Ph 1 Study of ADI PEG 20 in Pediatric Subjects Who Are Argininosuccinate Synthetase (ASS) Deficient

This phase 1 study will use a classic 3 dose levels by 3 patients per dose level design. Once the maximum tolerated dose is reached, additional patients may be enrolled at that dose level.

Inclusion criteria

• Prior diagnosis of failed current standard treatment(s), or AEs associated with prior systemic agent(s) that resulted in discontinuance of that agent(s).
• Argininosuccinate synthetase deficient tumor.
• Measurable disease as assessed by >5% blasts on bone marrow aspirate for patients with leukemia or using RECIST 1.1 criteria for solid tumors.
• Age 4 to ≤ 18 years.
• No prior systemic treatment for the tumor in the last 2 weeks for solid tumors and 1 week for leukemia, except hydroxyurea used only to control very high WBC.
• Fully recovered from any prior surgery and no major surgery within 4 weeks of initiating treatment. Surgery for placement of vascular access devices is acceptable.
• Female subjects of 10 years and older and male subjects must be asked to use appropriate contraception for both the male and female for the duration of the study.
• No concurrent investigational studies are allowed.
• For solid tumor subjects only: Absolute neutrophil count (ANC) >750/µL.
• For solid tumor subjects only: Platelets >50,000/µL.
• For solid tumor subjects only: Serum uric acid ≤ 8 mg/dL (with or without medication control).
• Serum creatinine ≤ 1.5 x the upper limit of normal range, or, if serum creatinine >1.5 x the upper limit of normal range, then the creatinine clearance must be ≥ 60 mL/min.

Exclusion criteria

• Serious infection requiring treatment with systemically administered antibiotics at the time of study entrance.
• Pregnancy or lactation.
• Expected non-compliance.
• Uncontrolled intercurrent illness.
• Subjects who have had any anticancer treatment prior to entering the study and have not recovered to baseline or ≤ Grade 1 AEs due to agents administered.
• Subjects who had been treated with ADI-PEG 20 previously.
• History of seizure disorder not related to underlying cancer.
• Known HIV positivity.