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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001941 |
E.1.2 | Term | AML |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 assess the tolerability and safety of 2 dose levels of SU11248 in combination with standard induction and consolidation therapy |
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E.2.2 | Secondary objectives of the trial |
To document any anti-AML activity of SU11248 in combination with standard induction and consolidation therapy |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients with primary or secondary acute myeloid leukemia (any FAB type, except M3). • No prior systemic chemotherapy for AML except hydroxyurea. Cytoreductive therapy with hydroxyurea is recommended if WBC is > 50.000/µl, but should cease at least one day prior to starting study medication • Patient age equal or of greater than 60 years • Patients must have FLT3 mutated AML, either ITD or kinase domain mutations • ECOG Performance score 3 or less (Karnofsky Performance Score >40%). • Life expectancy more than four weeks. • Adequate hepatic and renal function, as defined by serum transaminases <2.5x ULN, bilirubin <1.5x ULN. Creatinine <1.5x ULN. • Patients must provide written informed consent to participate in the trial. • Normal heart function on cardiac ultrasound • Prothrombin time (PT) and partial thromboplastin time (PTT) ≤1.5 x ULN • Serum albumin ≥3.0 g/dl • Serum amylase and lipase ≤1.0 x ULN • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
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E.4 | Principal exclusion criteria |
• Treatment with any investigational agent within four weeks. • Known HIV infection • Presence of any medical or psychiatric condition which may limit full compliance with the study, including but not limited to: • Presence of CNS leukaemia • Unresolved toxicity from previous anti-cancer therapy or incomplete recovery from surgery. • Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other thromboembolic event. • Current treatment with therapeutic doses of anticoagulant (low dose Coumadin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed). • Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy). • Pre existing thyroid abnormality of thyroid function that cannot be maintained in the normal range with medication. • Ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2, atrial fibrillation of any Grade, or prolongation of the QTc interval to >450 msec for males or >470 msec for females. • Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Definition of a recommended Phase III dose and determination CTC version 3.0 grade 3-5 non-hematological toxicities of SU11248 in combination with standard induction and consolidation chemotherapy |
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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 | 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 | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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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 | 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 | 5 |
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
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |