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

Acute Lymphoblastic Leukaemia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01251809
• Other study ID #: MC-PEGASP.1/adults
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: November 26, 2010
• Last updated: May 17, 2013
• Start date: January 2011
• Est. completion date: May 2013

Study information

• Verified date: May 2013
• Source: medac GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 56
• Est. completion date: May 2013
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukaemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Oncaspar
2000 U/m2 BSA, single infusion
• PEG-rASNase
500, 1000 or 1500 U/m2 BSA single infusion

Locations

Country	Name	City	State
Germany	Charité Campus Benjamin Franklin Hämatologie, Onkologie, Transfusionsmedizin Medizinische Klinik III	Berlin
Germany	Charité University Hospital Campus Virchow	Berlin
Germany	Universität Bonn, Medizinische Klinik & Poliklinik III	Bonn
Germany	Städtisches Klinikum Braunschweig Medizinische Klinik III	Braunschweig
Germany	Klinikum Carl Gustav Carus der Technischen Universität	Dresden
Germany	St. Johannes-Hospital	Duisburg
Germany	Universität Erlangen-Nürnberg Med. Klinik V/Hämatologie	Erlangen
Germany	Universitätsklinikum Essen Westdeutsches Tumorzentrum	Essen
Germany	Universitätsklinikum Frankfurt Medizinische Klinik II	Frankfurt
Germany	Universitätsmedizin Göttingen Hämatologie / Onkologie	Göttingen
Germany	Katholisches Krankenhaus Hagen gGmbH Klinik für Hämatologie und Onkologie	Hagen
Germany	Asklepios Klinik Altona II. Medizinische Abteilung	Hamburg
Germany	Asklepios Klinik St. Georg Hämatologie & Stammzelltransplantation	Hamburg
Germany	Evangelisches Krankenhaus Medizinische Klinik Hämatologie/Onkologie	Hamm
Germany	Medical University Hannover	Hannover
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Universitätsklinikum Schleswig-Holstein	Kiel
Germany	Universität Leipzig José-Carreras-Haus Abt. Hämatologie / Onkologie	Leipzig
Germany	Universitätsmedizin Mainz III. Medizinische Klinik	Mainz
Germany	Klinikum Rechts der Isar der TU München III. Medizinische Klinik	München
Germany	Klinikum Schwabing, Klinik für Hämatologie, Onkologie, Immunologie, Palliativmedizin, Infektiologie & Tropenmedizin	München
Germany	Universitätsklinikum Münster	Münster
Germany	Klinikum Nürnberg, 5. Medizinische Klinik	Nürnberg
Germany	Klinikum Oldenburg Innere Medizin II	Oldenburg
Germany	Klinikum Ernst von Bergmann, Zentrum für Hämatologie, Onkologie und Strahlenheilkunde	Potsdam
Germany	Klinikum der Universität Regensburg	Regensburg
Germany	Universität Rostock, Zentrum für Innere Medizin, Klinik III	Rostock
Germany	Robert Bosch-Krankenhaus Abt. Hämatologie / Onkologie	Stuttgart
Germany	Universitätsklinik Ulm Klinik für Innere Medizin III Zentrum für Innere Medizin	Ulm
Germany	Klinikum der Universität Würzburg	Würzburg

Sponsors (1)

Lead Sponsor	Collaborator
medac GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Comparing of treatment arms	-the rate of patients with asparagine depletion	62 days	No
Secondary	Comparing of treatment arms	the rate of patients with L-asparaginase (ASNase) activity levels in serum > 100 U/L	62 days	No
Secondary	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 AUC0-8	62 days	No
Secondary	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	No
Secondary	Comparing of treatment arms	the incidence of increased bilirubin grade III/IV	62 days	Yes
Secondary	Comparing of treatment arms	the incidence of all other adverse events	62 days	Yes