A Dose Confirmation and Pharmacokinetic Study of Pegcrisantaspase Administered as Intravenous (IV) Infusion in Children and Young Adults With Acute Lymphoblastic Leukemia (ALL) /Lymphoblastic Lymphoma (LBL). Following Hypersensitivity to Pegaspargase (Oncaspar)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness,safety, and dosage of pegcrisantaspase in patients with Acute Lymphoblastic Leukemia (ALL) / Lymphoblastic Lymphoma (LBL).

Detailed Description
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The purpose of the study was to assess the response rate in children and young adults with ALL/LBL and hypersensitivity to pegaspargase defined as the proportion of subjects having a serum asparaginase activity (SAA) level of ≥ 0.1 IU/mL 14 days following the first IV pegcrisantaspase dose in Course 1. Also, to assess the safety of IV pegcrisantaspase therapy in children and young adults with ALL/LBL with hypersensitivity to pegaspargase.

Official Title
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A Dose Confirmation and Pharmacokinetic Study of Pegcrisantaspase Administered as Intravenous (IV) Infusion in Children and Young Adults With Acute Lymphoblastic Leukemia (ALL) /Lymphoblastic Lymphoma (LBL). Following Hypersensitivity to Pegaspargase (Oncaspar)

Conditions
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Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma

Intervention / Treatment
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* Drug: pegcrisantaspase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of ALL/LBL Be > 1 to ≤ 21 years of age at study enrollment Have had a ≥ Grade 2 allergic reaction (Common Terminology Criteria for Adverse Events [CTCAE] v4.03) to pegaspargase Have ≥ 1 dose(s) of pegaspargase remaining in his/her treatment plan Have a documented SAA level that is below the limit of quantitation per the analytical method. Subjects must have, in the opinion of the investigator, fully recovered from prior allergic reaction to pegaspargase. Subjects must have completed antihistamine, epinephrine, and/or corticosteroid treatment for the allergic reaction ≥ 24 hours prior to pegcrisantaspase administration. Subjects must have a performance status corresponding to: Karnofsky ≥ 50 (for subjects > 16 years of age) Lansky ≥ 50 (for subjects ≤ 16 years of age) Adequate Renal Function Defined as: Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m2 or A serum creatinine based on age/gender as follows: Age Maximum Serum Creatinine (mg/dL) Male Female 1 to < 2 years 0.6 0.6 2 to < 6 years 0.8 0.8 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4 ≥ 16 years 1.7 1.4 The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR (Schwartz & Gauthier 1985) utilizing child length and stature data published by the CDC. Adequate Liver Function defined as: Bilirubin levels ≤ 2.5x ULN for age, and Direct (conjugated) Bilirubin < 0.5 mg/dLSGPT (ALT) ≤ 225 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L. Subjects who are sexually active must agree to use a medically acceptable method of contraception throughout the entire study period and for 4 weeks after the study is completed. Medically acceptable methods of contraception that may be used by the subject and/or the partner include abstinence, birth control pills or patches, diaphragm and spermicide, condom and vaginal spermicide, surgical sterilization, postmenopausal, vasectomy (>6 months prior to baseline), and progestin implant or injection. Able to understand and to sign a written informed consent. All subjects and/or their parent or a legally authorized representative must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines. Exclusion Criteria: Have previously received Erwinia asparaginase Are receiving another investigational agent or will receive an investigational agent in subsequent phases of protocol therapy that include asparaginase Have a history of ≥ Grade 3 pancreatitis (CTCAE v4.03) Prior history of a CNS thrombotic event or ≥ Grade 3 (CTCAE v4.03) thrombotic event, excluding catheter-associated clots Prior history of asparaginase-associated ≥ Grade 3 (CTCAE v4.03) hemorrhagic event or asparaginase-associated thrombus requiring anticoagulation therapy Blood triglyceride levels > 500 mg/dL or > 5.6 mmol/L Hyperglycemia requiring insulin therapy QTc prolongation ≥ 550 msec Subjects who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study Subjects who have any serious active disease or co-morbid medical condition (according to investigator's decision), or psychiatric illness that would prevent the subject from signing the informed consent form, assent form or informed consent form by parents, pending institutional requirements, or per investigator's opinion, would prevent the subject from completing one course of pegcrisantaspase. Pregnant or lactating females or females of childbearing potential not willing to use an adequate method of birth control for the duration of the study. Female subjects who are lactating who do not agree to stop breast-feeding.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pegcrisantaspase<br> | Drug: pegcrisantaspase<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Response Rate in Children & Young Adults With ALL/LBL and Hypersensitivity to Pegaspargase Defined as the Proportion of Subjects Having a Serum Asparaginase Activity (SAA) Level of >= 0.1 IU/mL Following the First IV Dose in Course 1 |  | 15 days during Course 1 | 
| The Serum Asparaginase Activity 14 Days After the First Infusion of Study Drug and the Adverse Events in All Participants. |  | 1 Year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Pharmakokinetic (PK) Profile of IV Pegcrisantaspase in Children and Young Adults With ALL/LBL and Hypersensitivity to Pegaspargase. Pharmakokinetic Profiles to be Assessed Are: Half Life, Elimination Rate, Tmax, Cmax, AUC. |  | 14 Days | 
| The SAA Levels Over Time Following Repeated Administration in Children and Young Adults ALL/LBL and Hypersensitivity to Pegaspargase |  | 30 Days | 
| The Immunogenicity of IV Pegcristaspase by Testing Anti-pegcrisantaspase and Anti-PEG Binding and Neutralizing Antibodies |  | 30 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LBL, ALL