A Pilot Study 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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- safety of PEG-BCT-100 in patients with relapsed or refractory leukemia or lymphoma receiving PEG-BCT-100 [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
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)
- 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 ] [ Designated as safety issue: No ]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. [ Time Frame: 1st dose: 1, 72, 168 hrs post dose; 2nd-4th dose: 1, 168 hrs post dose ] [ Designated as safety issue: No ]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. [ 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 ] [ Designated as safety issue: No ]
- 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 [ Time Frame: 1 year ] [ Designated as safety issue: No ]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
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||August 2013|
|Estimated Primary Completion Date:||February 2013 (Final data collection date for primary outcome measure)|
Drug: Recombinant human arginase 1 Peg5000
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.
Other Name: PEG-BCT-100, rhArg1peg5000
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.
|Department of Paediatrics and Adolescent Medicine, The University of Hong Kong||Recruiting|
|Hong Kong, China|
|Contact: Amanda MOK 852-22554480 firstname.lastname@example.org|
|Principal Investigator: Alan K Chiang, Dr.|
|Principal Investigator:||Alan K Chiang, Dr.||Department of Paediatrics and Adolescent Medicine, The University of Hong Kong|