Back to resultsA Pilot Study of Recombinant Human Arginase 1 (rhArg1) in Patients With Relapsed or Refractory Leukemia or Lymphoma
Primary Purpose
Leukemia, Lymphoma
Status
Terminated
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Recombinant human arginase 1 Peg5000
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia
Eligibility Criteria
Inclusion Criteria:
- Male or female from 1 to 17 year-old, inclusive.
- Confirmed relapsed/refractory leukemia or lymphoma to the last regimen, and the patient is without standard therapy for the disease.
- For subjects aged <16 years, modified Lansky Play Performance Scale (Appendix A) of 40% or above; For subjects aged ≥16 years, Karnofsky Performance Status (Appendix B) of 40% or above.
- For lymphoma patients, at least one node or nodal mass is measurable by CT scan.
- Willing to adhere to the prohibitions and restrictions specified in this protocol.
- Subject's legally acceptable representative must has signed an informed consent document and patient aged 7 or above must provide an assenting signature on the informed consent document, indicating that he/she/they understand(s) the purpose of and procedures required for the study and is willing to participate in the study.
Exclusion Criteria:
- Has received cancer treatment, e.g. chemotherapy, targeted biologic or enzymes, either approved or investigational, within 2 weeks prior to the start of the PEG-BCT-100.
- Any toxic effects (except hair loss) of the prior therapy have not been resolved to Grade 2 or less according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events.
- Total bilirubin > 1.5 x ULN not related to hemolysis or Gilbert's disease, and AST/ALT > 5 x ULN
- Serum creatinine > 2 x ULN or calculated creatinine clearance < 60 ml/min.
- Any other active malignancy within the past year except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast.
- Uncontrolled intercurrent 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.
- Female patient is pregnant or lactating.
- Female patient with childbearing potential and sexual activity who does not agree or unable to use adequate contraceptive [including prescription oral contraceptives (birth control pills), contraceptive injections, intrauterine device (IUD), double-barrier method (spermicidal jelly or foam with condoms or diaphragm), contraceptive patch, or surgical sterilization] before entry and throughout the study.
- Male patient with sexual activity who does not agree to use adequate contraception (barrier method of birth control in conjunction with spermicidal jelly) prior to study entry and throughout the study.
- Use of any investigational drug(s) within 2 weeks prior to the start of the PEG-BCT-100.
- Use of any arginine depleting agent within 2 weeks prior to the start of the PEG-BCT-100.
- Subjects, who in the opinion of the Investigator, are unable to comply with the trial treatment and the related trial procedures.
Sites / Locations
- Department of Paediatrics and Adolescent Medicine, The University of Hong Kong
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Recombinant Human Arginase 1 Peg5000
Arm Description
Outcomes
Primary Outcome Measures
safety of PEG-BCT-100 in patients with relapsed or refractory leukemia or lymphoma receiving PEG-BCT-100
The primary endpoint is defined as the adverse event and serious adverse event related to the trial treatment. The adverse event includes unexpected clinical findings which could be related to the metabolic consequences of acute or prolong arginine depletion.
The following measures will be used to evaluate the safety of the trial treatment:
vital signs
laboratory tests of safety i.e. hematology, blood biochemistry, urinalysis
Adverse events (NCI CTC AE, version 4.0)
Secondary Outcome Measures
efficacy of PEG-BCT-100 in disease control in patients with leukemia or lymphoma who have received 4 doses PEG-BCT-100 1600 U/kg.
The percentage of patients who have disease controlled following the 4 doses of PEG-BCT-100 1600 U/kg. Disease control is defined by achieving complete remission (CR) or complete remission with incomplete blood count recovery (CRi) or partial remission (PR), or stable disease (SD).
pharmacokinetics (PK) profiles of PEG-BCT-100.
The subtracting baseline (SB) method will be used considering the endogenous background of arginase when estimating the PK parameters. The peak and trough concentrations will be listed for each dosing. The elimination rate and half life of rhArg1 will be estimated by the PK samplings during the postponement of trial treatment. The elimination rate will be assumed to be linear and estimated using the non-compartmental model. The individual steady state will be determined by visual inspection.
pharmacodynamics (PD) profiles in terms of plasma arginine in response to PEG-BCT-100.
The time to effective plasma arginine depletion defined as plasma arginine < 8uM for the first dose (500 U/kg);
The effectiveness of maintaining effective arginine depletion up to 8 days after multiple doses;
The concentration of plasma arginase during effective arginine depletion.
time to progression in leukemia or lymphoma patients receiving PEG-BCT-100
measured from date of first dose of PEG-BCT-100 until documention of disease pregression. Death due to cause other than progression will be censored. Patient without an event will be censored at date last known progression-free
Full Information
NCT ID
NCT01551628
First Posted
February 29, 2012
Last Updated
July 27, 2017
Sponsor
Bio-Cancer Treatment International Limited
Collaborators
The University of Hong Kong
1. Study Identification
Unique Protocol Identification Number
NCT01551628
Brief Title
A Pilot Study of Recombinant Human Arginase 1 (rhArg1) in Patients With Relapsed or Refractory Leukemia or Lymphoma
Official Title
A Pilot Study of the Safety and Preliminary Efficacy of Recombinant Human Arginase 1 (rhArg1) in Patients With Relapsed or Refractory Leukemia or Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2014
Overall Recruitment Status
Terminated
Why Stopped
slow patient recruitment
Study Start Date
April 2012 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
May 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bio-Cancer Treatment International Limited
Collaborators
The University of Hong Kong
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine whether Recombinant Human Arginase 1 (rhArg1)is safe and effective in the treatment of patients with Relapsed or Refractory Leukemia or Lymphoma.
Detailed Description
This is a pilot, open-label study of PEG-BCT-100 in patients with relapsed/refractory leukemia or lymphoma who have satisfied all inclusion/exclusion criteria.
Approximately 15 subjects will be enrolled or when 10 evaluable subjects are included in the study. Evaluable subjects are defined as subjects who have received 4 consecutive doses of PEG-BCT-100 1600U/kg within 6 weeks from the first 1600U/kg dose and completed the first disease response assessment.
After the initiation of trial treatment, safety parameters will be evaluated throughout the study. Adverse event (AE) will be graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.0 (NCI CTC AE v4). AE and serious AE (SAE) will be detected and recorded on the Case Report Forms (CRFs) until 15-28 days after the last dose of PEG-BCT-100.
Patients who achieve complete remission (CR)/complete remission with incomplete blood count recovery (CRi) following the 4 consecutive 1600U/kg doses may continue PEG-BCT-100 at the discretion of the investigator.
Patients who achieve partial remission (PR) or stable disease (SD) following the 4 consecutive 1600U/kg doses can continue treatment up to disease progression. Further continuation will be determined by the clinical judgment of the Investigator. Patients who have disease progression will be discontinued PEG-BCT-100.
Blood samples for PK and PD analysis will be collected and analyzed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Recombinant Human Arginase 1 Peg5000
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Recombinant human arginase 1 Peg5000
Other Intervention Name(s)
PEG-BCT-100, rhArg1peg5000
Intervention Description
Patients will receive weekly IV infusions of PEG-BCT-100, until evidence of disease progression, intolerable adverse events, or withdrawal of patient consent. For safety sake, each subject will receive an induction dose of PEG-BCT-100 500 U/kg and 1000 U/kg at week -2 and week -1, respectively. The study dose of PEG-BCT-100 1600 U/kg will be initiated at week 1 (Day1). Each escalation of dose level will be determined by the investigator according to each subject's tolerability and criteria for treatment discontinuation.
Primary Outcome Measure Information:
Title
safety of PEG-BCT-100 in patients with relapsed or refractory leukemia or lymphoma receiving PEG-BCT-100
Description
The primary endpoint is defined as the adverse event and serious adverse event related to the trial treatment. The adverse event includes unexpected clinical findings which could be related to the metabolic consequences of acute or prolong arginine depletion.
The following measures will be used to evaluate the safety of the trial treatment:
vital signs
laboratory tests of safety i.e. hematology, blood biochemistry, urinalysis
Adverse events (NCI CTC AE, version 4.0)
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
efficacy of PEG-BCT-100 in disease control in patients with leukemia or lymphoma who have received 4 doses PEG-BCT-100 1600 U/kg.
Description
The percentage of patients who have disease controlled following the 4 doses of PEG-BCT-100 1600 U/kg. Disease control is defined by achieving complete remission (CR) or complete remission with incomplete blood count recovery (CRi) or partial remission (PR), or stable disease (SD).
Time Frame
6 days after the first 4 doses of 1600 U/kg PEG-BCT-100
Title
pharmacokinetics (PK) profiles of PEG-BCT-100.
Description
The subtracting baseline (SB) method will be used considering the endogenous background of arginase when estimating the PK parameters. The peak and trough concentrations will be listed for each dosing. The elimination rate and half life of rhArg1 will be estimated by the PK samplings during the postponement of trial treatment. The elimination rate will be assumed to be linear and estimated using the non-compartmental model. The individual steady state will be determined by visual inspection.
Time Frame
1st dose: 1, 72, 168 hrs post dose; 2nd-4th dose: 1, 168 hrs post dose
Title
pharmacodynamics (PD) profiles in terms of plasma arginine in response to PEG-BCT-100.
Description
The time to effective plasma arginine depletion defined as plasma arginine < 8uM for the first dose (500 U/kg);
The effectiveness of maintaining effective arginine depletion up to 8 days after multiple doses;
The concentration of plasma arginase during effective arginine depletion.
Time Frame
predose; 1st induction: 1, 2, 4, 71, 168hrs post dose; 2nd induction: 2, 72, 168 hrs post dose; first dose: 1, 72, 168 hrs post dose; 2nd-4th dose: 168hrs post dose
Title
time to progression in leukemia or lymphoma patients receiving PEG-BCT-100
Description
measured from date of first dose of PEG-BCT-100 until documention of disease pregression. Death due to cause other than progression will be censored. Patient without an event will be censored at date last known progression-free
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female from 1 to 17 year-old, inclusive.
Confirmed relapsed/refractory leukemia or lymphoma to the last regimen, and the patient is without standard therapy for the disease.
For subjects aged <16 years, modified Lansky Play Performance Scale (Appendix A) of 40% or above; For subjects aged ≥16 years, Karnofsky Performance Status (Appendix B) of 40% or above.
For lymphoma patients, at least one node or nodal mass is measurable by CT scan.
Willing to adhere to the prohibitions and restrictions specified in this protocol.
Subject's legally acceptable representative must has signed an informed consent document and patient aged 7 or above must provide an assenting signature on the informed consent document, indicating that he/she/they understand(s) the purpose of and procedures required for the study and is willing to participate in the study.
Exclusion Criteria:
Has received cancer treatment, e.g. chemotherapy, targeted biologic or enzymes, either approved or investigational, within 2 weeks prior to the start of the PEG-BCT-100.
Any toxic effects (except hair loss) of the prior therapy have not been resolved to Grade 2 or less according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events.
Total bilirubin > 1.5 x ULN not related to hemolysis or Gilbert's disease, and AST/ALT > 5 x ULN
Serum creatinine > 2 x ULN or calculated creatinine clearance < 60 ml/min.
Any other active malignancy within the past year except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast.
Uncontrolled intercurrent 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.
Female patient is pregnant or lactating.
Female patient with childbearing potential and sexual activity who does not agree or unable to use adequate contraceptive [including prescription oral contraceptives (birth control pills), contraceptive injections, intrauterine device (IUD), double-barrier method (spermicidal jelly or foam with condoms or diaphragm), contraceptive patch, or surgical sterilization] before entry and throughout the study.
Male patient with sexual activity who does not agree to use adequate contraception (barrier method of birth control in conjunction with spermicidal jelly) prior to study entry and throughout the study.
Use of any investigational drug(s) within 2 weeks prior to the start of the PEG-BCT-100.
Use of any arginine depleting agent within 2 weeks prior to the start of the PEG-BCT-100.
Subjects, who in the opinion of the Investigator, are unable to comply with the trial treatment and the related trial procedures.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alan K Chiang, Dr.
Organizational Affiliation
Department of Paediatrics and Adolescent Medicine, The University of Hong Kong
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Paediatrics and Adolescent Medicine, The University of Hong Kong
City
Hong Kong
Country
China
12. IPD Sharing Statement
Links:
URL
http://www.hkuctc.com/index.php
Description
Clinical Trail Centre, The University of Hong Kong
URL
http://www.bio-cancer.com/
Description
Bio-Cancer Treatment International Limited
Learn more about this trial
A Pilot Study of Recombinant Human Arginase 1 (rhArg1) in Patients With Relapsed or Refractory Leukemia or Lymphoma
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