Back to results

Phase I Study of mPEG-R-Crisantaspase Given IV

Primary Purpose

Hematologic Malignancies

Status

Completed

Phase

Phase 1

Locations

France

Study Type

Interventional

Intervention

mPEG-r-crisantaspase

About this trial

This is an interventional treatment trial for Hematologic Malignancies focused on measuring Leukemia, Lymphoma, C240588.448, C115.378.400

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept 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 E. 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.

Sites / Locations

Centre Henri Becquerel
Hôpital Henri Mondor
Hôpitaux du CHU de Nantes
Hospices Civils de Lyon
Institut Claudius Regaud

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intravenous Erwinia

Arm Description

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose

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

To determine the pharmacokinetic profile as assessed by measurement of serum L-asparaginase enzymatic activity following single and double mPEG-r-chrisantaspace doses.

Full Information

NCT ID

NCT01551524

First Posted

March 8, 2012

Last Updated

May 5, 2015

Sponsor

Jazz Pharmaceuticals

Collaborators

EUSA SAS, The Lymphoma Academic Research Organisation

1. Study Identification

Unique Protocol Identification Number

NCT01551524

Brief Title

Phase I Study of mPEG-R-Crisantaspase Given IV

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 Type

Interventional

2. Study Status

Record Verification Date

February 2015

Overall Recruitment Status

Completed

Study Start Date

March 2012 (undefined)

Primary Completion Date

February 2015 (Actual)

Study Completion Date

February 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Jazz Pharmaceuticals

Collaborators

EUSA SAS, The Lymphoma Academic Research Organisation

4. Oversight

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hematologic Malignancies

Keywords

Leukemia, Lymphoma, C240588.448, C115.378.400

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Intravenous Erwinia

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

mPEG-r-crisantaspase

Other Intervention Name(s)

Asparec

Intervention Description

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%

Primary Outcome Measure Information:

Title

Maximum Tolerated Dose

Description

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Asparaginase Activity in serum

Description

To determine the pharmacokinetic profile as assessed by measurement of serum L-asparaginase enzymatic activity following single and double mPEG-r-chrisantaspace doses.

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 E. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pr Gilles Salles, MD

Organizational Affiliation

Centre Hospitalier Lyon Sud -Chemin du Grand Revoyet

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Xavier Thomas, MD

Organizational Affiliation

Centre Hospitalier Lyon Sud - Chemin du Grand Revoyet

Official's Role

Study Director

Facility Information:

Facility Name

Centre Henri Becquerel

City

Rouen

State/Province

Cedex

ZIP/Postal Code

76038

Country

France

Facility Name

Hôpital Henri Mondor

City

Créteil

ZIP/Postal Code

94010

Country

France

Facility Name

Hôpitaux du CHU de Nantes

City

Nantes

Country

France

Facility Name

Hospices Civils de Lyon

City

Pierre-Bénite

ZIP/Postal Code

69495

Country

France

Facility Name

Institut Claudius Regaud

City

Toulouse

ZIP/Postal Code

31052

Country

France

12. IPD Sharing Statement

Learn more about this trial

Phase I Study of mPEG-R-Crisantaspase Given IV

We'll reach out to this number within 24 hrs