Phase II trial of dasatinib in patients with Chronic Myeloid Leukemia in Chronic Phase after prior imatinib treatment.

• Conditions: Chronic Myeloid Leukemia in Chronic Phase; MedDRA version: 14.1Level: LLTClassification code 10054352Term: Chronic phase chronic myeloid leukemiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-004259-36-ES
• Lead Sponsor: Fundación PETHEMA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-11-12
• Last Update Posted: 4 February 2013

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1Adult patients >or = 18 years
2Diagnostic of Ph+ Chronic Myeloid Leukemia in first chronic phase
3Treated with Imatinib 400 mg per day or 600 mg per day for at least 18 months. A wash out period of at least 7 days for imatinib is required prior to dasatinib administration
4Patients meet criteria of late suboptimal response (complete cytogenetic response with no major molecular response) or have lost major molecular response
5Ability to understand and voluntarily sign the informed consent form
6Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy and have a negative pregnancy test, a maximum of 72 hours prior to study drug start. Sexually active men must also use effective contraceptive methods during the treatment.
7Women must not be breastfeeding.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 65
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 65

Exclusion Criteria

1.Patients treated with Imatinib at a dose different of 400/600 mg per day

2.Patients treated with other TKI than imatinib

3.Loss of cytogenetic response at study entry

4.ECOG ? 3

5.Inadequate bone marrow reserve: ANC <1.5 x 109/L and/or Platelet count < 100 x 109/L

6.Inadequate hepatic function (Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)> 2.5 X institutional upper limit of normal (IULN). Total bilirubin > 1.5 X IULN (unless Gilbert syndrome has been diagnosed)

7.Inadequate renal function (serum Cr >3 UNL or ClCr <45 ml/min)

8.Patients receiving concurrent treatment with other experimental drugs or anti-cancer therapy

9.Patients with uncontrolled concurrent disease:
a) Known pleural effusion at baseline
b) Clinically-significant gastrointestinal disease or surgery that would compromise absorption of study drug (eg, uncontrolled nausea or malabsorption syndrome)
c) Clinically-significant known coagulation or platelet function disorder (not related to thrombocytopenia), eg, von Willebrand?s disease
d) Other active malignancy requiring concurrent intervention
e) Uncontrolled or significant cardiovascular disease, including any of the following:
- Myocardial infarction within 6 months of enrolment date
- Uncontrolled angina or congestive heart failure within 3 months of enrolment date
- Left ventricular ejection fraction (LVEF) < 40%
- Significant cardiac conduction abnormality, including history of clinically-significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointe), history of third degree heart block or diagnosed congenital long QT syndrome, and/or prolonged QTc/f interval > 450 msec on baseline ECG.

10.Patients with active or uncontrolled infections or with serious illnesses or medical conditions that would not permit the patient to be managed according to the protocol.

11.Patients unable or unwilling to give written, informed consent prior to study participation.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of dasatinib in terms of major molecular response rate at 6 months in patients with CP-CML who have achieved complete cytogenetic response without major molecular response after at least 18 months on Imatinib 400/600.;Secondary Objective: ?To assess the efficacy of dasatinib in terms of depth and kinetics of molecular response.<br>?To assess the relationship of dasatinib with the appearance of large granular lymphocytes and assess the relationship of LGL with efficacy and toxicity.<br>?PFS;Primary end point(s): The primary efficacy endpoint is the Major molecular response rate at 6 months of dasatinib treatment.;Timepoint(s) of evaluation of this end point: At 6 months of dasatinib treatment.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The secondary efficacy endpoints include Major molecular response rate at 12 months, Complete molecular response rate at 6 and 12 moths, Incidence of lymphocytosis, Major and complete molecular response rates in patients with and without lymphocytosis and PFS.;Timepoint(s) of evaluation of this end point: At 6 and 12 months of dasatinib treatment.