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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E.1.1.1 | Medical condition in easily understood language |
Acute lymphoblastic leukemia (ALL) is a fast-growing cancer of the white blood cells with production of unformed cells called blasts, which do not develop and cannot fight infections. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
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 | 10000844 |
E.1.2 | Term | Acute lymphoblastic leukaemia |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Assessment of efficacy and safety of three different doses of pegylated recombinant asparaginase (PEG-rASNase) in comparison to Oncaspar® during treatment of adults with de novo acute lymphoblastic leukaemia (ALL) primary objective:-To compare the rate of patients with asparagine depletion 3 weeks after infusion of PEG-rASNase or Oncaspar® in the induction phase . |
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E.2.2 | Secondary objectives of the trial |
-To compare the rate of patients with asparagine depletion 1, 2, 4, 5, 6, 7 and 9 weeks after study drug administration -To compare the rate of patients with ASNase activity levels in serum > 100 U/L at defined time points -To compare the duration of ASNase activity levels in serum > 100 U/L and its variability -To compare pharmacokinetic parameters Cmax, t½, CLtotal, Kel, AUC0-t and AUC 0-t -To compare the time profiles of ASNase activity and amino acid levels (ASN, ASP, GLN and GLU) in serum -To compare the incidence of increased bilirubin grade III/IV according to CTCAE 3.0 -To compare the incidence of all other adverse events -To determine asparaginase activity and amino acid levels in cerebro-spinal fluid (CSF) -To compare anti-asparaginase and anti-PEG-asparaginase antibodies in serum -To determine the CR rate and MRD status after the induction phase
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Previously untreated acute lymphoblastic leukaemia (pro-B, common, pre-B, early T, thymic T, mature T) 2. Age >= 18 years and <= 55 years 3. Treatment according to GMALL 07/2003 protocol or subsequent GMALL protocols for patients with de novo ALL 4. Written informed consent 5. Women of child-bearing potential or partner of men with child-bearing potential must use a highly effective method of contraception (pearl index < 1%) such as complete sexual abstinence, combined oral contraceptive, hormone IUCD, vaginal hormone ring, transdermal contraceptive patch, contraceptive implant or depot contraceptive injection in combination with a second method of contraception like a condom or a cervical cap / diaphragm with spermicide or surgical sterilisation (vasectomy) in male patients or male partners during the study and at least 6 months thereafter 6. Negative pregnancy test for women of child-bearing potential |
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E.4 | Principal exclusion criteria |
1. Patients with Philadelphia chromosome / Bcr-Abl positive ALL 2. Severe comorbidity or leukaemia-associated complications 3. Known hypersensitivity to asparaginase 4. History of severe pancreatitis 5. History of thrombosis or pulmonary embolism 6. Pre-existing clinically relevant coagulopathy 7. Liver dysfunction (e.g. acute or current hepatitis, alcohol or drug abuse) or history of clinically relevant liver disease 8. Bilirubin > 1.5 x ULN 9. Other current malignancies 10. Severe psychiatric illness or other circumstances which may compromise the cooperation of the patient or the ability to give informed consent 11. Body mass index > 30 kg/m² 12. Known pregnancy, breast feeding |
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E.5 End points |
E.5.1 | Primary end point(s) |
Assessment of the efficacy and safety of three different doses of pegylated recombinant asparaginase (PEG-rASNase) in comparison to Oncaspar® during treatment of adults with de novo acute lymphoblastic leukaemia Primary objective:To compare the rate of patients with asparagine depletion 3 weeks after infusion of PEG-rASNase or Oncaspar® in the induction phase . |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
-after cohorts of 12 patients (3 patients in each treatment arm) -after complition of clinical part of study |
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E.5.2 | Secondary end point(s) |
-To compare: -the rate of patients with asparagine depletion 1, 2, 4, 5, 6, 7 and 9 weeks after study drug administration -rate of patients with L-asparaginase (ASNase) activity levels in serum > 100 U/L at defined time points within 9 weeks after study drug administration -the duration of ASNase activity levels in serum > 100 U/L and its variability -pharmacokinetic parameters Cmax, t½, CLtotal, Kel, AUC0-t and AUC0-∞ -the time profiles of ASNase activity and amino acid levels (ASN, ASP, GLN and GLU) in serum -the incidence of increased bilirubin grade III/IV according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 -the incidence of all other adverse events -anti-asparaginase and anti-PEG-asparaginase antibodies in serum -to determine asparaginase activity and amino acid levels in cerebro-spinal fluid (CSF) - To determine the complete remission (CR) rate and minimal residual disease (MRD) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-after cohorts of 12 patients (3 patients in each treatment arm) -after complition of clinical part of study |
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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 | 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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | 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.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 24 |
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 | No |
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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The end of the CT is defined as the database lock expected 2 months after last patient last visit. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |