A Study Evaluating the Safety and Activity of Pegylated Recombinant Human Arginase (BCT-100)

A Phase I/II Study Evaluating the Safety and Activity of Pegylated Recombinant Human Arginase (BCT-100) in Relapsed/Refractory Cancers of Children and Young Adults

PARC is an international phase I/II trial evaluating the safety and activity of pegylated recombinant human arginase (BCT-100) in children and young people with relapsed/refractory leukaemia, neuroblastoma, sarcoma and high grade gliomas (brain cancers).

Currently the outcomes for these patients are poor and the therapeutic options are limited with a significant toxicity burden. Therefore new treatments which work in different ways to standard chemotherapy are urgently needed. Research has shown that arginine (a nutrient) is important in the survival of cancer cells. BCT-100 is a drug which can deplete arginine levels and starve cancer cells - a completely new approach. BCT-100 has been tested in adults and shown to be active with almost no side-effects. This trial will test whether this dose of BCT-100 is also safe and active in children with relapsed/refractory leukaemia, neuroblastoma, sarcoma and high grade glioma. The trial will also study how BCT-100 is broken down in the body and look for new biological markers of treatment response. Up to 64 children with relapsed cancers will be recruited over 2 years.

Inclusion Criteria:

• Aged 1- <25 years old at the time of study registration

• Histologically confirmed disease in one of the following four groups:

  • Group 1 - Acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML)
  • Group 2 - Neuroblastoma Group 3 - Sarcoma
  • Group 4 - High grade glioma (as defined by 2016 WHO CNS classification)

• Radiological or laboratory evidence of disease progression (during or after completion of first line treatment) or any subsequent recurrence (biopsy at relapse is not mandated).

• Measurable bone marrow disease (group 1) or at least one evaluable radiological site of disease (group 2, 3 and 4).

• Adequate liver function defined as a total bilirubin ≤1.5x the upper limit of normal for age and ALT ≤ 3x the upper limit of normal for age

• Documented negative pregnancy test for female patients of childbearing potential within 7 days of trial entry

• Sexually active patients must agree to use adequate and appropriate contraception while on study drug and for 12 months following treatment discontinuation

• Written informed consent given by patient and/or parents/legal representative

Exclusion Criteria:

• Previous treatment with another therapeutic arginine depleting drug (bacterial or human) or arginase inhibitor
• Presence of any ≥ CTCAE grade 3 clinically significant treatment-related toxicity from prior therapies
• Pregnant or lactating female
• Evidence of uncontrolled infection