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
- Conditions
- onbehandelbare en/of terugkerende vorm van kanker: leukemie, hoogradig glioom, neuroblastoom, sarcoomrelapsed or refractory cancer10027655
- Registration Number
- NL-OMON49172
- Lead Sponsor
- Cancer Research UK Clinical Trials Unit
- Brief Summary
Trial is onging in other countries
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 4
Inclusion Criteria
* Aged 1- <25 years old at the time of study registration
* Histologically confirmed disease in one of the following four groups:
o Group 1 - Acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia
(AML)
o Group 2 - Neuroblastoma
o Group 3 - Sarcoma
o 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 (see section 5.3 for details)
* Written informed consent given by patient and/or parents/legal
representative*
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Phase I: the safe and optimal (in terms of arginine depletion) RP2D of BCT-100<br /><br>as determined by:<br /><br>oSafety profile as measured by the occurrence/non-occurrence of DLT within 28<br /><br>daysof treatment with BCT-100. DLTs are defined in section 3.1.2.<br /><br>oOptimal dose as measured by the complete depletion of arginine. This is<br /><br>defined asAAD <8µM arginine in the blood after 4 doses of BCT-100.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Phase II: disease response (Complete Response (CR) or Partial Response (PR))<br /><br>after 8 weeks oftreatment with BCT-100 as defined by:<br /><br>oGroup 1 (Leukaemia): CR, Complete response with incomplete count recovery<br /><br>(CRi),Complete response without platelet recovery (CRp; ALL only), or PR<br /><br>determined bybone marrow, peripheral blood count/blasts and extramedullary<br /><br>disease.(seeAppendix 4 for details; AML criteria based on Cheson et al 2003)<br /><br>oGroup 2 (Neuroblastoma): CR/PR determined by cross-sectional imaging by CT<br /><br>orMRI, MIBG scan and bone marrow evaluation using the International<br /><br>NeuroblastomaResponse Criteria (INRC) (Appendix 7).<br /><br>oGroup 3 (Sarcoma): CR/PR determined by cross-sectional imaging by CT or<br /><br>MRIusing RECIST version 1.1 (Appendix 5).<br /><br>oGroup 4 (High grade glioma): CR/PR determined by cross-sectional imaging by<br /><br>MRIusing RANO criteria (Appendix 6).</p><br>