E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute lymphoblastic leukaemia (ALL) is a clonal disease resulting from genetic mutations and transformation of a single early progenitor lymphoid cell. Uncontrolled expansion of leukaemic blasts in the bone marrow leads to suppression of normal haematopoiesis as well as disseminated infiltration of organs and release of blasts into periphal blood. |
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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 | 10000844 |
E.1.2 | Term | Acute lymphoblastic leukaemia |
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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 |
To determine the rate of patients with complete asparaginase (ASN) depletion in serum during induction treatment and to demonstrate non-inferiority of rASNase compared to Asparaginase medac with respect to this parameter. |
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E.2.2 | Secondary objectives of the trial |
Incidence of patients with hypersensitivity reactions to the first dose of ASNase Incidence of predefined ASNase-typical adverse events observed during induction treatment in both treatment arms Rate of complete ASN depletion in CSF at day 33 Trough levels of ASNase activity in serum just before ASNase infusions 2, 4, 6, and 8 during induction treatment ASNase activity levels in CSF during induction treatment phase A Concentrations of the amino acids ASN, aspartic acid (ASP), glutamine (GLN), and glutamic acid (GLU) in serum and CSF at defined time points during induction treatment Trough levels of ASNase activity and ASN, ASP, GLN, and GLU levels in serum at defined time points during post-induction treatment Anti-ASNase antibodies in serum during repeated administration of ASNase CR rate and MRD status after induction treatment phase A To assess the incedence of edverse events in both tratment arms Further information secondary objectives see Study Protocol
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Previously untreated T-lineage or precursor B-lineage ALL - Patients must have morphological proof of ALL and diagnosis must be made from bone marrow morphology with 25% blasts - Age 1 year to 18 years - Written informed consent - Treatment according to DCOG ALL 10 protocol
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E.4 | Principal exclusion criteria |
- Mature B-lineage ALL - Patients with secondary ALL - Known allergy to any ASNase preparation - General health status according to Karnofsky / Lansky score < 40% - Pre-existing known coagulopathy (e.g. haemophilia) - Pre-existing pancreatitis - Liver insufficiency (Bilirubin > 50 µmol/L; SGOT/SGPT > 10 x ULN) - Other current malignancies - Pregnancy (planned or existent), breast feeding
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of patients with complete ASN depletion in serum during induction treatment. Complete ASN depletion is defined as more then 95% reduction of ASN serum levels compared to the baseline value at all measured time points (always before ASNase infusion 2,4,6,8). If a treatment delay between two consecutive ASNase infusions of more than 4 days has occurred, the next scheduled sample for ASN depletion will not be counted. A patient is evaluable for the primary endpoint if ASN levels are available from at least 3 of the 4 scheduled time points. If a baseline ASN value for a special patient is not available for any reason, an average ASN baseline level will be calculated from all patients and taken as reference. If an ASN value before ASNase infusion 2, 4, 6, or 8 is below the lower limit of quantification (LLOQ) it will be counted as half of LLOQ.
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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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
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 | 7 |
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 | 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
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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 | 7 |
E.8.9.1 | In the Member State concerned days | 0 |