A Phase I/II Open-Label Dose Escalation Study to Investigate the Safety and Tolerability of Acadesine in Patients with B-Cell Chronic Lymphocytic Leukaemia

Conditions: Patients with B-Cell Chronic Lymphocytic Leukemia
MedDRA version: 9.1Level: LLTClassification code 10003892Term: B-cell chronic lymphocytic leukaemia/prolymphocytic leukaemia/small lymphocytic lymphoma

Registration Number: EUCTR2007-002557-23-FR

Lead Sponsor: Protherics Medicines Development Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 40

Inclusion Criteria

•B-CLL patients with refractory or relapsed disease who have received either a fludarabine containing treatment regimen or an alkylating agent.
•Diagnosis of B-CLL according to NCI Working Group Criteria.
•Have an elevated B-cell count of = 5000/mm3.
•Have a T-cell count = 200/mm3.
•ECOG Performance Status < 2.
•Have a life expectancy of at least 3 months.
•Age > 18 years, of either gender.
•Have given written informed consent, prior to any study related procedure not part of the patient’s normal medical care.

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•Patients who, in the opinion of the Investigator, need immediate treatment with proven chemotherapy and/or immunotherapy, and/or transplantation.
•Have B-CLL with central nervous system involvement.
•Have participated in any other investigational drug study or have undergone an experimental therapeutic procedure considered to potentially interfere with the study in the 30 days preceding Day 1.
•Have received chemotherapy or radiotherapy treatment in the 30 days preceding Day 1.
•Require use of drugs or substances which inhibit platelet aggregation during the 30 days prior to Day 1 or during the study. These include: ADP receptor inhibitors (ticlopidine, clopidogrel), aspirin and other NSAIDs including COX inhibitors (except COX-2-selective inhibitors), dipyridamole, phosphodiesterase inhibitors (cilostazol), calcium channel blockers such as nifedipine, xanthines (eg theophylline, aminophylline) and substances containing caffeine. Glycoprotein IIB/IIIA inhibitors, including abciximab, eptifibatide and tirofiban, are also contraindicated.
•Require oral or parenteral steroids with the exception of inhaled steroids or low-dose oral steroids (<10mg prednisolone per day or equivalent) for an indication other than B-CLL.
•Have a serious medical or psychiatric condition that could, in the Investigator’s opinion, potentially interfere with their treatment and/or participation in the study.
•Have uncontrolled diabetes mellitus that requires insulin treatment or is not controlled on oral therapy.
•Have a history of gout.
•Have a serious concomitant disease including:
oSignificant cardiac disease - New York Heart Association Classes III or IV or have suffered a myocardial infarction in the last 6 months.
oChronic pulmonary obstructive disease with hypoxemia.
oClinically active auto-immune disease.
oActive infection such as tuberculosis, CMV (Cytomegalovirus).
•Any secondary malignancy requiring active treatment (except hormonal therapy).
•Have inadequate bone marrow reserve: neutrophils < 1.0 x 109/L, platelet count < 50 x 109/L (unsupported by transfusion), or coagulation abnormalities.
•Have inadequate liver function: total bilirubin > 1.5 x upper limit of normal values (ULN), AST, ALT, or alkaline phosphatase > 2.5 x ULN.
•Have inadequate renal function, defined by serum creatinine = 1.5 x ULN, unless creatinine clearance is measured and found to be at least 90 mL/min.
•Have serum uric acid levels outside the normal range.
•Females of childbearing potential who are unwilling to employ adequate means of contraception (hormonal contraceptive, intrauterine device, diaphragm with spermicide or condom with spermicide) for the duration of the study and 30 days after the last acadesine administration.
•Pregnant or lactating females.
•Male patients who are not surgically sterile and who are unwilling to use a condom with spermicide for the duration of the study and for 3 months after the last acadesine administration.
•Abuse of alcohol or other recreational drugs.
•Known HIV or Hepatitis B (unless clearly due to vaccination) or C positive.
•Known allergy to acadesine or any of its excipients.
•Have undergone previous allogeneic stem cell transplant.
•Transformation to Richter’s syndrome or other aggressive B-cell malignancy.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary end point(s): •Safety and tolerability: adverse events and serious adverse events (incidence, causality, severity), local tolerability, changes in laboratory values (including liver enzymes, blood glucose and uric acid) and vital signs. Adverse events will be assessed for their relationship to acadesine and classified for severity according to the NCI CTCAE v3.0.<br>•Pharmacokinetics: pharmacokinetic profile of acadesine in plasma and its metabolite, ZMP, in whole blood. <br>•Pharmacodynamics: the effects of acadesine on B-cell and T-cell counts in peripheral blood.<br>;Main Objective: To demonstrate the safety and tolerability of acadesine in patients with B-CLL. ;Secondary Objective: To determine the pharmacokinetics of acadesine and its metabolite, ZMP.<br>To determine the optimal biological dose of acadesine in patients with B-CLL.<br>

Secondary Outcome Measures

Name	Time	Method

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