Patients with acute lymphoblastic leukemia with allergy against PEG-asparaginase
Conditions
Sponsors
Department of pediatrics, Aarhus University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria: 1. Male or female aged 1-45 years at diagnosis of ALL 2. First line non-high risk (HR) ALL patients enrolled in NOPHO ALL 2008 or ALLTogether pilot protocol including PEG-asparaginase regimen 3. Documented hypersensitivity reaction to PEG-asparaginase with either: • Clinical allergy to PEG- (mild/severe) OR Serum asparaginase activity below the lower level of quantification 4. Karnofsky/Lansky score = 50. 5. Ability to understand, and willingness to sign, a written informed consent document and to comply with the scheduled visits, treatment plans, laboratory tests, and other study procedures. For patients under 18 years of age, either both parents or the legally appointed representatives will need to provide consent. Are the trial subjects under 18? yes Number of subjects for this age range: 50 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 5 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion Criteria: 1. Philadelphia chromosome positive ALL. 2. Participation in another clinical trial interfering with the study therapy. 3. Uncontrolled intercurrent illness including, but not limited to, receiving combination antiretroviral therapy or patients with severe or systemic infection, or psychiatric illness/social situations that would limit compliance with study requirements. 4. Other severe acute/chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study. 5. Pregnant or lactating females . 6. Inadequate organ functions, which prohibit further asparaginase administration 7. History of grade 3 or higher transfusion reactions or any contraindication to receive blood transfusion. Presence of specific anti-erythrocytes antibodies (auto-antibodies or anti-public antibodies) preventing from getting a compatible packed Red Blood Cells for the patient. 8. Patient under concomitant treatment likely to cause hemolysis.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Main objectives of this study are to evaluate the pharmakinetic and pharmacodynamic profile of eryaspase administered to patients who experience a PEG-asparaginase hypersensitivity event during treatment with the multi-agent NOPHO ALL 2008 or ALLTogether chemotherapy for the treatment of children and adult patients with ALL;Secondary Objective: Evaluation of the immunogenicity of eryaspase determined by assessment of anti-L-asparaginase-antibodies. Evaluation of the overall safety and tolerability of eryaspase in combination with multi-agent chemotherapy (according to NOPHO ALL 2008 or ALLTogether pilot protocol). Finally, the effect of eryaspase on the concurrent maintenance therapy with 6-mercaptopurine and methotrexate will be evaluated. ;Primary end point(s): •The safety and tolerability of eryaspase in combination with standard multi-agent NOPHO ALL 2008 or ALLTogether chemotherapy assessed during eryaspase treatment period according to potential toxicities defined in "the adverse experience section". •Pharmacokinetic parameters: Total activity (at time points listed in Section 9.4) will be measured. The main pharmacokinetic parameters will be assessed: Cmax; Tmax; T1/2 (half-life time); Vss (Distribution Volume at steady state), MRT (Mean Residence Time) and clearance. Percentage of patients with asparaginase activity >100 IU/L. •Pharmacodynamic profile: Plasma and CSF concentrations of amino-acids: (asparagine, aspartate, glutamine, glutamate) •Immunogenicity: titers of anti-asparaginase antibodies • Safety: incidence of hypersensitivity (allergic reactions and silent inactivation) at the end os asparaginase treatment.;Timepoint(s) of evaluation of this end point: Inclusion of patients are expected to start in January 2017 and will end when 50 patients are included or in February 2020 at the latest. Patients will be followed one month after last administration. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Secondary endpoints are to evaluate toxicity according to the PdL consensus definitions. •Levels of maintenance metabolites ;Timepoint(s) of evaluation of this end point: Inclusion of patients are expected to start in January 2017 and will end when 50 patients are included or in February 2020 at the latest. Patients will be followed one month after last administration. | — |
Countries
Denmark, Estonia, Finland, Lithuania, Norway, Sweden
Contacts
Public ContactLine Stensig Lynggaard
Department of pediatrics, Aarhus University Hospital
Outcome results
None listed