E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10020206 |
E.1.2 | Term | Hodgkin's disease |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the anti-lymphoma efficacy of daily oral doses of ITF2357 folllowed by intravenous Mechlorethamine administered to patients with refractory/relapsed Hodgkins lymphoma |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of multiple courses of ITF2357 folllowed by Mechlorethamine in a population of chemotherapy pretreated patients |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Written Informed Consent. Age ≥18 years. Histologically confirmed diagnosis of Hodgkins lymphoma. Subjects who have failed second-line or subsequent-line salvage chemo-radiotherapy regimens for whom no other treatment options of proven efficacy can be given. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements - ANC ≥1500/µL; Platelet count ≥75000/µL - Hemoglobin ≥9 g/dL (may not be transfused or treated with erythropoietin to maintain or exceed this level) - Total bilirubin ≤1.6 mg/dL; AST or ALT ≤2.5 times the upper limit of normal - Serum creatinine ≤2.0 mg/dL or creatinine clearance >50 mL/min - Serum Potassium and Magnesium within normal limits Subjects with at least one bi-dimensional lesion measurable by CT-scan or MRI, according to the Revised Response Criteria for Malignant Lymphoma of the International Working Group (J Clin Oncol, 25:579-586, 2007). ECOG performance status of 0 or 1 Use of an effective means of contraception for women of childbearing potential and men with partners of childbearing potential Life expectancy of >3 months Subjects receiving intravenous Mechlorethamine (6 mg/sqm) as single agent at least 4 weeks before study entry |
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E.4 | Principal exclusion criteria |
Active bacterial or mycotic infection requiring antimicrobial treatment Pregnancy or lactation Anticancer chemotherapy or radiotherapy during the study or within 4 weeks of study entry. A marked baseline prolongation of QT/QTc interval (e.g. repeated demonstration of a QTc interval > 450 ms, according to Bazetts correction formula see appendix I for the formula) Use of concomitant medications that prolong the QT/QTc interval (see appendix H for full list) Clinically significant cardiovascular disease including: - Uncontrolled hypertension, myocardial infarction, unstable angina - New York Heart Association (NYHA) Grade II or greater congestive heart failure - History of any cardiac arrhythmia requiring medication (irrespective of its severity) - A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) Positive blood test for HIV, HBV and HCV Identification of viral DNA by quantitative PCR for EBV and JC virus. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Assessment of the objective response rate, including complete response and partial response, according to the Revised Response Criteria for Malignant Lymphoma of the International Working Group |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |