E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Paediatric patients (6 months to 18 years) diagnosed with AML who are refractory to front line therapy, early first relapse (less than 1 year from diagnosis) and second and subsequent relapse patients. |
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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 | 10000880 |
E.1.2 | Term | Acute myeloid leukaemia |
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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 | 10066764 |
E.1.2 | Term | Acute myeloid leukaemia progression |
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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 |
The main objective of the trial is to establish the maximum tolerated dose of clofarabine when used in combination with daunoXome. |
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E.2.2 | Secondary objectives of the trial |
- To characterise the safety and tolerability of the combination of clofarabine and daunoXome including identification of the dose-limiting toxicities. - To document the overall response rate, including (CR and CRi and PR) in this population. - To describe the durability of response and follow-up of these patients, including the number of patients that undergo stem-cell transplant after re-induction with clofarabine and daunoXome.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Diagnosis of acute myelogenous leukaemia (AML). - Patients must be in first relapse within 12 months of initial diagnosis or refractory to induction therapy or be in second or subsequent relapse. - Patients in first or subsequent relapse must have ≥ 5% blasts in the bone marrow, with or without extramedullary disease AND immunophentypic confirmation of AML. - Patients with refractory AML following induction must have > 20% blasts in the bone marrow. - Age must be between 6 months to 18 years old. - Karnofsky or Lansky score of ≥ 50 - Patients of childbearing potential must have a negative pregnancy test and agree to use an effective birth control method or evidence of post-menopausal status. Post-menopausal status is defined as either radiation induced oophorectomy with last menses >1 year ago; chemotherapy induced menopause with 1 year interval since last menses. - Normal renal function defined as Serum creatinine based on normal range for age/gender - Normal hepatic function defined as: Total bilirubin NORMAL for age. ALT OR AST < 5 x upper limit of normal (ULN) for age (unless it is known to be related to leukaemic involvement). - Cardiac function defined as: shortening fraction of ≥ 29% by echocardiogram LVEF > 58%
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E.4 | Principal exclusion criteria |
- First relapse > 1 year from their initial diagnosis of AML - Patients whose previous daunorubicin equivalent exposure equals or exceeds 450mg/m2. - Isolated extramedullary leukemia. - Symptomatic CNS-involvement. - Any evidence of severe or uncontrolled systemic conditions (e.g., systemic infection) or current unstable or uncompensated respiratory or cardiac conditions which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol. - Concurrent treatment or administration of any other experimental drug or with any other anti-cancer therapy. - Patients unable to be regularly followed up for psychological, social, family or geographic reasons. - Patient with expected non-compliance to toxicity management guidelines
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this trial will be the appearance of Dose Limiting Toxicities. The Maximum Tolerated Dose will be defined by the number of Dose Limiting Toxicities during Cycle 1 of therapy. |
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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 | Information not present in EudraCT |
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 | Yes |
E.7.1.3.1 | Other trial type description |
combination phase I study |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
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) | 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.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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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The end of the trial will be when the last subject undergoing the trial has completed the safety evaluation period.
The entire trial will be stopped when the stated objectives of the trial are achieved.
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |