Clinical trial NCT03239392: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: LGL Leukemia
CTCL
Keywords: BNZ-1
Cytokine
IL-2
IL-15
Lead sponsor: Bioniz Therapeutics
Sponsor class: INDUSTRY
First posted: 2017-08-04
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Incidence, severity and relationship of treatment-emergent adverse events
timeFrame: 1 month
measure: Incidence, severity and relationship of treatment-emergent adverse events
timeFrame: 4 months
Secondary outcomes:
measure: Pharmacodynamics
timeFrame: 16 weeks
measure: Single-dose and steady-state Cmax
timeFrame: 16 weeks
measure: Single-dose and steady-state AUC
timeFrame: 16 weeks
measure: Steady-state Elimination half-life (t1/2)
timeFrame: 16 weeks
Other outcomes:
measure: Exploratory assessment of changes from baseline in CTCL disease severity (mSWAT)
timeFrame: 16 weeks
measure: Exploratory assessment of Complete Response in LGL
timeFrame: 16 weeks
measure: Exploratory assessment of Partial Response in LGL
timeFrame: 16 weeks
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Columbus
country: United States
facility: The James Cancer Center, Ohio State University
state: Ohio
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
Study officials:
affiliation: Ohio State University
name: Jonathan Brammer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: