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)
Condition: Acute Lymphoblastic Leukemia; Lymphoblastic Lymphoma
MeSH terms: Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Hypersensitivity
Intervention: pegcrisantaspase
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 1 Year
Maximum age: 21 Years
Healthy volunteers: No
Keywords: ALL; LBL

Summary:

      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).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Have a diagnosis of ALL/LBL

          2. Be > 1 to ≤ 21 years of age at study enrollment

          3. Have had a ≥ Grade 2 allergic reaction (Common Terminology Criteria for Adverse Events
             [CTCAE] v4.03) to pegaspargase

          4. Have ≥ 1 dose(s) of pegaspargase remaining in his/her treatment plan

          5. Have a documented SAA level that is below the limit of quantitation per the analytical
             method.

          6. 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.

          7. Subjects must have a performance status corresponding to:

               -  Karnofsky ≥ 50 (for subjects > 16 years of age)

               -  Lansky ≥ 50 (for subjects ≤ 16 years of age)

          8. 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.

          9. 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.

         10. 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.

         11. 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:

          1. Have previously received Erwinia asparaginase

          2. Are receiving another investigational agent or will receive an investigational agent
             in subsequent phases of protocol therapy that include asparaginase

          3. Have a history of ≥ Grade 3 pancreatitis (CTCAE v4.03)

          4. Prior history of a CNS thrombotic event or ≥ Grade 3 (CTCAE v4.03) thrombotic event,
             excluding catheter-associated clots

          5. Prior history of asparaginase-associated ≥ Grade 3 (CTCAE v4.03) hemorrhagic event or
             asparaginase-associated thrombus requiring anticoagulation therapy

          6. Blood triglyceride levels > 500 mg/dL or > 5.6 mmol/L

          7. Hyperglycemia requiring insulin therapy

          8. QTc prolongation ≥ 550 msec

          9. Subjects who in the opinion of the investigator may not be able to comply with the
             safety monitoring requirements of the study

         10. 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.