E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Accelerated phase Chronic Myeloid Leukaemia (CML). |
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MedDRA Classification |
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 assess the efficacy and safety of subcutaneous HHT in the management of patients with accelerated phase Chronic Myeloid Leukaemia (CML) who are refractory to, or have relapsed on imatinib mesylate. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the cytogenetic and molecular response to the IMP. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
a) Male or female patients aged 18 to 80 years. b) Patients diagnosed with Ph chromosome-positive or BCR-ABL positive CML in the accelerated phase confirmed by a bone marrow aspirate and/or biopsy including cytogenetics and molecular analysis that must be completed within 28 days prior to initiation of HHT c) Patients who have failed to respond to, or have relapsed on imatinib d) Estimated life expectancy of at least 12 weeks. e) Adequate performance status as defined by a grading of 2 or better on the ECOG Performance Status Criteria f) Female patients of child-bearing potential willing to use adequate contraception (oral contraceptive pill, IUD, surgical sterilization, depot injection, contraceptive patches or barrier method in combination with a spermicide) for the duration of and at least one month after the last dose of investigational product. g) Male patients willing to use adequate contraception for the duration of and at least three months after the last dose of investigational product. h) Patients who have given written informed consent having read and understood the subject information sheet. |
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E.4 | Principal exclusion criteria |
a) Patients planned for allogeneic transplantation before the end of induction period. b) Prior stem cell transplantation. c) Patients previously treated with combination chemotherapy or autografting for accelerated phase disease. d) Patients with previous blastic phase. e) Subjects previously treated with HHT. f) Female patients who are pregnant (confirmed by a serum pregnancy test) or lactating. g) For patients who have received another investigational anti-leukemic product, a wash-out period of 2 times half-life of the product must be observed before initiation of treatment with HHT (at least 48h of wash-out). In case of grade 3-4 hematological toxicity related to any other investigational anti-leukemic product, patients should not begin treatment with HHT until blood count recovery. h) Anti-leukemic agents, other than hydroxyurea (HU) or anagrelide, within seven days prior to the initiation of treatment with HHT. Imatinib have to be stopped at least 48 hours before starting therapy with HHT. In case of grade 3-4 hematological toxicity related to imatinib, patients should not begin treatment with HHT until blood counts recovery. i) NYHA class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart failure. j) Creatinine levels more than 3 x ULN (upper limit of normal range) at the laboratory where the analysis was performed. k) Total serum bilirubin more than 3 x ULN in subjects without clinically suspected leukemic involvement of the liver. l) AST (SGOT) or ALT (SGPT) more than 5 x ULN in subjects without clinically suspected leukemic involvement of the liver. m) Any other reason, which the Investigator feels, would preclude safe inclusion of the subject. |
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E.5 End points |
E.5.1 | Primary end point(s) |
A. Haematological response rate to treatment at the end of the induction phase (including the rate of complete haematological response and the rate of return to chronic phase.
B. Safety: rate and grade of non-haematological adverse events and rate and duration of grade 4 haematological toxicity (as defined by the CTC-NCI criteria).
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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 | Information not present in EudraCT |
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 | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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
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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 | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |