CLL patients with thrombocytopenia and indication for chemotherapeutic treatment with alkylating agents and/or purine analogues MedDRA version: 15.1 Level: LLT Classification code 10008977 Term: Chronic lymphocytic leukemia recurrent System Organ Class: 100000004864 MedDRA version: 15.1 Level: LLT Classification code 10068919 Term: B-cell chronic lymphocytic leukemia System Organ Class: 100000004864
Conditions
Sponsors
Universitätsklinikum Ulm
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Confirmed diagnosis of CLL (based on immunophenotyping performed at the central reference laboratory of the GCLLSG in Cologne) •Platelet count =65 years) yes F.1.3.1 Number of subjects for this age range 41
Exclusion criteria
Exclusion criteria: •Thrombocytopenia that is primarily caused by ITP •Refractory CLL: defined as treatment failure (failure to achieve a CR or PR) or disease progression within 6 months of last anti-leukemic therapy , including fludarabine and/or bendamustine. NOTE: Subjects refractory to rituximab monotherapy as last therapy are permitted •No prior therapy for CLL •Active autoimmune hemolytic anemia (AIHA) requiring corticosteroid therapy >100mg equivalent to hydrocortisone, or chemotherapy •Platelet count > 50 000/µl at screening •Richter’s transformation •CNS involvement of B-CLL •Active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment •Past or current malignancy other than CLL (with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix or breast) unless tumor was successfully treated with curative intent at least 2 years prior to trial entry •Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months, congestive heart failure, etc. •History of significant cerebrovascular disease •Recurring venous thrombosis or pulmonary embolism •Glucocorticoids unless given in doses = 100 mg/day hydrocortisone (or equivalent dose of other glucocorticoids) and for exacerbations other than CLL (e.g. asthma) •Known HIV positivity •Active hepatitis B, C •Treatment with an investigational drug within 30 days or five half-lives (whichever is longer) preceding the first dose of eltrombopag. •Subjects known or suspected of not being able to comply with a study protocol •Patients with recent history of arterial or venous thrombosis (stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis or pulmonary embolism) within the preceding 6 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: •Safety and tolerability of eltrombopag by evaluating adverse events and changes from baseline in vital signs and clinical laboratory parameters (compared to placebo, phase II) •To evaluate the incidence and durability of platelet response (compared to placebo, phase II) •To determine the incidence and severity of bleeding events (WHO bleeding scale, compared to placebo, phase II) •To analyze the pharmacokinetics and the relationship between pharmacokinetics and pharmacodynamics of eltrombopag and platelet counts (compared to placebo, phase II) •To determine the effect of eltrombopag on the use of platelet transfusion(s) to treat thrombocytopenia (compared to placebo, phase II) •To evaluate chemotherapy dose delay/dose reduction in eltrombopag groups compared to placebo (phase II) •To examine the eltrombopag effect in relation to data on the cause of thrombocytopenia •CLL overall response rate & time to progression •To evaluate trough-level pharmacokinetics of eltrombopag;Primary end point(s): Phase I: dose-escalation trial (4 doses of eltrombopag: 75mg, 150mg, 225mg, 300mg) to find an appropriate, feasible dose to achieve an increase in platelet count from <50.000/µ to =100.000/µl. An empirical, two-step escalation design with 3 to 6 patients on each dose level is used. Phase II: the platelet stimulation efficacy of the determined dose level will be estimated. Platelet responders are defined as achieving platelet counts =100.000/µl prior to cycle 1 of chemotherapy and platelet counts =75.000/µl in the subsequent 3 cycles (or 3 month in case of continuous chemotherapy). ;Timepoint(s) of evaluation of this end point: Phase I: for the decision on a definite MTD at least 6 patients have to be treated on the respective dose level for 2 weeks, with a maximum of one case of dose limiting toxicity. In case of toxicity in 2 cases or more, the next lower dose is declared as MTD (or the trial terminated completely if this happens on the first dose level | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Comparison of: •adverse event/toxicity rates •number of bleeding events according to WHO bleeding scale •rate of patients with chemotherapy dose delay/reduction •CLL overall best response rate •platelets nadir •durations of thrombocytopenia •number of platelet transfusions •progression-free survival of CLL disease •duration of platelet response •pharmacokinetical analyses ;Timepoint(s) of evaluation of this end point: End points of trial will be evaluated whenever they occur (adverse events) as well as at patient visits during and after study treatment (follow-up). | — |
Countries
Austria, Germany
Contacts
Public ContactClinical Trial Information
Deutsche CLL Studiengruppe (DCLLSG)
Outcome results
None listed