ABC008 in Subjects With T-cell Large Granular Lymphocytic Leukemia (T-LGLL)

T-cell Large Granular Lymphocytic Leukemia Clinical Trial

Official title:

A Study of ABC008 in Subjects With T-cell Large Granular Lymphocytic Leukemia (T-LGLL)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05532722
• Other study ID #: ABC008-LGL-101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 28, 2022
• Est. completion date: December 2025

Study information

• Verified date: May 2024
• Source: Abcuro, Inc.
• Contact: Michael McClain
• Phone: 617-865-5078
• Email: LGL-101_ClinicalTrial[@]abcuro.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• T-cell Large Granular Lymphocytic Leukemia

Intervention

Drug:
• ABC008
Given subcutaneous injection

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	City of Hope	Duarte	California
United States	The University of Texas M.D. Anderson Cancer Center	Houston	Texas
United States	University of Southern California	Los Angeles	California
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Huntsman Cancer Institute, University of Utah	Salt Lake City	Utah
United States	SUNY Upstate Medical University	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
Abcuro, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence, nature, and severity of treatment-emergent AEs and SAEs as determined by NCI CTCAE v5.0		Through Study Completion an average of 48 weeks
Secondary	Change from baseline in safety lab (Hematology)		Through Study Completion an average of 48 weeks
Secondary	Change from baseline in safety lab (Chemistry)		Through Study Completion an average of 48 weeks
Secondary	Change from baseline in safety lab (Coagulation)	Includes the following coagulation labs: INR and aPTT	Through Study Completion an average of 48 weeks
Secondary	Change from baseline in safety lab (Complement)	Includes the following complement labs: C3 and CH50	Through Study Completion an average of 48 weeks
Secondary	Change from baseline in safety lab (Cytokines)		Through Study Completion an average of 48 weeks
Secondary	Change from baseline in safety lab (CMV Viral Load)		Through Study Completion an average of 48 weeks
Secondary	Change from baseline in safety lab (EBV Viral Load)		Through Study Completion an average of 48 weeks
Secondary	Change from baseline in ECG (Rhythm)		Through Study Completion an average of 48 weeks
Secondary	Change from baseline in ECG (Heart Rate)		Through Study Completion an average of 48 weeks
Secondary	Change from baseline in ECG parameters	Includes the following ECG parameters: RR interval, PR interval, QRS interval, QT interval, QT interval corrected by Bazett's formula, and QTcF	Through Study Completion an average of 48 weeks
Secondary	Change from baseline in vital sign (Systolic and diastolic blood pressure)		Through Study Completion an average of 48 weeks
Secondary	Change from baseline in vital sign (temperature)		Through Study Completion an average of 48 weeks
Secondary	Change from baseline in vital sign (respiratory rate)		Through Study Completion an average of 48 weeks
Secondary	Change from baseline in vital sign (pulse rate)		Through Study Completion an average of 48 weeks
Secondary	Percentage of subjects demonstrating overall response (defined as total number of subjects with CR or PR) at all time points assessed		Day 1 and throughout the 48 weeks of follow up
Secondary	Percentage of subjects demonstrating complete response at all time points assessed	A complete response is defined by normalization of hemoglobin, neutrophil and platelet levels without transfusion	Day 1 and throughout the 48 weeks of follow up
Secondary	Percentage of subjects demonstrating partial response at all time points assessed	A partial response is defined by improvement in any of the following criteria but not all: hemoglobin, neutrophil and platelet levels without transfusion	Day 1 and throughout the 48 weeks of follow up
Secondary	Duration of response at all time points assessed		Day 1 and throughout the 48 weeks of follow up
Secondary	Overall survival at Week 48		Day 1 and throughout the 48 weeks of follow up
Secondary	The change from baseline in levels of KLRG1 expressing lymphocytes over time		Day 1 and throughout the 48 weeks of follow up
Secondary	The change from baseline in levels of T-LGL counts over time		Day 1 and throughout the 48 weeks of follow up
Secondary	The change from baseline in levels of lymphocyte subsets over time		Day 1 and throughout the 48 weeks of follow up
Secondary	The maximum serum concentration [CMax] of ABC008		Day 1 and throughout the 48 weeks of follow up
Secondary	The time to maximum concentration [TMax] of ABC008		Day 1 and throughout the 48 weeks of follow up
Secondary	The area under the concentration-time curve [AUC] of ABC008		Day 1 and throughout the 48 weeks of follow up
Secondary	The apparent clearance [CL/F] of ABC008		Day 1 and throughout the 48 weeks of follow up
Secondary	The apparent volume of distribution [Vd/F] of ABC008		Day 1 and throughout the 48 weeks of follow up
Secondary	The elimination half-life [t½] of ABC008		Day 1 and throughout the 48 weeks of follow up