A Pilot Study of Recombinant Human Arginase 1 (rhArg1) in Patients With Relapsed or Refractory Leukemia or Lymphoma

NCT01551628 | Terminated Phase 1 DMC

• 1 other identifier: BCT-100-003
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Leukemia; Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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: 1. vital signs 2. laboratory tests of safety i.e. hematology, blood biochemistry, urinalysis 3. Adverse events (NCI CTC AE, version 4.0)

  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.

  6 days after the first 4 doses of 1600 U/kg PEG-BCT-100

• pharmacokinetics (PK) profiles of PEG-BCT-100.

  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.

  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

  1 year

Study Arms (1)

Recombinant Human Arginase 1 Peg5000

EXPERIMENTAL

Drug: Recombinant human arginase 1 Peg5000

Interventions

Recombinant human arginase 1 Peg5000 DRUG

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.

Also known as: PEG-BCT-100, rhArg1peg5000

Recombinant Human Arginase 1 Peg5000

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bio-Cancer Treatment International Limited: lead
• The University of Hong Kong: collaborator

Study Sites (1)

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong

Hong Kong, China

Location

Related Links

• Clinical Trail Centre, The University of Hong Kong
• Bio-Cancer Treatment International Limited

MeSH Terms

Conditions

Leukemia; Lymphoma

Interventions

BCT-100

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Alan K Chiang, Dr.

  Department of Paediatrics and Adolescent Medicine, The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 29, 2012
• First Posted: March 13, 2012
• Study Start: April 1, 2012
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: July 31, 2017

Record last verified: 2014-03

Locations

CN (1)