E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
pacientes con leucemia linfocítica crónica de células B |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003892 |
E.1.2 | Term | B-cell chronic lymphocytic leukaemia/prolymphocytic leukaemia/small lymphocytic lymphoma |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate the safety and tolerability of acadesine in patients with B-CLL. |
|
E.2.2 | Secondary objectives of the trial |
To determine the pharmacokinetics of acadesine and its metabolite, ZMP. To determine the optimal biological dose of acadesine in patients with B-CLL.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
|
|
E.4 | Principal 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: o Significant cardiac disease - New York Heart Association Classes III or IV or have suffered a myocardial infarction in the last 6 months. o Chronic pulmonary obstructive disease with hypoxemia. o Clinically active auto-immune disease. o Active 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.
|
|
E.5 End points |
E.5.1 | 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. • Pharmacokinetics: pharmacokinetic profile of acadesine in plasma and its metabolite, ZMP, in whole blood. • Pharmacodynamics: the effects of acadesine on B-cell and T-cell counts in peripheral blood.
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
first administration to humans with B-CLL, acadesine has been used in humans for other indications |
|
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
For administrative and safety reporting purposes the end of the study will be defined as the date of the clinical database lock.
The clinical database will be locked after information from the last patient's last study visit has been recorded to ensure all patient safety information is included in the database. The sponsor will ensure that the concerned CAs are notified of the end of trial within 90 days of the last visit of the last patient undergoing the trial. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |