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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
medac GmbH
ClinicalTrials.gov Identifier:
NCT01251809
First received: November 26, 2010
Last updated: May 17, 2013
Last verified: May 2013
  Purpose

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 Intervention Phase
Acute Lymphoblastic Leukaemia
Drug: Oncaspar
Drug: PEG-rASNase
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by medac GmbH:

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. [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 62 days ] [ Designated as safety issue: No ]
    -the rate of patients with asparagine depletion

  • Comparing of treatment arms [ Time Frame: 62 days ] [ Designated as safety issue: No ]
    the rate of patients with L-asparaginase (ASNase) activity levels in serum > 100 U/L

  • Comparing of treatment arms [ Time Frame: 62 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 62 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 62 days ] [ Designated as safety issue: Yes ]
    the incidence of increased bilirubin grade III/IV

  • Comparing of treatment arms [ Time Frame: 62 days ] [ Designated as safety issue: Yes ]
    the incidence of all other adverse events


Estimated Enrollment: 56
Study Start Date: January 2011
Study Completion Date: May 2013
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01251809

Locations
Germany
Charité Campus Benjamin Franklin Hämatologie, Onkologie, Transfusionsmedizin Medizinische Klinik III
Berlin, Germany, 12200
Charité University Hospital Campus Virchow
Berlin, Germany, 13353
Universität Bonn, Medizinische Klinik & Poliklinik III
Bonn, Germany, 53105
Städtisches Klinikum Braunschweig Medizinische Klinik III
Braunschweig, Germany, 38114
Klinikum Carl Gustav Carus der Technischen Universität
Dresden, Germany, 01307
St. Johannes-Hospital
Duisburg, Germany, 47166
Universität Erlangen-Nürnberg Med. Klinik V/Hämatologie
Erlangen, Germany, 91054
Universitätsklinikum Essen Westdeutsches Tumorzentrum
Essen, Germany, 45147
Universitätsklinikum Frankfurt Medizinische Klinik II
Frankfurt, Germany, 60590
Universitätsmedizin Göttingen Hämatologie / Onkologie
Göttingen, Germany, 37075
Katholisches Krankenhaus Hagen gGmbH Klinik für Hämatologie und Onkologie
Hagen, Germany, 58095
Asklepios Klinik Altona II. Medizinische Abteilung
Hamburg, Germany, 22763
Asklepios Klinik St. Georg Hämatologie & Stammzelltransplantation
Hamburg, Germany, 20099
Evangelisches Krankenhaus Medizinische Klinik Hämatologie/Onkologie
Hamm, Germany, 59063
Medical University Hannover
Hannover, Germany, 30625
Universitätsklinikum Heidelberg
Heidelberg, Germany, 69120
Universitätsklinikum Schleswig-Holstein
Kiel, Germany, 24116
Universität Leipzig José-Carreras-Haus Abt. Hämatologie / Onkologie
Leipzig, Germany, 04103
Universitätsmedizin Mainz III. Medizinische Klinik
Mainz, Germany, 55131
Klinikum Schwabing, Klinik für Hämatologie, Onkologie, Immunologie, Palliativmedizin, Infektiologie & Tropenmedizin
München, Germany, 80804
Klinikum Rechts der Isar der TU München III. Medizinische Klinik
München, Germany, 81675
Universitätsklinikum Münster
Münster, Germany, 48129
Klinikum Nürnberg, 5. Medizinische Klinik
Nürnberg, Germany, 90419
Klinikum Oldenburg Innere Medizin II
Oldenburg, Germany, 26133
Klinikum Ernst von Bergmann, Zentrum für Hämatologie, Onkologie und Strahlenheilkunde
Potsdam, Germany, 14467
Klinikum der Universität Regensburg
Regensburg, Germany, 93053
Universität Rostock, Zentrum für Innere Medizin, Klinik III
Rostock, Germany, 18057
Robert Bosch-Krankenhaus Abt. Hämatologie / Onkologie
Stuttgart, Germany, 70376
Universitätsklinik Ulm Klinik für Innere Medizin III Zentrum für Innere Medizin
Ulm, Germany, 89070
Klinikum der Universität Würzburg
Würzburg, Germany, 97070
Sponsors and Collaborators
medac GmbH
Investigators
Principal Investigator: Nicola Gökbuget, MD Universitätsklinikum Frankfurt, Medizinische Klinik II, Theodor-Stern-Kai 7, 60590, Frankfurt
  More Information

No publications provided

Responsible Party: medac GmbH
ClinicalTrials.gov Identifier: NCT01251809     History of Changes
Other Study ID Numbers: MC-PEGASP.1/adults
Study First Received: November 26, 2010
Last Updated: May 17, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by medac GmbH:
Asparaginase
ALL

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Pegaspargase
Asparaginase
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 16, 2014