LeukemiaPhase 1NCT01551628
A Pilot Study of Recombinant Human Arginase 1 (rhArg1) in Patients With Relapsed or Refractory Leukemia or Lymphoma
A Phase 1 study testing Recombinant human arginase 1 Peg5000 in people with Leukemia and Lymphoma, run by Bio-Cancer Treatment International Limited at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 17 years
- What is being tested?
- Recombinant human arginase 1 Peg5000
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteChina
- Study dates
- Apr 2012to May 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site
Department of Paediatrics and Adolescent Medicine, The University of Hong Kong
Hong Kong
About this study
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
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.
Read the 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.
- Being tested
- Recombinant human arginase 1 Peg5000
- Medical subject headings
- Leukemia, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant human arginase 1 Peg5000Drug
Also called PEG-BCT-100, rhArg1peg5000
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.
| Study group | Role | What they receive |
|---|---|---|
| Recombinant Human Arginase 1 Peg5000 | Experimental | Not described Receives: Drug: Recombinant human arginase 1 Peg5000 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 6 weeks
Secondary outcomes (4)
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).
Measured: 6 days after the first 4 doses of 1600 U/kg PEG-BCT-100
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.
Measured: 1st dose: 1, 72, 168 hrs post dose; 2nd-4th dose: 1, 168 hrs post dose
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.
Measured: 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
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
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2012 (estimated)
- Study startApr 2012
- Primary completionMay 2013
- Study completionMay 2013
Why it stopped: slow patient recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bio-Cancer Treatment International Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- The University of Hong Kong
- Responsible party
- Sponsor
- Investigators
- Alan K Chiang, Dr., Principal investigator, Department of Paediatrics and Adolescent Medicine, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01551628
- Sponsor's protocol ID
- BCT-100-003
- Status last verified
- Mar 2014
- First submitted
- 29 Feb 2012
- Last updated
- 31 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01551628
- Acronym / sponsor ID
- BCT-100-003
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow patient recruitment
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Bio-Cancer Treatment International LimitedIndustry (pharma, biotech, devices)
- Collaborators
- The University of Hong Kong
- Study start
- Apr 2012
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 13 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Recombinant Human Arginase 1 Peg5000 | Experimental | Drug: Recombinant human arginase 1 Peg5000 |
Who may qualify
- Ages
- 1 year to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Recombinant human arginase 1 Peg5000Also: PEG-BCT-100, rhArg1peg5000Patients 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. | Drug | Recombinant Human Arginase 1 Peg5000 |
Primary outcome
safety of PEG-BCT-100 in patients with relapsed or refractory leukemia or lymphoma receiving PEG-BCT-100
Time frame: 6 weeks
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: 1. vital signs 2. laboratory tests of safety i.e. hematology, blood biochemistry, urinalysis 3. Adverse events (NCI CTC AE, version 4.0)
4 secondary outcomes
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.
Time frame: 6 days after the first 4 doses of 1600 U/kg PEG-BCT-100
pharmacokinetics (PK) profiles of PEG-BCT-100.
Time frame: 1st dose: 1, 72, 168 hrs post dose; 2nd-4th dose: 1, 168 hrs post dose
pharmacodynamics (PD) profiles in terms of plasma arginine in response to PEG-BCT-100.
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
time to progression in leukemia or lymphoma patients receiving PEG-BCT-100
Time frame: 1 year
Results and safety
The study was stopped early (reason given: slow patient recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2017.
- Clinical Trail Centre, The University of Hong KongLink provided by the sponsor.
- Bio-Cancer Treatment International LimitedLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alan K Chiang, Dr. principal investigator
Department of Paediatrics and Adolescent Medicine, The University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Recombinant human arginase 1 Peg5000 in people with Leukemia and Lymphoma, run by Bio-Cancer Treatment International Limited at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 31 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: slow patient recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
safety of PEG-BCT-100 in patients with relapsed or refractory leukemia or lymphoma receiving PEG-BCT-100 (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2017.