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

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

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

Study Overview

• Status: Recruiting
• Conditions: T-cell Large Granular Lymphocytic Leukemia
• Intervention / Treatment: Drug: ABC008

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Michael McClain; Phone Number: 617-865-5078; Email: LGL-101_ClinicalTrial@abcuro.com

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope
      • Contact: Ryotaro Nakamura, M.D.; Phone Number: 877-467-3411
      • Principal Investigator: Ryotaro Nakamura, M.D.
    • Los Angeles, California, United States, 90033
      • Recruiting
      • University of Southern California
      • Contact: Christine Duran; Email: duran_c@med.usc.edu
      • Principal Investigator: Howard Liebman, M.D.
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Salvia Jain; Phone Number: 617-724-4000
      • Principal Investigator: Salvia Jain, M.D.
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute
      • Principal Investigator: Eric Jacobsen, M.D.
      • Contact: DFCI Clinical Trial Hotline; Phone Number: 877-338-7425
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
      • Contact: Erin Demakos; Phone Number: 212-241-5520; Email: erin.demakos@mssm.edu
      • Contact: Lewis Silverman, M.D.; Phone Number: 212 241-5520; Email: Lewis.Silverman@mssm.edu
      • Principal Investigator: Lewis Silverman, M.D.
    • Syracuse, New York, United States, 13210
      • Recruiting
      • SUNY Upstate Medical University
      • Contact: Patricia Benz; Phone Number: 315-464-8253; Email: benzp@upstate.edu
      • Principal Investigator: Bernard Poiesz, M.D.
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic Foundation
      • Contact: Moaath Mustafa Ali, M.D.; Phone Number: 866-223-8100; Email: taussigresearch@ccf.org
      • Principal Investigator: Moaath Mustafa Ali, M.D.
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas M.D. Anderson Cancer Center
      • Contact: Tapan Kadia, M.D.; Phone Number: 713-563-3435; Email: tkadia@mdanderson.org
      • Principal Investigator: Tapan Kadia, M.D.
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • Huntsman Cancer Institute, University of Utah
      • Contact: David L Samuel; Phone Number: 801-587-9834; Email: David.Samuel@hci.utah.edu
      • Principal Investigator: Paul J Shami, M.D.

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ABC008 Dose Level 1 Cohort; 0.25 mg / kg ABC008 Subjects receive ABC008 every 8 weeks. Cohorts receive escalating doses of ABC008 until completion of cohort 5 or any cohort is determined to have exceeded the maximum tolerated dose.	Drug: ABC008; Given subcutaneous injection
Experimental: ABC008 Dose Level 2 Cohort; 0.75 mg / kg ABC008 Subjects receive ABC008 every 8 weeks. Cohorts receive escalating doses of ABC008 until completion of cohort 5 or any cohort is determined to have exceeded the maximum tolerated dose.	Drug: ABC008; Given subcutaneous injection
Experimental: ABC008 Dose Level 3 Cohort; 1.5 mg / kg ABC008 Subjects receive ABC008 every 8 weeks. Cohorts receive escalating doses of ABC008 until completion of cohort 5 or any cohort is determined to have exceeded the maximum tolerated dose.	Drug: ABC008; Given subcutaneous injection
Experimental: ABC008 Dose Level 4 Cohort; 3.0 mg / kg ABC008 Subjects receive ABC008 every 8 weeks OR 1.5 mg / kg Subjects receive ABC008 every 4 weeks. Cohorts receive escalating doses of ABC008 until completion of cohort 5 or any cohort is determined to have exceeded the maximum tolerated dose.	Drug: ABC008; Given subcutaneous injection
Experimental: ABC008 Dose Level 5 Cohort; 3.0 mg / kg ABC008 Subjects receive ABC008 every 4 weeks. Cohorts receive escalating doses of ABC008 until completion of cohort 5 or any cohort is determined to have exceeded the maximum tolerated dose.	Drug: ABC008; Given subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in safety lab (Hematology)		Through Study Completion an average of 48 weeks
Change from baseline in safety lab (Chemistry)		Through Study Completion an average of 48 weeks
Change from baseline in safety lab (Coagulation)	Includes the following coagulation labs: INR and aPTT	Through Study Completion an average of 48 weeks
Change from baseline in safety lab (Complement)	Includes the following complement labs: C3 and CH50	Through Study Completion an average of 48 weeks
Change from baseline in safety lab (Cytokines)		Through Study Completion an average of 48 weeks
Change from baseline in safety lab (CMV Viral Load)		Through Study Completion an average of 48 weeks
Change from baseline in safety lab (EBV Viral Load)		Through Study Completion an average of 48 weeks
Change from baseline in ECG (Rhythm)		Through Study Completion an average of 48 weeks
Change from baseline in ECG (Heart Rate)		Through Study Completion an average of 48 weeks
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
Change from baseline in vital sign (Systolic and diastolic blood pressure)		Through Study Completion an average of 48 weeks
Change from baseline in vital sign (temperature)		Through Study Completion an average of 48 weeks
Change from baseline in vital sign (respiratory rate)		Through Study Completion an average of 48 weeks
Change from baseline in vital sign (pulse rate)		Through Study Completion an average of 48 weeks
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
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
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
Duration of response at all time points assessed		Day 1 and throughout the 48 weeks of follow up
Overall survival at Week 48		Day 1 and throughout the 48 weeks of follow up
The change from baseline in levels of KLRG1 expressing lymphocytes over time		Day 1 and throughout the 48 weeks of follow up
The change from baseline in levels of T-LGL counts over time		Day 1 and throughout the 48 weeks of follow up
The change from baseline in levels of lymphocyte subsets over time		Day 1 and throughout the 48 weeks of follow up
The maximum serum concentration [CMax] of ABC008		Day 1 and throughout the 48 weeks of follow up
The time to maximum concentration [TMax] of ABC008		Day 1 and throughout the 48 weeks of follow up
The area under the concentration-time curve [AUC] of ABC008		Day 1 and throughout the 48 weeks of follow up
The apparent clearance [CL/F] of ABC008		Day 1 and throughout the 48 weeks of follow up
The apparent volume of distribution [Vd/F] of ABC008		Day 1 and throughout the 48 weeks of follow up
The elimination half-life [t½] of ABC008		Day 1 and throughout the 48 weeks of follow up

Collaborators and Investigators

• Sponsor: Abcuro, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: August 19, 2022
• First Submitted That Met QC Criteria: September 6, 2022
• First Posted (Actual): September 8, 2022

Study Record Updates

• Last Update Posted (Estimated): December 6, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: T-cell Large Granular Lymphocytic Leukemia; T-LGLL
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, T-Cell; Leukemia; Leukemia, Lymphoid; Leukemia, Large Granular Lymphocytic
• Other Study ID Numbers: ABC008-LGL-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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