A Dose-Ranging Study of IV BNZ-1 in LGL Leukemia or Refractory CTCL

Sponsor

Bioniz Therapeutics (Industry)

Overall Status

Completed

CT.gov ID

NCT03239392

Collaborator

(none)

Enrollment

Locations

Arm

Actual Duration (Months)

12.5

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
LGL Leukemia CTCL	Drug: BNZ132-1-40	Phase 1/Phase 2

Detailed Description

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Dose-Ranging Study of Intravenous BNZ132-1-40 in Patients With Large Granular Lymphocyte Leukemia or Refractory Cutaneous T-Cell Lymphoma

Actual Study Start Date :

Apr 1, 2018

Actual Primary Completion Date :

Jun 30, 2020

Actual Study Completion Date :

Jun 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BNZ-1 IV PEGylated BNZ132-1-40	Drug: BNZ132-1-40 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 Other Names: BNZ-1

Arm

Intervention/Treatment

Experimental: BNZ-1

IV PEGylated BNZ132-1-40

Drug: BNZ132-1-40

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

Other Names:

BNZ-1

Outcome Measures

Primary Outcome Measures

Incidence, severity and relationship of treatment-emergent adverse events [1 month]
Incidence, severity and relationship of treatment-emergent adverse events [4 months]

Secondary Outcome Measures

Pharmacodynamics [16 weeks]
Flow cytometry: Change from baseline over time for Tregs, NK cells and CD8+ central memory T-cells
Single-dose and steady-state Cmax [16 weeks]
Plasma levels of BNZ-1 will be measured after the 1st and last doses
Single-dose and steady-state AUC [16 weeks]
Plasma levels of BNZ-1 will be measured after the 1st and last doses
Steady-state Elimination half-life (t1/2) [16 weeks]
Plasma levels of BNZ-1 will be measured after the last dose

Other Outcome Measures

Exploratory assessment of changes from baseline in CTCL disease severity (mSWAT) [16 weeks]
mSWAT
Exploratory assessment of Complete Response in LGL [16 weeks]
Normalization of CBC and LGL count
Exploratory assessment of Partial Response in LGL [16 weeks]
ANC: >50% improvement from baseline and >500 cells/uL; or >50% reduction in transfusion requirements

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center	Duarte	California	United States	10101
2	Moffitt Cancer Center	Tampa	Florida	United States	33612
3	The James Cancer Center, Ohio State University	Columbus	Ohio	United States	43210
4	University of Virginia Cancer Center	Charlottesville	Virginia	United States	22908