Phase I Study of mPEG-R-Crisantaspase Given IV

Sponsor

Jazz Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01551524

Collaborator

EUSA SAS (Other), The Lymphoma Academic Research Organisation (Other)

Enrollment

Locations

Arm

35.1

Duration (Months)

7.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Malignancies	Biological: mPEG-r-crisantaspase	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

36 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Mar 1, 2012

Actual Primary Completion Date :

Feb 1, 2015

Actual Study Completion Date :

Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intravenous Erwinia	Biological: mPEG-r-crisantaspase 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 Names: Asparec

Arm

Intervention/Treatment

Experimental: Intravenous Erwinia

Biological: mPEG-r-crisantaspase

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 Names:

Asparec

Outcome Measures

Primary Outcome Measures

Maximum Tolerated Dose [6 months]
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.

Secondary Outcome Measures

Asparaginase Activity in serum [6 months]
To determine the pharmacokinetic profile as assessed by measurement of serum L-asparaginase enzymatic activity following single and double mPEG-r-chrisantaspace doses.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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 grade NHL:
3 prior lines of therapy and ALL,
aggressive NHL and other hematological malignancies:
2 prior lines of therapy.
Ages 18 to 50 years and
ECOG performance status of 0, 1 or 2,
ability to understand and to sign a written informed consent and
have a life expectancy of greater than or equal to 90 days

Exclusion Criteria:

Any active CNS disease,
previous greater than or equal to grade 3 allergic reaction to Erwinase,
patients who have experienced a greater than or equal to grade 3 allergic reaction to

coli L-asparaginase and who have never received E. chrysanthemi L-asparaginase after the occurrence of this reaction,

WBC count greater than 20 Gica/L, any of the following laboratory abnormalities if not due to hematologic malignancy (calculated creatinine clearance less than 50 mL/min,
serum SGOT/AST or SGPT?ALT greater than 2.5 x upper limit of normal,
serum total bilirubin greater than 2.0 mg/dL, except in the case of hemolytic anemia.
Patients cannot have a history of greater than or equal to grade 2 pancreatitis,
any history of allogeneic transplant,
receiving steroid therapy with a dose greater than 20 mg/day,
known HIV positive serology,
active hepatitis B or C,
any serious active disease or comorbid medical condition or psychiatric illness that would prevent the subject from signing the informed consent.
Pregnant or lactating females or women of child bearing potential not willing to use an adequate method of birth control for the duration of the study are not eligible.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centre Henri Becquerel	Rouen	Cedex	France	76038
2	Hôpital Henri Mondor	Créteil		France	94010
3	Hôpitaux du CHU de Nantes	Nantes		France
4	Hospices Civils de Lyon	Pierre-Bénite		France	69495
5	Institut Claudius Regaud	Toulouse		France	31052

Sponsors and Collaborators

Jazz Pharmaceuticals
EUSA SAS
The Lymphoma Academic Research Organisation

Investigators

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