Phase I Study of mPEG-R-Crisantaspase Given IV
This study is an open label, multicenter study with a dose escalation of Asparec® administered once every two to four weeks for two administrations. The primary objective of this study is to determine the Maximum Tolerated Dose following one single dose of Asparec when administered in a population of patients with relapsed or refractory hematological malignancies, as measured by Dose Limiting toxicities. There are secondary objectives which are to evaluate the safety of Asparec and to determine the PK profile as assessed by measurement of plasma L-asparaginase enzymatic activity following single and repeated doses of Asparec. Patients response rate will be evaluated and Anti-Asparec antibodies will be measured.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Dose Escalation Phase I Study of Asparec®(mPEG-R-Crisantaspase) Administered as Intravenous (IV) Infusion in Patients With Relapsed or Refractory Hematological Malignancies|
- Maximum Tolerated Dose [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]To determine the Maximum Tolerated Dose following one single dose of mPEG-r-Crisantaspase when administered in a population of patients with relapsed or refractory hematological malignancies, as measured by Dose Limiting Toxicities.
- Asparaginase Activity in serum [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]To determine the pharmacokinetic profile as assessed by measurement of serum L-asparaginase enzymatic activity following single and double mPEG-r-chrisantaspace doses.
|Study Start Date:||March 2012|
|Study Completion Date:||February 2015|
|Primary Completion Date:||February 2015 (Final data collection date for primary outcome measure)|
|Experimental: Intravenous Erwinia||
IV infusion over 60 minutes of mPEG-r-crisantaspase given once every two or four weeks for two administrations. Based on non-clinical data, 500IU/m2 has been selected as the starting dose. Dose selection will proceed based upon safety and pharmacokinetic data but escalation will not exceed 100%
Other Name: Asparec
Planned sample size: Up to 36 evaluable subjects will be enrolled in the study: a maximum of 30 subjects for the dose escalation phase and up to a maximum of 12 patients in the expansion phase.
Inclusion criteria consists of:
Patients with any relapsed or refractory hematological malignancy, for which standard curative or life prolonging treatment does not exist, or is no longer effective or tolerable.
For the following hematological malignancies, patients must have received at least: Low rade NHL: 3 prior lines of therapy, ALL, aggressive NHL and other hematological malignancies: 2 prior lines of therapy, Aged 18 to 50 years and ECOG performance status of 1, 1 or 2.
All patients will be treated with Asparec once every two to four weeks for two IV administrations infused in 60 minutes. Patients without Disease Progression may receive additional administrations, each administration starting at least 14 days but no later than 28 days after the previous Asparec administration.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01551524
|Centre Henri Becquerel|
|Rouen, Cedex, France, 76038|
|Hôpital Henri Mondor|
|Créteil, France, 94010|
|Hôpitaux du CHU de Nantes|
|Hospices Civils de Lyon|
|Pierre-Bénite, France, 69495|
|Institut Claudius Regaud|
|Toulouse, France, 31052|
|Principal Investigator:||Pr Gilles Salles, MD||Centre Hospitalier Lyon Sud -Chemin du Grand Revoyet|
|Study Director:||Xavier Thomas, MD||Centre Hospitalier Lyon Sud - Chemin du Grand Revoyet|