Dasatinib treatment combination for fludarabine-refractory Chronic Lymphocytic Leukemia (CLL)

Phase 2

Not yet recruiting

Conditions: chronic lymphocytic leukenia
B cell leukemia
10024324

Registration Number: NL-OMON37297

Lead Sponsor: AMC afdeling hematologie

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 35

Inclusion Criteria

- CLL confirmed according to the IWCLL Working Group criteria;
- Binet stages A or B with indication for treatment according to IWCLL guidelines, or Binet C AND
- Fludarabine refractory, defined as relapse within 6 months following fludarabine containing chemo(immuno)therapy;
- Age 18-80 years inclusive;
- WHO performance status * 2;

Exclusion Criteria

- Richter*s transformation;
- Suspected or documented CNS involvement by CLL;
- Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure, symptomatic ischemic heart disease or prolonged QT interval);
- Severe pulmonary dysfunction (CTCAE grade III-IV);
- Severe neurological or psychiatric disease;
- Significant hepatic dysfunction (serum bilirubin or transaminases * 3 times normal level) except when caused by leukemic infiltration;
- Significant renal dysfunction (creatinine clearance < 30 ml/min after rehydration);
- History of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma;
- Concurrent use of CYP3A4 inducers or inhibitors, or QTc-prolonging agents;
- Active, uncontrolled infections;
- Female patients of reproductive potential who are not using effective contraception;

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Clinical response rate and quality ( CR, PR) at 28 weeks according to the<br /><br>IWCLL Working Group criteria<br /><br>In case of complete responses: minimal residual disease status as assessed by<br /><br>flow cytometry</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Overall safety profile as determined by the incidence of clinically significant<br /><br>adverse events.<br /><br>Event free survival (i.e. time from registration to induction failure,<br /><br>progression, relapse or death whichever occurs first), progression free<br /><br>survival (i.e. time from registration to disease progression, relapse or death<br /><br>due to CLL whichever occurs first) and disease free survival (i.e. time from CR<br /><br>to relapse)<br /><br><br /><br>Extensive (functional) In vitro studies of dasatinib treated cells will be<br /><br>performed:<br /><br>- Expression profile of apoptosis regulatory genes at the mRNA level (MLPA) and<br /><br>protein level (western blot),<br /><br>- Study in vitro synergy of dasatinib treatment with different chemotherapeutic<br /><br>and immunotherapeutic drugs.</p><br>