NCT01518517

Brief Summary

Asparaginase is a cornerstone in the treatment of ALL, but its utility is limited by toxicities including hypersensitivity. Clinical allergy is associated with inactivation of asparaginase by antibodies (A-Abs), which can also neutralize asparaginase without any clinical signs of hypersensitivity (silent inactivation). GRASPA improves pharmacokinetics, tolerability and maintain circulating asparaginase activity due to the protective barrier of the erythrocyte membrane. This study is run to confirm the benefit/risk profile of GRASPA at 150 IU/kg in combination with the COOPRALL regimen in adults and children patients with relapsed ALL, with or without known hypersensitivity to L-asparaginase.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
85

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Dec 2009

Longer than P75 for phase_2

Geographic Reach
2 countries

28 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2009

Completed
2.1 years until next milestone

First Submitted

Initial submission to the registry

January 10, 2012

Completed
16 days until next milestone

First Posted

Study publicly available on registry

January 26, 2012

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2014

Completed
2.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2016

Completed
5.3 years until next milestone

Results Posted

Study results publicly available

February 2, 2022

Completed
Last Updated

February 2, 2022

Status Verified

February 1, 2022

Enrollment Period

4.8 years

First QC Date

January 10, 2012

Results QC Date

August 26, 2021

Last Update Submit

February 1, 2022

Conditions

Acute Lymphoblastic Leukemia, in Relapse

Keywords

acute lymphoblastic leukemiarelapseasparaginase

Outcome Measures

Primary Outcomes (2)

  • Duration of Asparaginase Activity >100 U/L During Induction

    Co-primary efficacy endpoint: duration in days of asparaginase activity \>100 U/L in whole blood during the induction treatment phase: last available date/time of activity \>100 UI/L before activity drops below 100 U/L - date/time of first activity \>100 UI/L. Asparaginase activity is compared for GRASPA versus native ASNase to demonstrate the non-inferiority of GRASPA.

    Induction treatment period (i.e. 28 days)

  • Allergic Reaction During Induction Phase

    Co-primary safety endpoint: allergic reaction regardless of grade during induction phase. Only those reactions that were reported in relation to the treatment to which the patient was randomised were counted.

    Induction treatment period (i.e. 28 days)

Secondary Outcomes (3)

  • Complete Remission (CR)

    Induction treatment period (i.e. 28 days)

  • Overall Survival (OS)

    Overall trial period to 36 months

  • Event Free Survival

    Overall trial period to 36 months

Study Arms (2)

GRASPA

EXPERIMENTAL

Each patient randomized in GRASPA® group is to receive at least 2 and up to 10 administration of GRASPA® 150 IU/kg, in combination with standard chemotherapy (COOPRALL). GRASPA® administration takes place as below: * for induction phase: at Day 4 and D18 (F1-F2 induction ) or at D6 if Vanda induction applies (according disease severity) * for consolidation phase: at Day 6 of R2 / R1 blocks, each time block of chemotherapy is given (up to 8 cycles)

Drug: GRASPA

reference L-asparaginase

ACTIVE COMPARATOR

For patient randomized in control group, reference L-asparaginase 10,000 IU/m² will be administered every 3 days intravenously, in combination with standard chemotherapy (COOPRALL). •for induction phase:at Day 4 , D7, D10, D13 (F1 block ) then at Day 18, D21, D24, D27 (of F2 Blocks). NB: administrations take place at D6, D9, D12 and D15 in case of F1-F2 Induction is replaced by VANDA (according disease severity) •for consolidation phase: at D6, D9, D12 ofR2/R1 blocks, each time block of chemotherapy is given (up to 8 cycles).

Drug: L-asparaginase

Interventions

GRASPADRUG

one injection of GRASPA 150 IU/kg at each cycle of chemotherapy

Also known as: ERY001
GRASPA
L-asparaginaseDRUG

3 to 4 Injections of Native E.coli asparaginase 10000IU/m² (every 3 days) at each cycle of chemotherapy

Also known as: KIDROLASE
reference L-asparaginase

Eligibility Criteria

Age1 Year - 55 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Patient from 1 to 55 years old (Children and adolescents from 1 to 17 years/ Adults from 18 to 55 years)
  • Patients with 1st ALL relapse, which could be either isolated bone marrow relapse, or combined (medullary and extra-medullary) relapse, or extra-medullary isolated relapse; or lymphoblastic lymphoma (excepted Burkitt lymphoma) OR Failure to ALL first line treatment (no complete remission obtained)
  • Patient previously treated with free E.Coli L-asparaginase form or pegylated one
  • Performance Status ≤ 2 (WHO score)
  • Patient informed and consent provided (the 2 parents need to consent when children are below 18)

You may not qualify if:

  • ALL t(9;22) and/or BCR-ABL positive (Philadelphia chromosome positive)
  • Patient with 2nd relapse and over
  • Women of childbearing potential without effective contraception as well as pregnant or breast feeding women
  • Patient unable to receive treatments used in global chemotherapy protocols, due to general or visceral conditions such as:Severe cardiac impairment (NYHA grade 3 or 4 cardiomyopathy)/Serum creatinine 2 x ULN unless related to ALL /ALT or AST 5 x ULN unless related to ALL /Pancreatitis history /Other malignancy that ALL / Severe Infection, HIV positive, active hepatitis related to B or C virus infection / Trisomy 21 / Other serious conditions according to investigator's opinion
  • Known grade 4 allergic reaction to E.Coli L-asparaginase (according NCI-CTCAE, Version 3.0)
  • History of grade 3 transfusional incident
  • Presence of specific anti-erythrocyte antibodies preventing from getting a compatible erythrocyte concentrate for the patient
  • Patient under concomitant treatment likely to cause hemolysis
  • Patient undergoing yellow fever vaccination
  • Patient under phenytoin treatment
  • Patient included in previous clinical study less than 6 weeks ago

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (28)

Hopital Des Enfants Reine Fabiola

Brussels, Belgium

Location

Chr de La Citadelle

Liège, Belgium

Location

Chu D'Angers

Angers, France

Location

Hopital Saint Jacques

Besançon, France

Location

Hopital Pellegrin Enfants

Bordeaux, France

Location

Chu Estaing

Clermont-Ferrand, France

Location

Hopital Henri Mondor

Créteil, France

Location

Chu Grenoble

Grenoble, France

Location

Chru Lille - Hop Jeanne de Flandres

Lille, France

Location

Institut Hematologie Oncologie Pediatrique

Lyon, France

Location

Institut Paoli Calmettes

Marseille, France

Location

Hopital Mere Enfant

Nantes, France

Location

Hotel Dieu

Nantes, France

Location

Hopital de L'Archet 2

Nice, France

Location

Hopital Armand Trousseau

Paris, France

Location

Hopital Robert Debre

Paris, France

Location

Hopital Saint Louis

Paris, France

Location

Hopital Haut-Leveque

Pessac, France

Location

Hopital Lyon Sud

Pierre-Bénite, France

Location

Chru Hopital Sud

Rennes, France

Location

Centre Henri Becquerel

Rouen, France

Location

Chu Hopital Nord

Saint-Etienne, France

Location

Institut Cancerologie de La Loire

Saint-Priest-en-Jarez, France

Location

Hopital de Hautepierre

Strasbourg, France

Location

Chu de Toulouse Enfants

Toulouse, France

Location

Hotel Dieu

Valenciennes, France

Location

Hopital Brabois Enfants

Vandœuvre-lès-Nancy, France

Location

Hopital de Brabois

Vandœuvre-lès-Nancy, France

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-LymphomaRecurrence

Interventions

Asparaginase

Condition Hierarchy (Ancestors)

Leukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

AmidohydrolasesHydrolasesEnzymesEnzymes and Coenzymes

Results Point of Contact

Title
Anne-Sophie Clermont
Organization
Erytech Pharma
anne-sophie.clermont@erytech.com
+33 4 78 78 15 70

Study Officials

  • Yves Bertand, MD

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 10, 2012

First Posted

January 26, 2012

Study Start

December 1, 2009

Primary Completion

September 1, 2014

Study Completion

October 1, 2016

Last Updated

February 2, 2022

Results First Posted

February 2, 2022

Record last verified: 2022-02

Data Sharing

IPD Sharing
Will not share

Locations

BE(2)FR(26)