Open label study with Dasatinib in patients with Chronic Phase Chronic Myeloid Leukemia treated with Imatinib

Phase 1

Conditions: Chronic Phase Chronic Myeloid Leukemia
MedDRA version: 20.0Level: LLTClassification code 10054352Term: Chronic phase chronic myeloid leukemiaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Registration Number: EUCTR2011-006181-41-AT

Lead Sponsor: Bristol-Myers Squibb International Corporation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 258

Inclusion Criteria

1.CML-CP patients with CHR but with BCR-ABL level > 10% IS after 3 months of imatinib 400 mg treatment. Imatinib monotherapy should have been started within 6 months of CP-CML diagnosis.
2.Men and women with CML-CP Ph+ > age 18
3.Currently tolerating imatinib 400 mg QD
4.ECOG performance status = 0 – 2
5.Patient willing and able to give informed consent
6.Life expectancy >6 months
7.Adequate renal function defined as serum creatinine = 3 times the institutional ULN.
8.Adequate hepatic function defined as: total bilirubin = 2.0 times the institutional ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 times the institutional upper limit of normal (ULN).
9.Serum Na, K, Mg, and total serum Ca or ionized Ca levels must be greater than or equal to the institutional lower limit of normal. Subjects with low K, Mg levels, total serum Ca and/or ionized Ca must be replete to allow for protocol entry.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 129
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 129

Exclusion Criteria

1.Patients who are pregnant or breastfeeding or likely to become pregnant.
2.Men whose partner is unwilling or unable to avoid pregnancy
3.Prior or concurrent malignancy, except for the following:
a.Curatively treated basal cell or squamous cell skin cancer
b.Cervical carcinoma in situ
c.Adequately treated Stage I or II cancer from which the subject is currently in complete remission
d.Any other cancer from which the subject has been disease free for 3 years
4.Documented T315I7A, F317L or V299L mutations (if already available – not required for screening)
5.Medical History and concurrent medical conditions, including:
a.A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy
b.Uncontrolled or significant cardiovascular disease, including any of the following:
i.Congestive cardiac failure (NYHA >2) within 3 months
ii.Diagnosed or suspected congenital long QT syndrome
iii.Any history of clinically significant ventricular arrhythmias
iv.Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec)
v.Any history of second or third degree heart block (may be eligible if the subject currently has a pacemaker)
vi.Uncontrolled angina within 3 months
vii.Prior myocardial infarction within 6 months
viii.Uncontrolled hypertension
c.Pulmonary arterial hypertension
d.Pleural or pericardial effusions of any grade at randomisation are excluded. Subjects previously diagnosed with pleural/pericardial effusion of any grade resolved at the time of randomisation are allowed.
e.History of significant bleeding disorder unrelated to CML, including
i.Diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease)
ii.Diagnosed acquire bleeding disorder within on e year (e.g., acquired anti-factor VIII antibodies)
f.Prior chemotherapy for peripheral stem cell mobilization. (Prior collection of unmobilized peripheral blood stem cells is permitted).
g.Previous diagnosis of accelerated phase or blast crisis
h.Subjects with clonal evolution in Ph+ cells observed in = 2 metaphases at baseline bone marrow cytogenetic test, unless the same abnormalities were present at diagnosis. Patients with no evidence of clonal evolution, including those patients whose cytogenetic testing fails or bone marrow aspiration is a dry tap tap at 3 months, are elegible for the study.
i.Subjects with less than Complete Hematologic Response (CHR) after 3 months of imatinib treatment or lost CHR after initial achievement.
j.Subjects intolerant to Imatinib 400 mg QD prior to enrolment.
l. Subjects with known hypersensitivity to excipients of dasatinib
lactose monohydrate, microcrystalline cellulose, croscarmellose sodium;
hydroxypropyl cellulose, magnesium stearate; Film 400).
6. Prohibited treatments and/or other treatments
a.History of TKI exposure within the previous 12 months apart from imatinib
b.Subject with any anti-CML other than imatinib (except HU or anagralide)
7.Subjects with prior stem cell transplantation and/or high dose chemotherapy for CML
8.Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study.
Rescreening is permitted in the event of temporary biochemical abnormalities

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: To compare the following between both arms:<br>otime to MMR<br>otime to MR4.5<br>oProgression Free Survival (PFS)<br>oOverall Survival (OS) <br>;Primary end point(s): The primary endpoint for this study is the proportion of randomized subjects who achieve<br>MMR at 12 months after the first day (Day 1) treatment with first-line imatinib in<br>patients in each treatment group;Timepoint(s) of evaluation of this end point: 12 months after day 1 imatinib treatment;Main Objective: To compare the rate of major molecular response (MMR) at 12 months after Day 1initiation of first line treatment with imatinib, in patients randomized at month 3 to treatment with dasatinib 100mg QD or imatinib at any dose, after less than optimal response to 1st line imatinib

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Time to MMR, MR4.5, PFS, OS ;Timepoint(s) of evaluation of this end point: at month 6, 12, 15, 18, 24, 36, 48, after day 1 of imatinib therapy

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