Trial of Oncaspar® and Three Doses of Pegylated Recombinant Asparaginase in Adult Patients With Newly Diagnosed Acute Lymphoblastic Leukaemia
Primary Purpose
Acute Lymphoblastic Leukaemia
Status
Terminated
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Oncaspar
PEG-rASNase
Sponsored by
About this trial
This is an interventional treatment trial for Acute Lymphoblastic Leukaemia focused on measuring Asparaginase, ALL
Eligibility Criteria
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
Sites / Locations
- Charité Campus Benjamin Franklin Hämatologie, Onkologie, Transfusionsmedizin Medizinische Klinik III
- Charité University Hospital Campus Virchow
- Universität Bonn, Medizinische Klinik & Poliklinik III
- Städtisches Klinikum Braunschweig Medizinische Klinik III
- Klinikum Carl Gustav Carus der Technischen Universität
- St. Johannes-Hospital
- Universität Erlangen-Nürnberg Med. Klinik V/Hämatologie
- Universitätsklinikum Essen Westdeutsches Tumorzentrum
- Universitätsklinikum Frankfurt Medizinische Klinik II
- Universitätsmedizin Göttingen Hämatologie / Onkologie
- Katholisches Krankenhaus Hagen gGmbH Klinik für Hämatologie und Onkologie
- Asklepios Klinik St. Georg Hämatologie & Stammzelltransplantation
- Asklepios Klinik Altona II. Medizinische Abteilung
- Evangelisches Krankenhaus Medizinische Klinik Hämatologie/Onkologie
- Medical University Hannover
- Universitätsklinikum Heidelberg
- Universitätsklinikum Schleswig-Holstein
- Universität Leipzig José-Carreras-Haus Abt. Hämatologie / Onkologie
- Universitätsmedizin Mainz III. Medizinische Klinik
- Klinikum Schwabing, Klinik für Hämatologie, Onkologie, Immunologie, Palliativmedizin, Infektiologie & Tropenmedizin
- Klinikum Rechts der Isar der TU München III. Medizinische Klinik
- Universitätsklinikum Münster
- Klinikum Nürnberg, 5. Medizinische Klinik
- Klinikum Oldenburg Innere Medizin II
- Klinikum Ernst von Bergmann, Zentrum für Hämatologie, Onkologie und Strahlenheilkunde
- Klinikum der Universität Regensburg
- Universität Rostock, Zentrum für Innere Medizin, Klinik III
- Robert Bosch-Krankenhaus Abt. Hämatologie / Onkologie
- Universitätsklinik Ulm Klinik für Innere Medizin III Zentrum für Innere Medizin
- Klinikum der Universität Würzburg
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Active Comparator
Arm Label
PEG-rASNase 500
PEG-rASNase 1000
PEG-rASNase 1500
Oncaspar
Arm Description
500 U/m2 BSA at day 0
1000 U/m2 BSA at day 0
1500 U/m2 at day 0
2000 U/m2 at day 0
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Comparing of treatment arms
-the rate of patients with asparagine depletion
Comparing of treatment arms
the rate of patients with L-asparaginase (ASNase) activity levels in serum > 100 U/L
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-∞
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
Comparing of treatment arms
the incidence of increased bilirubin grade III/IV
Comparing of treatment arms
the incidence of all other adverse events
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01251809
Brief Title
Trial of Oncaspar® and Three Doses of Pegylated Recombinant Asparaginase in Adult Patients With Newly Diagnosed Acute Lymphoblastic Leukaemia
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2013
Overall Recruitment Status
Terminated
Study Start Date
January 2011 (undefined)
Primary Completion Date
October 2012 (Actual)
Study Completion Date
May 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
medac GmbH
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukaemia
Keywords
Asparaginase, ALL
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
56 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
PEG-rASNase 500
Arm Type
Experimental
Arm Description
500 U/m2 BSA at day 0
Arm Title
PEG-rASNase 1000
Arm Type
Experimental
Arm Description
1000 U/m2 BSA at day 0
Arm Title
PEG-rASNase 1500
Arm Type
Experimental
Arm Description
1500 U/m2 at day 0
Arm Title
Oncaspar
Arm Type
Active Comparator
Arm Description
2000 U/m2 at day 0
Intervention Type
Drug
Intervention Name(s)
Oncaspar
Intervention Description
2000 U/m2 BSA, single infusion
Intervention Type
Drug
Intervention Name(s)
PEG-rASNase
Intervention Description
500, 1000 or 1500 U/m2 BSA single infusion
Primary Outcome Measure Information:
Title
To compare the rate of patients with asparagine depletion 3 weeks after infusion of PEG-rASNase or Oncaspar® in the induction phase.
Description
To compare the rate of patients with asparagine depletion 3 weeks after infusion of PEG-rASNase or Oncaspar® in the induction phase.
Time Frame
3 weeks
Secondary Outcome Measure Information:
Title
Comparing of treatment arms
Description
-the rate of patients with asparagine depletion
Time Frame
62 days
Title
Comparing of treatment arms
Description
the rate of patients with L-asparaginase (ASNase) activity levels in serum > 100 U/L
Time Frame
62 days
Title
Comparing of treatment arms
Description
the duration of ASNase activity levels in serum > 100 U/L and its variability pharmacokinetic parameters Cmax, t½, CLtotal, Kel, AUC0-t and AUC0-∞
Time Frame
62 days
Title
Comparing of treatment arms
Description
the time profiles of ASNase activity and amino acid levels Asparagine (ASN), Aspartic acid (ASP), Glutamine (GLN) and Glutamic acid (GLU) in serum
Time Frame
62 days
Title
Comparing of treatment arms
Description
the incidence of increased bilirubin grade III/IV
Time Frame
62 days
Title
Comparing of treatment arms
Description
the incidence of all other adverse events
Time Frame
62 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicola Gökbuget, MD
Organizational Affiliation
Universitätsklinikum Frankfurt, Medizinische Klinik II, Theodor-Stern-Kai 7, 60590, Frankfurt
Official's Role
Principal Investigator
Facility Information:
Facility Name
Charité Campus Benjamin Franklin Hämatologie, Onkologie, Transfusionsmedizin Medizinische Klinik III
City
Berlin
ZIP/Postal Code
12200
Country
Germany
Facility Name
Charité University Hospital Campus Virchow
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Universität Bonn, Medizinische Klinik & Poliklinik III
City
Bonn
ZIP/Postal Code
53105
Country
Germany
Facility Name
Städtisches Klinikum Braunschweig Medizinische Klinik III
City
Braunschweig
ZIP/Postal Code
38114
Country
Germany
Facility Name
Klinikum Carl Gustav Carus der Technischen Universität
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
St. Johannes-Hospital
City
Duisburg
ZIP/Postal Code
47166
Country
Germany
Facility Name
Universität Erlangen-Nürnberg Med. Klinik V/Hämatologie
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
Universitätsklinikum Essen Westdeutsches Tumorzentrum
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Universitätsklinikum Frankfurt Medizinische Klinik II
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Universitätsmedizin Göttingen Hämatologie / Onkologie
City
Göttingen
ZIP/Postal Code
37075
Country
Germany
Facility Name
Katholisches Krankenhaus Hagen gGmbH Klinik für Hämatologie und Onkologie
City
Hagen
ZIP/Postal Code
58095
Country
Germany
Facility Name
Asklepios Klinik St. Georg Hämatologie & Stammzelltransplantation
City
Hamburg
ZIP/Postal Code
20099
Country
Germany
Facility Name
Asklepios Klinik Altona II. Medizinische Abteilung
City
Hamburg
ZIP/Postal Code
22763
Country
Germany
Facility Name
Evangelisches Krankenhaus Medizinische Klinik Hämatologie/Onkologie
City
Hamm
ZIP/Postal Code
59063
Country
Germany
Facility Name
Medical University Hannover
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Universitätsklinikum Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Universitätsklinikum Schleswig-Holstein
City
Kiel
ZIP/Postal Code
24116
Country
Germany
Facility Name
Universität Leipzig José-Carreras-Haus Abt. Hämatologie / Onkologie
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Universitätsmedizin Mainz III. Medizinische Klinik
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Klinikum Schwabing, Klinik für Hämatologie, Onkologie, Immunologie, Palliativmedizin, Infektiologie & Tropenmedizin
City
München
ZIP/Postal Code
80804
Country
Germany
Facility Name
Klinikum Rechts der Isar der TU München III. Medizinische Klinik
City
München
ZIP/Postal Code
81675
Country
Germany
Facility Name
Universitätsklinikum Münster
City
Münster
ZIP/Postal Code
48129
Country
Germany
Facility Name
Klinikum Nürnberg, 5. Medizinische Klinik
City
Nürnberg
ZIP/Postal Code
90419
Country
Germany
Facility Name
Klinikum Oldenburg Innere Medizin II
City
Oldenburg
ZIP/Postal Code
26133
Country
Germany
Facility Name
Klinikum Ernst von Bergmann, Zentrum für Hämatologie, Onkologie und Strahlenheilkunde
City
Potsdam
ZIP/Postal Code
14467
Country
Germany
Facility Name
Klinikum der Universität Regensburg
City
Regensburg
ZIP/Postal Code
93053
Country
Germany
Facility Name
Universität Rostock, Zentrum für Innere Medizin, Klinik III
City
Rostock
ZIP/Postal Code
18057
Country
Germany
Facility Name
Robert Bosch-Krankenhaus Abt. Hämatologie / Onkologie
City
Stuttgart
ZIP/Postal Code
70376
Country
Germany
Facility Name
Universitätsklinik Ulm Klinik für Innere Medizin III Zentrum für Innere Medizin
City
Ulm
ZIP/Postal Code
89070
Country
Germany
Facility Name
Klinikum der Universität Würzburg
City
Würzburg
ZIP/Postal Code
97070
Country
Germany
12. IPD Sharing Statement
Learn more about this trial
Trial of Oncaspar® and Three Doses of Pegylated Recombinant Asparaginase in Adult Patients With Newly Diagnosed Acute Lymphoblastic Leukaemia
We'll reach out to this number within 24 hrs