Clinical trial NCT05532722: ABC008 in Subjects with T-cell Large Granular Lymphocytic Leukemia (T-LGLL)
Official title: A Study of ABC008 in Subjects with T-cell Large Granular Lymphocytic Leukemia (T-LGLL)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: T-cell Large Granular Lymphocytic Leukemia
Keywords: T-cell Large Granular Lymphocytic Leukemia
T-LGLL
Lead sponsor: Abcuro, Inc.
Sponsor class: INDUSTRY
First posted: 2022-09-08
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: An open label, ascending dose study for adult subjects with T-cell Large Granular Lymphocytic Leukemia (T-LGLL)


Eligibility criteria: Inclusion Criteria:

* Is at least 18 years of age.
* Has body mass index (BMI) ≤35 kg/m2.
* Has a documented diagnosis of T LGLL.
* Has any 1 or more of the following at Screening:

  * Absolute neutrophil count (ANC) \<0.5 x 109/L
  * ANC ≥0.5 x 109/L and \<1.0 x 109/L associated with recurrent infection (≥2 or more infections requiring antimicrobial therapy within the previous 12 months)
  * Hemoglobin (Hgb) \<8 g/dL or packed red blood cell transfusion frequency ≥1 time in the 4 weeks immediately prior to Screening
  * Hgb ≥8 g/dL and \<10 g/dL accompanied by documented symptoms of anemia, e.g., fatigue, weakness, pale or yellowish skin, irregular heartbeat, shortness of breath, dizziness, or lightheadedness.
* Has adequate hepatic and renal function at Screening, as indicated by:

  * Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST); \<2.5x the upper limit of normal (ULN)
  * Total bilirubin ≤1.5 ULN; subjects with Gilbert syndrome must have a total bilirubin \<3.0x ULN with direct bilirubin \<1.0x ULN at time of Screening
  * Estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) equation corrected for the body surface area of the subject calculated by the Mosteller equation and divided by 1.73
* Agrees to adhere to the current Centers for Disease Control advice regarding minimizing exposure to severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) from the first Screening Visit until the End of Study (EOS)/Early Termination Visit (ETV).

Exclusion Criteria:

* Has reactive large granular lymphocytosis.
* Has active anemia secondary to confirmed etiologies other than T-LGLL, including known vitamin or mineral deficiency, gastrointestinal bleeding, or genetic disorder; or has active neutropenia secondary to known vitamin or mineral deficiencies or genetic disorder.
* Has a platelet count ≤20 x 109/L or other clinically significantly abnormal laboratory results not related to the underlying condition in the Investigator's or Sponsor's opinion at Screening.
* Has known hypersensitivity to any component of the formulation of ABC008, or history of anaphylaxis to any prior mAb therapy.
* Has any other autoimmune or autoinflammatory disease other than RA, inclusion body myositis (IBM), secondary Sjogren's syndrome (SS), or thyroid disease.
* Has another myelo /lympho proliferative disorder or malignancy (other than monoclonal gammopathy of unknown significance \[MGUS\] not requiring treatment) within the past 5 years prior to Screening except completely resected nonmelanoma skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ at any site.
* Has a current diagnosis of active tuberculosis (TB)
* Has a history of herpes zoster infection that was disseminated, required hospitalization, or IV antiviral therapy in the 24 weeks prior to Day 1.
* Active, chronic, or past history of hepatitis B virus or hepatitis C virus (HCV) infection (hepatitis B core antibody or surface antigen positive, or HCV antibody positive with reflex HCV ribonucleic acid \[RNA\] positive at Screening; individuals who have received curative therapy for HCV are permitted if therapy was completed at least 24 weeks prior to Screening and subject is HCV RNA negative);
* Has known active bacterial, viral, fungal, or atypical mycobacterial infection, or any major episode of infection that required hospitalization
* Has received live (including attenuated) vaccination in the 30 days prior to Day 1 or killed vaccine within 14 days prior to Day 1.
* Is human immunodeficiency virus (HIV) positive by antigen/antibody test, human T cell lymphotropic virus (HTLV 1 or 2) positive by antibody test.
* Has had major surgery (defined as surgery requiring general or regional anesthesia) within 6 weeks prior to Day 1 or is expected to receive surgery during the study.
* Has a history of organ transplant (e.g., solid, bone marrow) or is expected to receive one during the study.
* Has any other condition or social situations that would interfere with the subject's study participation, increase the risk associated with study participation or investigational product administration, interfere with the interpretation of study results, or would otherwise make the subject inappropriate for entry into this study in the Investigator's or Sponsor's opinion.

Primary outcomes:
measure: Incidence, nature, and severity of treatment-emergent AEs and SAEs as determined by NCI CTCAE v5.0
timeFrame: Through Study Completion an average of 48 weeks
Secondary outcomes:
measure: Change from baseline in safety lab (Hematology)
timeFrame: Through Study Completion an average of 48 weeks
measure: Change from baseline in safety lab (Chemistry)
timeFrame: Through Study Completion an average of 48 weeks
measure: Change from baseline in safety lab (Coagulation)
timeFrame: Through Study Completion an average of 48 weeks
measure: Change from baseline in safety lab (Complement)
timeFrame: Through Study Completion an average of 48 weeks
measure: Change from baseline in safety lab (Cytokines)
timeFrame: Through Study Completion an average of 48 weeks
measure: Change from baseline in safety lab (CMV Viral Load)
timeFrame: Through Study Completion an average of 48 weeks
measure: Change from baseline in safety lab (EBV Viral Load)
timeFrame: Through Study Completion an average of 48 weeks
measure: Change from baseline in ECG (Rhythm)
timeFrame: Through Study Completion an average of 48 weeks
measure: Change from baseline in ECG (Heart Rate)
timeFrame: Through Study Completion an average of 48 weeks
measure: Change from baseline in ECG parameters
timeFrame: Through Study Completion an average of 48 weeks
measure: Change from baseline in vital sign (Systolic and diastolic blood pressure)
timeFrame: Through Study Completion an average of 48 weeks
measure: Change from baseline in vital sign (temperature)
timeFrame: Through Study Completion an average of 48 weeks
measure: Change from baseline in vital sign (respiratory rate)
timeFrame: Through Study Completion an average of 48 weeks
measure: Change from baseline in vital sign (pulse rate)
timeFrame: Through Study Completion an average of 48 weeks
measure: Percentage of subjects demonstrating overall response (defined as total number of subjects with CR or PR) at all time points assessed
timeFrame: Day 1 and throughout the 48 weeks of follow up
measure: Percentage of subjects demonstrating complete response at all time points assessed
timeFrame: Day 1 and throughout the 48 weeks of follow up
measure: Percentage of subjects demonstrating partial response at all time points assessed
timeFrame: Day 1 and throughout the 48 weeks of follow up
measure: Duration of response at all time points assessed
timeFrame: Day 1 and throughout the 48 weeks of follow up
measure: Overall survival at Week 48
timeFrame: Day 1 and throughout the 48 weeks of follow up
measure: The change from baseline in levels of KLRG1 expressing lymphocytes over time
timeFrame: Day 1 and throughout the 48 weeks of follow up
measure: The change from baseline in levels of T-LGL counts over time
timeFrame: Day 1 and throughout the 48 weeks of follow up
measure: The change from baseline in levels of lymphocyte subsets over time
timeFrame: Day 1 and throughout the 48 weeks of follow up
measure: The maximum serum concentration [CMax] of ABC008
timeFrame: Day 1 and throughout the 48 weeks of follow up
measure: The time to maximum concentration [TMax] of ABC008
timeFrame: Day 1 and throughout the 48 weeks of follow up
measure: The area under the concentration-time curve [AUC] of ABC008
timeFrame: Day 1 and throughout the 48 weeks of follow up
measure: The apparent clearance [CL/F] of ABC008
timeFrame: Day 1 and throughout the 48 weeks of follow up
measure: The apparent volume of distribution [Vd/F] of ABC008
timeFrame: Day 1 and throughout the 48 weeks of follow up
measure: The elimination half-life [t½] of ABC008
timeFrame: Day 1 and throughout the 48 weeks of follow up
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Houston
country: United States
facility: The University of Texas M.D. Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute, University of Utah
state: Utah
Study officials:
References: