Trial of Oncaspar® and Three Doses of Pegylated Recombinant Asparaginase in Adult Patients With Newly Diagnosed Acute Lymphoblastic Leukaemia

Study Overview
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Brief Summary
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This is an 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). This study will provide first data for determining specific asparaginase doses to yield various durations of L-asparagine (ASN) depletion which are required within different treatment phases of ALL therapy.

Official Title
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A Randomized, Multi-centre, Parallel-group, Open Label, Oncaspar® Controlled Dose Ranging Trial of Three Doses of Pegylated Recombinant Asparaginase in Adult Patients With Newly Diagnosed Acute Lymphoblastic Leukaemia

Conditions
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Acute Lymphoblastic Leukaemia

Intervention / Treatment
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* Drug: Oncaspar
* Drug: PEG-rASNase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously untreated acute lymphoblastic leukaemia (pro-B, common, pre-B, early T, thymic T, mature T) Age 18 years - 55 years Treatment according to German Multicenter Trials for adult Acute Lymphoblastic Leukaemia (GMALL) 07/2003 protocol or subsequent GMALL protocols for patients with de novo ALL Written informed consent Women of child-bearing potential or partner of men with child-bearing potential must use a highly effective method of contraception Negative pregnancy test for women of child-bearing potential Exclusion Criteria: Patients with Philadelphia chromosome (BCR-ABL) positive ALL Severe comorbidity or leukaemia-associated complications Known hypersensitivity to asparaginase History of severe pancreatitis History of thrombosis or pulmonary embolism Pre-existing clinically relevant coagulopathy Liver dysfunction (e.g. acute or current hepatitis, alcohol or drug abuse) or history of clinically relevant liver disease Bilirubin > 1.5 x Upper Limit Norm (ULN) Other current malignancies Severe psychiatric illness or other circumstances which may compromise the cooperation of the patient or the ability to give informed consent Body mass index > 30 kg/m² Known pregnancy, breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEG-rASNase 500<br>500 U/m2 BSA at day 0 | Drug: PEG-rASNase<br>* 500, 1000 or 1500 U/m2 BSA single infusion<br>|
| Experimental: PEG-rASNase 1000<br>1000 U/m2 BSA at day 0 | Drug: PEG-rASNase<br>* 500, 1000 or 1500 U/m2 BSA single infusion<br>|
| Experimental: PEG-rASNase 1500<br>1500 U/m2 at day 0 | Drug: PEG-rASNase<br>* 500, 1000 or 1500 U/m2 BSA single infusion<br>|
| Active Comparator: Oncaspar<br>2000 U/m2 at day 0 | Drug: Oncaspar<br>* 2000 U/m2 BSA, single infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the rate of patients with asparagine depletion 3 weeks after infusion of PEG-rASNase or Oncaspar® in the induction phase. | To compare the rate of patients with asparagine depletion 3 weeks after infusion of PEG-rASNase or Oncaspar® in the induction phase. | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparing of treatment arms | -the rate of patients with asparagine depletion | 62 days | 
| Comparing of treatment arms | the rate of patients with L-asparaginase (ASNase) activity levels in serum > 100 U/L | 62 days | 
| Comparing of treatment arms | the duration of ASNase activity levels in serum > 100 U/L and its variability pharmacokinetic parameters Cmax, t½, CLtotal, Kel, AUC0-t and AUC0-∞ | 62 days | 
| Comparing of treatment arms | the time profiles of ASNase activity and amino acid levels Asparagine (ASN), Aspartic acid (ASP), Glutamine (GLN) and Glutamic acid (GLU) in serum | 62 days | 
| Comparing of treatment arms | the incidence of increased bilirubin grade III/IV | 62 days | 
| Comparing of treatment arms | the incidence of all other adverse events | 62 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asparaginase, ALL