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. |
|
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 |
|
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 number of patients with hypersensitivity reactions to rASNase. |
|
E.2.2 | Secondary objectives of the trial |
- ASNase activity in serum directly before rASNase infusions 1, 2, 4, and 6 during induction treatment, - Concentrations of the amino acids asparagine (ASN), aspartic acid (ASP), glutamine (GLN), and glutamic acid (GLU) in serum directly before rASNase infusions 1, 2, 4, and 6 during induction treatment, -Anti-ASNase antibodies in serum directly before rASNase infusions 1, 2, 4, and 6 during induction treatment, - CR rate and MRD status after induction treatment phase A, - Relapse rate, relapse-free survival and event-free survival at end of follow-up, - Number of patients who could complete their full course of rASNase treatment, - Incidence and severity of adverse events.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Previously untreated T-lineage or precursor B-lineage ALL or biphenotypic leukaemia according to EGIL criteria. - Morphological verification of the diagnosis, confirmed with cyto¬chemistry and immunophenotyping. In case a bone marrow aspiration results in a “dry tap”, a trephine biopsy is advised unless it is possible to confirm the diagnosis by peripheral blood examination. - Age < 1 year at diagnosis. - Written informed consent of the parents or other legally authorised guardian of the patient. - Treatment according to protocol INTERFANT 06 (EudraCT number 2005-004599-19)
|
|
E.4 | Principal exclusion criteria |
-Mature B-lineage ALL, defined by the immunophenotypical presence of surface immunoglobulines or t(8;14) and breakpoint as in B-ALL. - The presence of the t(9;22)(q34;q11) or bcr-abl fusion in the leukaemic cells (if these data are not known, the patient is eligible). - Systemic use of corticosteroids less than 4 weeks before diagnosis. Patients who received corticosteroids by aerosol are eligible. - Known allergy to any ASNase preparation. - Pre-existing known coagulopathy (e.g. haemophilia). - Pre-existing pancreatitis. - Liver insufficiency (bilirubin > 50 µmol/L; SGOT/SGPT > 10 x the upper limit of normal).
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
This non-controlled multicentre phase II study is designed to assess the safety and to describe (in relation to children of higher age) the pharmacodynamics of recombinant ASNase (rASNase) for first-line treatment of infants (< 1 year of age at diagnosis) with de novo acute lymphoblastic leukaemia Primary objective: To determine the number of patients with hypersensitivity reactions to rASNase.
|
|
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 | No |
E.6.7 | Pharmacodynamic | Yes |
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) | 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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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
|
According to the protocol, the end of the follow-up for all patients will be 5 weeks after the last infusion of the last patient (last visit of the last patient). The end of the trail will be defined as the database lock. |
|
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 | |
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 | 6 |