A Dose-Ranging Study of IV BNZ-1 in LGL Leukemia or Refractory CTCL
Primary Purpose
LGL Leukemia, CTCL
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
BNZ132-1-40
Sponsored by
About this trial
This is an interventional treatment trial for LGL Leukemia focused on measuring BNZ-1, Cytokine, IL-2, IL-15
Eligibility Criteria
Inclusion Criteria:
- Willing and able to consent and participate in the study.
- Agrees not to receive any other investigational product or therapy while participating in this study.
Must be:
- Currently using two forms of effective birth control (one of which is a barrier method) for the duration of the study for both males and females of childbearing potential. Effective methods of birth control include hormonal contraception (i.e., birth control pills, injected hormones, vaginal ring), intrauterine device, or barrier methods with spermicide (i.e., diaphragm with spermicide, condom with spermicide), or
- Surgically sterile (i.e., hysterectomy, tubal ligation, vasectomy).
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2.
- Life expectancy >1 year.
LGL-Specific:
Phenotypic studies (obtained within 8 weeks prior to study drug administration) from peripheral blood showing CD3+, CD57+ cells >400/mm³ or CD8+ cells >650/mm³.
- Note: Complete blood count (CBC) and differential should be reported for the phenotyped sample.
- Evidence for clonal T-cell receptor gene rearrangement (obtained within 1 year prior to study drug administration).
CTCL-Specific:
- Histopathologically confirmed mycosis fungoides or Sézary syndrome (CTCL stage IIB or greater according to the European Organization for Research and Treatment of Cancer/International Society for Cutaneous Lymphomas [EORTC-ISCL] consensus classification) at study entry with progressive, persistent, or recurrent disease who have no available remaining standard therapeutic options (i.e., Refractory) as determined by the Investigator.
Exclusion Criteria:
- Clinically relevant hepatic, neurological, pulmonary, ophthalmological, endocrine, renal, or other major systemic disease making implementation of the protocol or interpretation of the study results difficult, or that would put the subject at risk by participating in the study in the opinion of the Investigator.
- History of or currently active primary or secondary immunodeficiency.
- Known active bacterial, viral, fungal, mycobacterial infection, or other infection (including tuberculosis [TB] or atypical mycobacterial disease [but excluding fungal infection of nail beds, minor upper respiratory tract infection, and minor skin conditions]), or any major episode of infection that required hospitalization or treatment with IV antibiotics within 30 days of study drug administration or oral antibiotics within 14 days prior to study drug administration.
- Received other investigational products or therapy in the 60 days prior to study drug administration.
Sites / Locations
- City of Hope National Medical Center
- Moffitt Cancer Center
- The James Cancer Center, Ohio State University
- University of Virginia Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
BNZ-1
Arm Description
IV PEGylated BNZ132-1-40
Outcomes
Primary Outcome Measures
Incidence, severity and relationship of treatment-emergent adverse events
Incidence, severity and relationship of treatment-emergent adverse events
Secondary Outcome Measures
Pharmacodynamics
Flow cytometry: Change from baseline over time for Tregs, NK cells and CD8+ central memory T-cells
Single-dose and steady-state Cmax
Plasma levels of BNZ-1 will be measured after the 1st and last doses
Single-dose and steady-state AUC
Plasma levels of BNZ-1 will be measured after the 1st and last doses
Steady-state Elimination half-life (t1/2)
Plasma levels of BNZ-1 will be measured after the last dose
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03239392
Brief Title
A Dose-Ranging Study of IV BNZ-1 in LGL Leukemia or Refractory CTCL
Official Title
A Dose-Ranging Study of Intravenous BNZ132-1-40 in Patients With Large Granular Lymphocyte Leukemia or Refractory Cutaneous T-Cell Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
April 1, 2018 (Actual)
Primary Completion Date
June 30, 2020 (Actual)
Study Completion Date
June 30, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bioniz Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is an open-label, multi-center, dose-ranging study to characterize the safety, tolerability, preliminary efficacy, and PK/PD of up to four dose levels of BNZ-1 administered weekly by IV infusion to adults diagnosed with Large Granular Lymphocyte (LGL) Leukemia or refractory Cutaneous T-cell Lymphoma (CTCL).
Detailed Description
This study is an open-label, multi-center, dose-ranging study to characterize the safety, tolerability, preliminary efficacy, and PK/PD of up to four dose levels of BNZ-1 administered weekly by IV infusion to adults diagnosed with LGL or CTCL. The study has 5 periods:
Screening Period
4-week Treatment Period
3-month Treatment Extension Period
Long-term Extension Period (open-ended)
6-week Follow-up Period Subjects will be screened for eligibility within 30 days of study Day 1 (first dosing day of the 4-Week Treatment Period).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
LGL Leukemia, CTCL
Keywords
BNZ-1, Cytokine, IL-2, IL-15
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BNZ-1
Arm Type
Experimental
Arm Description
IV PEGylated BNZ132-1-40
Intervention Type
Drug
Intervention Name(s)
BNZ132-1-40
Other Intervention Name(s)
BNZ-1
Intervention Description
Injectable PEGylated peptide antagonist that binds to the common gamma chain (γc) signaling receptor for the cytokines interleukin (IL)-2, IL-9, and IL-15
Primary Outcome Measure Information:
Title
Incidence, severity and relationship of treatment-emergent adverse events
Time Frame
1 month
Title
Incidence, severity and relationship of treatment-emergent adverse events
Time Frame
4 months
Secondary Outcome Measure Information:
Title
Pharmacodynamics
Description
Flow cytometry: Change from baseline over time for Tregs, NK cells and CD8+ central memory T-cells
Time Frame
16 weeks
Title
Single-dose and steady-state Cmax
Description
Plasma levels of BNZ-1 will be measured after the 1st and last doses
Time Frame
16 weeks
Title
Single-dose and steady-state AUC
Description
Plasma levels of BNZ-1 will be measured after the 1st and last doses
Time Frame
16 weeks
Title
Steady-state Elimination half-life (t1/2)
Description
Plasma levels of BNZ-1 will be measured after the last dose
Time Frame
16 weeks
Other Pre-specified Outcome Measures:
Title
Exploratory assessment of changes from baseline in CTCL disease severity (mSWAT)
Description
mSWAT
Time Frame
16 weeks
Title
Exploratory assessment of Complete Response in LGL
Description
Normalization of CBC and LGL count
Time Frame
16 weeks
Title
Exploratory assessment of Partial Response in LGL
Description
ANC: >50% improvement from baseline and >500 cells/uL; or >50% reduction in transfusion requirements
Time Frame
16 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Willing and able to consent and participate in the study.
Agrees not to receive any other investigational product or therapy while participating in this study.
Must be:
Currently using two forms of effective birth control (one of which is a barrier method) for the duration of the study for both males and females of childbearing potential. Effective methods of birth control include hormonal contraception (i.e., birth control pills, injected hormones, vaginal ring), intrauterine device, or barrier methods with spermicide (i.e., diaphragm with spermicide, condom with spermicide), or
Surgically sterile (i.e., hysterectomy, tubal ligation, vasectomy).
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2.
Life expectancy >1 year.
LGL-Specific:
Phenotypic studies (obtained within 8 weeks prior to study drug administration) from peripheral blood showing CD3+, CD57+ cells >400/mm³ or CD8+ cells >650/mm³.
Note: Complete blood count (CBC) and differential should be reported for the phenotyped sample.
Evidence for clonal T-cell receptor gene rearrangement (obtained within 1 year prior to study drug administration).
CTCL-Specific:
Histopathologically confirmed mycosis fungoides or Sézary syndrome (CTCL stage IIB or greater according to the European Organization for Research and Treatment of Cancer/International Society for Cutaneous Lymphomas [EORTC-ISCL] consensus classification) at study entry with progressive, persistent, or recurrent disease who have no available remaining standard therapeutic options (i.e., Refractory) as determined by the Investigator.
Exclusion Criteria:
Clinically relevant hepatic, neurological, pulmonary, ophthalmological, endocrine, renal, or other major systemic disease making implementation of the protocol or interpretation of the study results difficult, or that would put the subject at risk by participating in the study in the opinion of the Investigator.
History of or currently active primary or secondary immunodeficiency.
Known active bacterial, viral, fungal, mycobacterial infection, or other infection (including tuberculosis [TB] or atypical mycobacterial disease [but excluding fungal infection of nail beds, minor upper respiratory tract infection, and minor skin conditions]), or any major episode of infection that required hospitalization or treatment with IV antibiotics within 30 days of study drug administration or oral antibiotics within 14 days prior to study drug administration.
Received other investigational products or therapy in the 60 days prior to study drug administration.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jonathan Brammer, MD, PhD
Organizational Affiliation
Ohio State University
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
10101
Country
United States
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
The James Cancer Center, Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
University of Virginia Cancer Center
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Time Frame
6 months after study data analysis is completed and a CSR has been generated
Learn more about this trial
A Dose-Ranging Study of IV BNZ-1 in LGL Leukemia or Refractory CTCL
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