

Time Frame

Up to 6 months

Title

The rate of sustained Molecular Response (MR4.5)

Description

Log reduction in BCR/ABL of 4.5

Time Frame

Up to 12 months

Title

The proportion of non hematological side effects

Description

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

Time Frame

Up to 12 months

Title

The rate of Complete Cytogenetic Response

Description

BCR/ABL IS <=1% at 12 months

Time Frame

Up to 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Fernando De la Garza Salazar, MD

Phone

(52) 811 080 2131

fernandodelagarza@gmail.com

Facility Information:

Facility Name

Hospital Universitario Dr. José Eleuterio González

City

Monterrey

State/Province

Nuevo Leon

ZIP/Postal Code

64630

Country

Mexico

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Dr Fernando De la Garza Salazar, MD

Phone

8442322102

fernandodelagarza@gmail.com

First Name & Middle Initial & Last Name & Degree

Fernando De la Garza Salazar, MD

Phone

8442322102

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

28881915

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

Results Reference

background

PubMed Identifier

20108303

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.

Results Reference

background

PubMed Identifier

31553487

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.

Results Reference

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

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