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

NCT03455140 | Completed Phase 1 DMC

• 1 other identifier: RG_16-040
• Study Type: interventional
• Target: 49
• Locations: 3 countries
• Sites: 14

Brief Summary

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.

Conditions

Cancer; Pediatric Solid Tumor; Pediatric AML; Pediatric ALL

Keywords

Arginine; Arginase; Children; Young Adult

Outcome Measures

Primary Outcomes (2)

• Phase I: to establish the recommended phase II dose (RP2D) of BCT-100 in children and young adults as assessed by dose limiting toxicity (DLT) and complete arginine depletion

  Safety profile as measured by the occurrence/non-occurrence of DLT within 28 days of treatment with BCT-100. o Optimal dose as measured by the complete depletion of arginine. This is defined as AAD \<8μM arginine in the blood after 3 doses of BCT-100.

  28 days

• Phase II: to determine the activity of single agent BCT-100 against relapsed/refractory leukaemia, neuroblastoma, sarcoma and high grade glioma in children and young adults as measured by disease response after 8 weeks.

  Disease response (Complete Response (CR) or Partial Response (PR)) after 8 weeks of treatment with BCT-100

  After 8 weeks

Secondary Outcomes (14)

• The incidence and severity of Adverse Events (AEs) as Assessed by CTCAE v4

  28 days after treatment completion

• Disease response - Leukaemia

  Within 1 year

• Disease response - Sarcoma

  Within 1 year

• Disease response - High Grade Glioma

  Within 1 year

• Disease response - Neuroblastoma

  Within 1 year

Study Arms (4)

Group 1 - Leukaemia

EXPERIMENTAL

PEG- BCT-100 in patients with Leukaemia Starting dose 1600U/Kg IV infusion weekly

Drug: PEG- BCT-100

Group 2 - Neuroblastoma

EXPERIMENTAL

PEG- BCT-100 in patients with Neuroblastoma Starting dose 1600U/Kg IV infusion weekly

Drug: PEG- BCT-100

Group 3 - Sarcomas

EXPERIMENTAL

PEG- BCT-100 in patients with Sarcomas Starting dose 1600U/Kg IV infusion weekly

Drug: PEG- BCT-100

Group 4 - High Grade Glioma

EXPERIMENTAL

PEG- BCT-100 in patients with High Grade Gliomas Starting dose 1600U/Kg IV infusion weekly

Drug: PEG- BCT-100

Interventions

PEG- BCT-100 DRUG

PEGylated recombinant human arginase 1

Also known as: rhArg1peg5000

Group 1 - Leukaemia; Group 2 - Neuroblastoma; Group 3 - Sarcomas; Group 4 - High Grade Glioma

Eligibility Criteria

• Age: 1 Year - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Birmingham: lead

Study Sites (14)

Women's & Children's Hospital

Adelaide, Australia

Location

Queensland Children's Hospital

Brisbane, Australia

Location

Royal Children's Hospital Melbourne

Melbourne, Australia

Location

Perth Children's Hospital

Perth, Australia

Location

Children's Hospital Westmead

Sydney, Australia

Location

Sydney Children's Hospital

Sydney, Australia

Location

Princes Maxima Centrum

Utrecht, Netherlands

Location

Birmingham Children's Hospital

Birmingham, United Kingdom

Location

Bristol Royal Hospital for Children

Bristol, United Kingdom

Location

Addenbrookes Hospital

Cambridge, United Kingdom

Location

Royal Hospital for Children

Glasgow, United Kingdom

Location

Leeds Children's Hospital

Leeds, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, United Kingdom

Location

Royal Marsden Hospital

Sutton, United Kingdom

Location

Related Publications (1)

• Fenwick N, Weston R, Wheatley K, Hodgson J, Marshall L, Elliott M, Makin G, Ng A, Brennan B, Lowis S, Adamski J, Kilday JP, Cox R, Gattens M, Moore A, Trahair T, Ronghe M, Campbell M, Campbell H, Williams MW, Kirby M, Van Eijkelenburg N, Keely J, Scarpa U, Stavrou V, Fultang L, Booth S, Cheng P, De Santo C, Mussai F. PARC: 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. Front Oncol. 2024 Jan 31;14:1296576. doi: 10.3389/fonc.2024.1296576. eCollection 2024.

  PMID: 38357205 DERIVED

MeSH Terms

Conditions

Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

BCT-100

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Francis J Mussai, DPhil

  University of Birmingham

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2018
• First Posted: March 6, 2018
• Study Start: August 28, 2018
• Primary Completion: July 22, 2022
• Study Completion: July 22, 2022
• Last Updated: September 2, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (6); GB (7); NL (1)