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

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

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).

Study Overview

• Status: Completed
• Conditions: LGL Leukemia; CTCL
• Intervention / Treatment: Drug: BNZ132-1-40

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).

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 10101
      • City of Hope National Medical Center
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The James Cancer Center, Ohio State University
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

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

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: Bioniz Therapeutics
• Investigators: Principal Investigator: Jonathan Brammer, MD, PhD, Ohio State University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2018
• Primary Completion (Actual): June 30, 2020
• Study Completion (Actual): June 30, 2020

Study Registration Dates

• First Submitted: July 31, 2017
• First Submitted That Met QC Criteria: August 1, 2017
• First Posted (Actual): August 4, 2017

Study Record Updates

• Last Update Posted (Actual): May 25, 2021
• Last Update Submitted That Met QC Criteria: May 24, 2021
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Cytokine; IL-2; IL-15; BNZ-1
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia, T-Cell; Leukemia; Leukemia, Large Granular Lymphocytic
• Other Study ID Numbers: BNZ1-CT-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Time Frame: 6 months after study data analysis is completed and a CSR has been generated
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No