Acute Lymphoblastic Leukaemia MedDRA version: 17.1 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 100000004864
Conditions
Interventions
Product Name: GRASPA
Product Code: PF001
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: L-asparaginase encapsulated in erythrcoytes
Current Sponsor code: L-asparaginase encapsulate
Sponsors
ERYTECH Pharma
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patient from 1 to 55 years old - Children and adolescents from 1 up to 17 years - Adults over 18 up to 55 years - Patients with - 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 below 18) Are the trial subjects under 18? yes Number of subjects for this age range: 40 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - 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 transfusionnal 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 phenytoine treatment. - Patient included in previous clinical study less than 6 weeks
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): EXPLORATORY PHASE II AND CONFIRMATORY PHASE III: There are 2 primary endpoints in the study: one regarding Efficacy and one regarding Safety. The study will be declared positive if the 2 primary endpoints are met. Primary endpoint of efficacy The initially specified endpoint for efficacy was : - Efficacy endpoint at end of F2 block (or VANDA) (i.e. Day 28): • Mean duration of asparagine depletion in days throughout F1-F2 blocks. Asparagine depletion will be defined as plasmatic asparagine concentration = 2µM. According to the CHMP advice, this efficacy endpoint was revised to : - Efficacy endpoint at end of induction phase (i.e. day 28): • Duration in days of asparaginase activity >100 IU/L. Primary endpoint of safety • Toxicity endpoint at end of F2 block (or VANDA) : Incidence of allergic reaction, whatever the grade.;Main Objective: Determine the efficacy and safety of GRASPA® at a dose equivalent to 150 IU/kg of L-asparaginase combined with standard polychemotherapy in several populations of patients with first recurrence of ALL Ph-, i.e. children from 1 to 17 years old, adults from 18 to 55 years old, with or without known hypersensitivity to L-asparaginase.;Secondary Objective: to evaluate - the molecular and clinical response rate: minimal residual disease, (MRD) and complete remission (CR), - the safety of GRASPA® compared to the reference L-asparaginase treatment, - the biological efficacy of GRASPA® compared to the reference L-asparaginase treatment by measurement of the total mean duration of plasmatic asparagine depletion in days, - the number of patients with adequate asparagine depletion (i.e. = 2 µM) and without allergic reaction during the induction phase - number of patients with asparaginase activity >100IU/L and without allergic reaction during the induction phase. - the immunogenicity of GRASPA® compared to reference L-asparaginase treatment by the assessment of specific antibodies, - and compare the treatment adheren | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): EXPLORATORY PHASE II • Molecular response rate (MRD). • Percentage of CR patients at F2 block ending. • Biological and clinical toxicity according to NCI-CTCAE (version 3.0) grading, in particular pancreatic, hepatic toxicity, deep vein thrombosis and other coagulation disorders, which are well known adverse events related to L-asparaginase. • Plasma concentrations of asparagine, aspartate, glutamine, glutamate and asparaginase. • Percentage of patient presenting with asparagine depletion (i.e. = 2µM) at different time points. CONFIRMATORY PHASE III: Secondary endpoints listed above are still used and the following are added: • Number of patients with adequate asparagine depletion (i.e. = 2 µM) and without allergic reaction during the induction phase. • Number of patients with asparaginase activity >100 IU/L and without allergic reaction during the induction phase. • Specific anti-L-asparaginase antibodies level. • Ratio of performed / planned injections regarding GRASPA® and reference asparaginase treatment over the total mean duration of study treatment. • At 6, 12, 24, 36 months: o Event free survival rate o Relapse free survival rate o Overall survival rate.;Timepoint(s) of evaluation of this end point: Timepoint(s) of evaluation of Secondary end points described in E.5.2 | — |
Countries
Belgium, Spain
Contacts
Public ContactJerome Bailly
ERYTECH Pharma
Outcome results
None listed