Low Dose Dasatinib (50 mg Daily) as First-line Treatment for Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia

NCT03625388 | Completed Phase 2

• 1 other identifier: LPI-JOR-LEB-KSA-TUN-2017-01
• Study Type: interventional
• Target: 56
• Locations: 4 countries
• Sites: 5

Brief Summary

The purpose of this multicenter randomized study is to compare efficacy and safety of dasatinib 50 mg once daily and dasatinib 100 mg once daily in patients with early chronic phase (CP) chronic myeloid leukemia (CML)

Conditions

Chronic Myelogenous Leukemia

Keywords

Leukemia, Myeloid, Philadelphia Positive; Dasatinib; Generic Dasatinib; Dasatinib 50 mg once daily; Early chronic phase chronic myeloid leukemia

Outcome Measures

Primary Outcomes (1)

• Proportion of patients who achieve and maintain MMR at 12 months using RQ-PCR test

  Major molecular response (MMR) is defined as BCR-ABL1 ≤ 0.1%

  12 months

Secondary Outcomes (9)

• Incidence of adverse events (AEs) and serious adverse events (SAEs) to dasatinib

  18 months

• Transformation free survival (TFS) in eligible patients randomized to dasatinib 50 mg or dasatinib 100 mg treatment arms

  18 months

• Event free survival (EFS)

  18 months

• Blastic phase (BP) transformation

  18 months

• Overall survival

  18 months

Study Arms (2)

Dasatinib 50 mg

OTHER

Dasatinib 50 mg orally once daily

Drug: Dasatinib

Dasatinib 100 mg

OTHER

Dasatinib 100 mg orally once daily

Drug: Dasatinib

Interventions

Dasatinib DRUG

Film coated tablet contains dasatinib monohydrate

Also known as: Elpida®

Dasatinib 100 mg; Dasatinib 50 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Diagnosis of Ph+ or BCR-ABL positive CML in early CP (i.e. time from diagnosis \<12 months). Except for hydroxyurea and/or 1-2 doses of cytarabine (up to 6g/m2 total), patients must have received no or minimal prior therapy, defined as 30 days of prior approved tyrosine kinase inhibitor (TKI).
• Clonal evolution defined as the presence of additional chromosomal abnormalities other than the Ph-chromosome has been historically included as a criterion of accelerated phase (AP). However, patients with clonal evolution as the only criterion of AP have a significantly better prognosis, and when present at diagnosis may not impact the prognosis at all. Thus, patients with clonal evolution and no other criteria for AP will be eligible for this study.
• ECOG performance of 0-2.
• Adequate end organ function defined as the following: total bilirubin \<1.5x ULN (unless secondary to Gilbert's disease, in which case it should be \<2.5x ULN), SGPT \<2.5x ULN, creatinine \<1.5x ULN.
• Patients must sign an informed consent form (ICF) indicating they are aware of the investigational nature of this study, in keeping with the policies of the hospital

You may not qualify if:

• NYHA cardiac class 3-4 heart disease
• Cardiac symptoms - Patients meeting the following criteria are not eligible unless cleared by a cardiologist:
• Uncontrolled angina within 3 months
• Diagnosed or suspected congenital long QT syndrome
• Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
• Prolonged QTc interval on pre-entry electrocardiogram (\>460 msec)
• History of significant bleeding disorder unrelated to cancer including:
• Diagnosed congenital bleeding disorders (e.g. Von Willebrand's disease)
• Diagnosed acquired bleeding disorder within one year (e.g. acquired anti-factor VIII antibodies)
• Isolated thrombocytopenia without recurrent bleeding episodes shall be considered eligible for study entry
• Patients with active uncontrolled psychiatric disorders including: psychosis, major depression, and bipolar disorders
• Women of pregnancy potential must practice an effective method of birth control, unless otherwise instructed, during the course of the study in a manner such that risk of failure is minimized
• Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during study participation and the potential risk factors for an unintentional pregnancy
• Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential
• Women must continue birth control for the duration of the study and at least 3 months after the last dose of study drug

Sponsors & Collaborators

• Hikma Pharmaceuticals LLC: lead

Study Sites (5)

King Hussein Cancer Center (KHCC)

Amman, 11941, Jordan

Location

Jordan University Hospital (JUH)

Amman, 11942, Jordan

Location

American University of Beirut Medical Center (AUBMC)

Beirut, Lebanon

Location

The King Faisal Specialist Hospital and Research Centre (KFSH&RC)

Riyadh, Saudi Arabia

Location

Aziza Othmana Hospital

Tunis, 1006, Tunisia

Location

MeSH Terms

Conditions

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

Interventions

Dasatinib; elsulfavirine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Eligible patients will be randomized to receive either dasatinib 50 mg or dasatinib 100 mg orally once daily for the duration of the study which is 18 months.

Study Record Dates

• First Submitted: August 2, 2018
• First Posted: August 10, 2018
• Study Start: November 5, 2018
• Primary Completion: July 22, 2023
• Study Completion: July 22, 2023
• Last Updated: September 22, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

JO (2); LE (1); SA (1); TU (1)