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 version: 14.1 Level: LLT Classification code 10000844 Term: Acute lymphoblastic leukaemia System Organ Class: 10029104 - Neoplasms benign, mal
Conditions
Interventions
Product Name: PEG-rASNase
Product Code: MC0609
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: no INN
CAS Number: no CAS
Current Sponsor code: MC0609
Other descriptive name: PEG-rASNas
Sponsors
medac Gesellschaft für klinische Spezialpräparate mbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Previously untreated acute lymphoblastic leukaemia (pro-B, common, pre-B, early T, thymic T, mature T) 2. Age >= 18 years and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 .;Secondary Objective: -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 ;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 .;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 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 AUC0-8 -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);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 | — |
Countries
Germany
Contacts
Public ContactDepartment Clinical Research
medac Gesellschaft für klinische Spezialpräparate mbH
Outcome results
None listed