Clinical Trials /

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

NCT03625388

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)

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
DasatinibElpida®Dasatinib 50 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

NameTypeDescriptionInterventions
Dasatinib 50 mgOtherDasatinib 50 mg orally once daily
  • Dasatinib
Dasatinib 100 mgOtherDasatinib 100 mg orally once daily
  • Dasatinib

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:Not yet 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

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