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

Sponsor

medac GmbH (Industry)

Overall Status

Terminated

CT.gov ID

NCT01251809

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

1.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukaemia	Drug: Oncaspar Drug: PEG-rASNase	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

56 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jan 1, 2011

Actual Primary Completion Date :

Oct 1, 2012

Actual Study Completion Date :

May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PEG-rASNase 500 500 U/m2 BSA at day 0	Drug: PEG-rASNase 500, 1000 or 1500 U/m2 BSA single infusion
Experimental: PEG-rASNase 1000 1000 U/m2 BSA at day 0	Drug: PEG-rASNase 500, 1000 or 1500 U/m2 BSA single infusion
Experimental: PEG-rASNase 1500 1500 U/m2 at day 0	Drug: PEG-rASNase 500, 1000 or 1500 U/m2 BSA single infusion
Active Comparator: Oncaspar 2000 U/m2 at day 0	Drug: Oncaspar 2000 U/m2 BSA, single infusion

Outcome Measures

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. [3 weeks]
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 [62 days]
-the rate of patients with asparagine depletion
Comparing of treatment arms [62 days]
the rate of patients with L-asparaginase (ASNase) activity levels in serum > 100 U/L
Comparing of treatment arms [62 days]
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 [62 days]
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 [62 days]
the incidence of increased bilirubin grade III/IV
Comparing of treatment arms [62 days]
the incidence of all other adverse events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Charité Campus Benjamin Franklin Hämatologie, Onkologie, Transfusionsmedizin Medizinische Klinik III	Berlin	Germany	12200
2	Charité University Hospital Campus Virchow	Berlin	Germany	13353
3	Universität Bonn, Medizinische Klinik & Poliklinik III	Bonn	Germany	53105
4	Städtisches Klinikum Braunschweig Medizinische Klinik III	Braunschweig	Germany	38114
5	Klinikum Carl Gustav Carus der Technischen Universität	Dresden	Germany	01307
6	St. Johannes-Hospital	Duisburg	Germany	47166
7	Universität Erlangen-Nürnberg Med. Klinik V/Hämatologie	Erlangen	Germany	91054
8	Universitätsklinikum Essen Westdeutsches Tumorzentrum	Essen	Germany	45147
9	Universitätsklinikum Frankfurt Medizinische Klinik II	Frankfurt	Germany	60590
10	Universitätsmedizin Göttingen Hämatologie / Onkologie	Göttingen	Germany	37075
11	Katholisches Krankenhaus Hagen gGmbH Klinik für Hämatologie und Onkologie	Hagen	Germany	58095
12	Asklepios Klinik St. Georg Hämatologie & Stammzelltransplantation	Hamburg	Germany	20099
13	Asklepios Klinik Altona II. Medizinische Abteilung	Hamburg	Germany	22763
14	Evangelisches Krankenhaus Medizinische Klinik Hämatologie/Onkologie	Hamm	Germany	59063
15	Medical University Hannover	Hannover	Germany	30625
16	Universitätsklinikum Heidelberg	Heidelberg	Germany	69120
17	Universitätsklinikum Schleswig-Holstein	Kiel	Germany	24116
18	Universität Leipzig José-Carreras-Haus Abt. Hämatologie / Onkologie	Leipzig	Germany	04103
19	Universitätsmedizin Mainz III. Medizinische Klinik	Mainz	Germany	55131
20	Klinikum Schwabing, Klinik für Hämatologie, Onkologie, Immunologie, Palliativmedizin, Infektiologie & Tropenmedizin	München	Germany	80804
21	Klinikum Rechts der Isar der TU München III. Medizinische Klinik	München	Germany	81675
22	Universitätsklinikum Münster	Münster	Germany	48129
23	Klinikum Nürnberg, 5. Medizinische Klinik	Nürnberg	Germany	90419
24	Klinikum Oldenburg Innere Medizin II	Oldenburg	Germany	26133
25	Klinikum Ernst von Bergmann, Zentrum für Hämatologie, Onkologie und Strahlenheilkunde	Potsdam	Germany	14467
26	Klinikum der Universität Regensburg	Regensburg	Germany	93053
27	Universität Rostock, Zentrum für Innere Medizin, Klinik III	Rostock	Germany	18057
28	Robert Bosch-Krankenhaus Abt. Hämatologie / Onkologie	Stuttgart	Germany	70376
29	Universitätsklinik Ulm Klinik für Innere Medizin III Zentrum für Innere Medizin	Ulm	Germany	89070
30	Klinikum der Universität Würzburg	Würzburg	Germany	97070