Description:
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)
Title
- Brief Title: Low Dose Dasatinib (50 mg Daily) as First-line Treatment for Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia
- Official Title: Randomized, Open-Label, Phase II, Multicenter, Multi-Country Study to Evaluate Safety and Efficacy of Dasatinib 50 mg in First-Line Treatment of Early Chronic Phase Chronic Myeloid Leukemia
Clinical Trial IDs
- ORG STUDY ID:
LPI-JOR-LEB-KSA-TUN-2017-01
- NCT ID:
NCT03625388
Conditions
- Chronic Myelogenous Leukemia
Interventions
Drug | Synonyms | Arms |
---|
Dasatinib | Elpida® | Dasatinib 100 mg |
Purpose
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)
Detailed Description
A multicenter, prospective, open-label, randomized Phase II study to compare efficacy by
measuring rates of major molecular response (MMR) at 12 months in patients with Ph+ chronic
phase (CP) chronic myeloid leukemia (CML) randomized to receive either dasatinib 50 mg QD or
dasatinib 100 mg QD. Approximately 100 patients are expected to be randomized. The duration
of patient participation will be 18 months
Trial Arms
Name | Type | Description | Interventions |
---|
Dasatinib 50 mg | Other | Dasatinib 50 mg orally once daily | |
Dasatinib 100 mg | Other | Dasatinib 100 mg orally once daily | |
Eligibility Criteria
Inclusion Criteria:
1. Age ≥ 18 years.
2. 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).
3. 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.
4. ECOG performance of 0-2.
5. 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.
6. 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
Exclusion Criteria:
1. NYHA cardiac class 3-4 heart disease
2. Cardiac symptoms - Patients meeting the following criteria are not eligible unless
cleared by a cardiologist:
1. Uncontrolled angina within 3 months
2. Diagnosed or suspected congenital long QT syndrome
3. Any history of clinically significant ventricular arrhythmias (such as
ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
4. Prolonged QTc interval on pre-entry electrocardiogram (>460 msec)
3. History of significant bleeding disorder unrelated to cancer including:
1. Diagnosed congenital bleeding disorders (e.g. Von Willebrand's disease)
2. Diagnosed acquired bleeding disorder within one year (e.g. acquired anti-factor
VIII antibodies)
3. Isolated thrombocytopenia without recurrent bleeding episodes shall be considered
eligible for study entry
4. Patients with active uncontrolled psychiatric disorders including: psychosis, major
depression, and bipolar disorders
5. 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
1. 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
2. Postmenopausal women must be amenorrheic for at least 12 months to be considered
of non-childbearing potential
3. Women must continue birth control for the duration of the study and at least 3
months after the last dose of study drug
6. Pregnant or breast-feeding women are excluded
a. All WOCBP must have a negative pregnancy test prior to first receiving the study
drug. If the pregnancy test is positive, the patient must not receive the study drug
and must not be enrolled in the study.
7. Patients in late chronic phase (i.e. time from diagnosis to treatment >12 months),
accelerated phase (except as noted in inclusion criteria 2) or blast phase are
excluded.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Proportion of patients who achieve and maintain MMR at 12 months using RQ-PCR test |
Time Frame: | 12 months |
Safety Issue: | |
Description: | Major molecular response (MMR) is defined as BCR-ABL1 ≤ 0.1% |
Secondary Outcome Measures
Measure: | Incidence of adverse events (AEs) and serious adverse events (SAEs) to dasatinib |
Time Frame: | 18 months |
Safety Issue: | |
Description: | Evaluation of adverse events (AEs), serious AEs (SAEs), and clinically relevant changes in laboratory tests according to laboratory reference ranges |
Measure: | Transformation free survival (TFS) in eligible patients randomized to dasatinib 50 mg or dasatinib 100 mg treatment arms |
Time Frame: | 18 months |
Safety Issue: | |
Description: | Transformation free survival was measured from the start of therapy to the date of transformation to accelerated or blastic phases while on therapy or to the date of last follow-up. |
Measure: | Event free survival (EFS) |
Time Frame: | 18 months |
Safety Issue: | |
Description: | EFS is measured from the start of treatment to the date of any of the following events : loss of CHR, loss of CCyR or MCyR, dose escalation, discontinuation of therapy for toxicity or lack of efficacy, progression to AP or BP, or death from any cause at any time |
Measure: | Blastic phase (BP) transformation |
Time Frame: | 18 months |
Safety Issue: | |
Description: | BP is defined as the presence of 30% blasts or more in the peripheral blood or bone marrow |
Measure: | Overall survival |
Time Frame: | 18 months |
Safety Issue: | |
Description: | Overall survival time is defined as the time from date of randomization until the date of death from any cause at any time or date of last follow up |
Measure: | Proportion of patients with Complete cytogenetic response (CCyR) at 12 months |
Time Frame: | 12 months |
Safety Issue: | |
Description: | defined as 0% Ph+ metaphases, or FISH ≤2%, or BCR-ABL transcripts (IS) ≤1% |
Measure: | Proportion of patients with MR 4.5 at 18 months |
Time Frame: | 18 months |
Safety Issue: | |
Description: | (BCR-ABL transcripts ≤ 0.0032%) |
Measure: | Health-Related Quality of Life (HRQoL): EORTC QOLCML24 |
Time Frame: | 18 months |
Safety Issue: | |
Description: | Mean change in Health-Related Quality of Life (HRQoL) utilizing EORTC QOLCML24 questionnaire throughout treatment visits |
Measure: | Frequency of not taking the medications as prescribed |
Time Frame: | 18 months |
Safety Issue: | |
Description: | Evaluated by identifying the frequency of not taking the medications as prescribed and the reasons. The decision on non-compliance is based on the treating physician's judgment. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Hikma Pharmaceuticals LLC |
Trial Keywords
- Leukemia, Myeloid, Philadelphia Positive
- Dasatinib
- Generic Dasatinib
- Dasatinib 50 mg once daily
- Early chronic phase chronic myeloid leukemia
Last Updated
March 4, 2020