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Efficacy and Safety Study of Recombinant Human Arginase 1 in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Primary Purpose

Acute Myeloid Leukemia

Status

Unknown status

Phase

Phase 2

Locations

Hong Kong

Study Type

Interventional

Intervention

PEG-BCT-100

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Acute myeloid leukemia, AML, pegylated recombinant human arginase, PEG-BCT-100

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Adult patients ≥18 year-old at the time of informed consent
Documented relapsed or refractory AML after at least two standard chemotherapy regimen or in whom the treating physicians considered unfit for further chemotherapy treatment
The Eastern Cooperative Oncology Group (ECOG) performance status equal or less than 2
Patients from whom valid consent is obtained

Exclusion Criteria:

Patients who have received any induction chemotherapy, investigational treatment and arginine depleting agent within 2 weeks prior to the start of the PEG-BCT-100 (not including hydroxyurea or thioguanine)
Any toxic effects (except hair loss) of the prior therapy have not been resolved to Grade 1 or less according to National Cancer Institute Common Terminology Criteria for Adverse Events
Total bilirubin > 1.5 x Upper Limit of Normal (ULN) not related to haemolysis or Gilbert's disease, and ratio of concentrations of aspartate transaminase and alanine transaminase (AST/ALT) > 5 x ULN
Creatinine > 2 x ULN or estimated glomerular filtration rate using Modification of Diet in Renal Disease formula < 60 ml/min/1.73 m2
Second active malignancy within the past year except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
Uncontrolled concomitant illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia
History of HIV-1 seropositivity
Active infection not adequately responding to appropriate therapy
Patient is pregnant or lactating
Female with childbearing potential who is not willing to use contraceptive methods which, in the opinion of the investigator, are effective and adequate while on study treatment and for 6 months after the last dose of study treatment
Male with a female partner with childbearing potential who is not willing to use contraceptive methods which, in the opinion of the investigator, are effective and adequate while on study treatment and for 6 months after the last dose of study treatment
Any condition that is unstable or can jeopardize the safety of the patients and their compliance to the study

Sites / Locations

The University of Hong Kong, Queen Mary Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PEG-BCT-100

Arm Description

PEG-BCT-100 (PEGylated recombinant human arginase)

Outcomes

Primary Outcome Measures

Complete remission (CR) rate

Secondary Outcome Measures

Overall response rate (ORR)

proportion of patients achieving CR or CRi or partial remission (PR)

Duration of remission

Time to progression (TTP)

Progression-free survival (PFS)

Overall survival (OS)

AE and SAE

Incidence of AE and SAE by severity grading as assessed according to CTCAE v4.03

PK - Area under the plasma concentration versus time curve (AUC)

PK - Peak plasma concentration of PEG-BCT-100 after administration (Cmax)

PK - Lowest concentration that PEG-BCT-100 reaches before the next dose is administered (Cmin)

PK - clearance

PK - volume of distribution

PK - elimination half-life

arginine depletion

PK/PD relationship

dose response

Anti-drug antibody (ADA)

amount of ADA in patient sample (ng/mL)

neutralizing anti-drug antibody (nADA)

amount of nADA in patient sample (ng/mL)

Full Information

NCT ID

NCT02899286

First Posted

September 6, 2016

Last Updated

July 27, 2017

Sponsor

Bio-Cancer Treatment International Limited

1. Study Identification

Unique Protocol Identification Number

NCT02899286

Brief Title

Efficacy and Safety Study of Recombinant Human Arginase 1 in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Official Title

A Phase II Open-label Study of the Efficacy and Safety of Recombinant Human Arginase 1 (PEG-BCT-100) in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Study Type

Interventional

2. Study Status

Record Verification Date

July 2017

Overall Recruitment Status

Unknown status

Study Start Date

September 2016 (undefined)

Primary Completion Date

September 2019 (Anticipated)

Study Completion Date

March 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bio-Cancer Treatment International Limited

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

To evaluate the efficacy of PEG-BCT-100 in patients with relapsed or refractory acute myeloid leukemia (AML) in terms of remission rate.

Detailed Description

This is a phase 2, non-randomised, open-label study that aims at evaluating the efficacy of single agent PEG-BCT-100 in adult patients with relapsed/refractory AML. Eligible patients will receive intravenous (IV) infusion of PEG-BCT-100 weekly until disease progression, unacceptable drug-related toxicity(ies), allogeneic haematopoietic stem cell transplantation or withdrawal of subject consent. Pharmacokinetic (PK) of PEG-BCT-100 and pharmacodynamics (PD) activity of PEG-BCT-100 on arginine depletion will be evaluated throughout the study. Plasma arginine level, intracellular blast arginine level (IBAL) in peripheral blood (PB) and bone marrow (BM) will be measured at specific time points. PEG-BCT-100 will be given once weekly at 1600 Units/kg (2.7mg/kg) per dose for three weeks (Cycle 1). If the post-treatment IBAL-BM examined within 5 days prior to each cycle fails to drop at least 70% from baseline value and disease response fails to achieve complete remission (CR) or complete remission with incomplete blood count recovery (CRi), PEG-BCT-100 may be increased to 2500 U/kg (the maximum tolerated dose as reported previously) at investigator's discretion. Disease response will be assessed within 5 days prior to each cycle according to the International Working Group (IWG) AML Response Criteria. Safety and toxicity will be assessed through physical examinations, vital signs, blood tests and urinalysis throughout the study. Adverse event (AE) and serious adverse events (SAE) will be reported according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.03 (CTCAE v4.03) until 28 days after the last dose of PEG-BCT-100. Immunogenicity response including anti-drug antibody (ADA) level and neutralizing antibody level will be assessed weekly for the first 2 cycles of PEG-BCT-100, pre-dose of each cycle thereafter and End of Study (EoS). Specific response predictive biomarkers in circulating and BM blasts, and emerging genetic markers will also be explored in the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Myeloid Leukemia

Keywords

Acute myeloid leukemia, AML, pegylated recombinant human arginase, PEG-BCT-100

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

PEG-BCT-100

Arm Type

Experimental

Arm Description

PEG-BCT-100 (PEGylated recombinant human arginase)

Intervention Type

Biological

Intervention Name(s)

PEG-BCT-100

Intervention Description

PEGylated recombinant human arginase

Primary Outcome Measure Information:

Title

Complete remission (CR) rate

Time Frame

3 years

Secondary Outcome Measure Information:

Title

Overall response rate (ORR)

Description

proportion of patients achieving CR or CRi or partial remission (PR)

Time Frame

3 years

Title

Duration of remission

Time Frame

3 years

Title

Time to progression (TTP)

Time Frame

3 years

Title

Progression-free survival (PFS)

Time Frame

3 years

Title

Overall survival (OS)

Time Frame

3 years

Title

AE and SAE

Description

Incidence of AE and SAE by severity grading as assessed according to CTCAE v4.03

Time Frame

3 years

Title

PK - Area under the plasma concentration versus time curve (AUC)

Time Frame

2 years

Title

PK - Peak plasma concentration of PEG-BCT-100 after administration (Cmax)

Time Frame

2 years

Title

PK - Lowest concentration that PEG-BCT-100 reaches before the next dose is administered (Cmin)

Time Frame

2 years

Title

PK - clearance

Time Frame

2 years

Title

PK - volume of distribution

Time Frame

2 years

Title

PK - elimination half-life

Time Frame

2 years

Title

Description

arginine depletion

Time Frame

2 years

Title

PK/PD relationship

Description

dose response

Time Frame

2 years

Title

Anti-drug antibody (ADA)

Description

amount of ADA in patient sample (ng/mL)

Time Frame

2 years

Title

neutralizing anti-drug antibody (nADA)

Description

amount of nADA in patient sample (ng/mL)

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Adult patients ≥18 year-old at the time of informed consent Documented relapsed or refractory AML after at least two standard chemotherapy regimen or in whom the treating physicians considered unfit for further chemotherapy treatment The Eastern Cooperative Oncology Group (ECOG) performance status equal or less than 2 Patients from whom valid consent is obtained Exclusion Criteria: Patients who have received any induction chemotherapy, investigational treatment and arginine depleting agent within 2 weeks prior to the start of the PEG-BCT-100 (not including hydroxyurea or thioguanine) Any toxic effects (except hair loss) of the prior therapy have not been resolved to Grade 1 or less according to National Cancer Institute Common Terminology Criteria for Adverse Events Total bilirubin > 1.5 x Upper Limit of Normal (ULN) not related to haemolysis or Gilbert's disease, and ratio of concentrations of aspartate transaminase and alanine transaminase (AST/ALT) > 5 x ULN Creatinine > 2 x ULN or estimated glomerular filtration rate using Modification of Diet in Renal Disease formula < 60 ml/min/1.73 m2 Second active malignancy within the past year except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast Uncontrolled concomitant illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia History of HIV-1 seropositivity Active infection not adequately responding to appropriate therapy Patient is pregnant or lactating Female with childbearing potential who is not willing to use contraceptive methods which, in the opinion of the investigator, are effective and adequate while on study treatment and for 6 months after the last dose of study treatment Male with a female partner with childbearing potential who is not willing to use contraceptive methods which, in the opinion of the investigator, are effective and adequate while on study treatment and for 6 months after the last dose of study treatment Any condition that is unstable or can jeopardize the safety of the patients and their compliance to the study

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Anskar Leung

Organizational Affiliation

The University of Hong Kong

Official's Role

Principal Investigator

Facility Information:

Facility Name

The University of Hong Kong, Queen Mary Hospital

City

Hong Kong

Country

Hong Kong

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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Efficacy and Safety Study of Recombinant Human Arginase 1 in Patients With Relapsed or Refractory Acute Myeloid Leukemia

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