Siltuximab in Large Granular Lymphocytic Leukemia (LGLL)

A Pilot Study of Siltuximab in Large Granular Lymphocytic Leukemia (LGLL)

The purpose of the study is to evaluate the safety and effectiveness of siltuximab for participants being treated for large granular lymphocytic leukemia (LGLL).

Study Overview

• Status: Terminated
• Conditions: Large Granular Lymphocyte Leukemia
• Intervention / Treatment: Drug: Siltuximab

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Male or female, aged >/= 18.
• Meet the diagnosis criteria of LGLL as below:
• a. For a patient with treatment-naive LGLL, peripheral blood needs to have CD3+ CD57+ cells >400/mm³ or CD8+ cells >650/mm³, and, evidence for clonal T cell receptor gamma or beta gene rearrangement by PCR needs to be detected in either peripheral blood or bone marrow.
• b. For patients with an established diagnosis of LGLL who have been previously treated, multicolor flow cytometry should identify a residual CD3+CD57+CD8+ LGLL population in peripheral blood or bone marrow, and, evidence for clonal T cell receptor gamma or beta gene rearrangement by PCR needs to be detected in either peripheral blood or bone marrow. There is no requirement that peripheral blood absolute clonal CD3+ CD57+ or CD8+ LGLL populations need to reach predetermined minimal value for eligibility since immunosuppressive therapy can significantly decrease LGLL cell count without any impact on neutropenia, anemia or thrombocytopenia which are major causes of morbidity and mortality

• Has at least one of the indications for treatment:

  1. severe neutropenia less than 500/mm³, OR
  2. neutropenia associated with recurrent infection, OR
  3. symptomatic anemia with Hemoglobin < 9 g/dL, OR
  4. transfusion-dependent anemia with transfusion needs >= 1 u per month, OR
  5. severe thrombocytopenia <20,000/mm³, OR
  6. thrombocytopenia <50,000/mm³ with bleeding.
• Participant can be treatment-naïve or previously treated for LGLL.
• Participant currently receiving therapy must have a wash-out period of ≥ 30 days or 5 elimination half-lives, whichever is longer, prior to study drug administration.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Creatinine clearance (CLCr) ≥15 mL/min.
• If a participant has chronic liver disease, Child-Pugh score needs to be either A or B.
• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to study drug infusion and agreement to use highly effective contraception during study participation and for an additional 3 months after the last dose of study drug.
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner during study participation and for an additional 3 months after the last dose of study drug. Men must agree to not donate sperm during the same period.

Exclusion Criteria:

• Any active infection requiring systemic therapy, including viral infections such as HIV, Hepatitis B, and/or Hepatitis C.
• Current use of methotrexate, cyclophosphamide, or cyclosporine for any medical conditions.
• Has coexisting myelodysplastic syndrome (MDS).
• Elevated LGL due to viral infection.
• Pregnancy or lactation.
• Known severe allergic reactions to siltuximab.
• At increased risk for Gastrointestinal (GI) perforation, in the opinion of the study investigator.
• Received live vaccine 30 days prior to study drug administration or Intend to receive live vaccine during treatment period and within 3 months after last dose of study drug.
• Rheumatological conditions such as rheumatoid arthritis (RA) are not exclusion criteria for the study.
• Coexisting hematological conditions such as autoimmune hematological anemia (AIHA) or immune thrombocytopenia (ITP) are not automatic exclusion criteria but will be at discretion of study investigator.
• Previous or concurrent malignancies not considered cured, except inactive non-melanoma skin cancer, in situ carcinoma of the cervix, early-stage prostate cancer, or other cancer deemed clinically insignificant by the Investigator.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the study Investigator.

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: Siltuximab; Siltuximab will be given every 3 weeks, for between 18 and 36 weeks	Drug: Siltuximab; Siltuximab will be given on day 1 of each cycle. The dose will be 11 mg/kg given over 1 hour by intravenous infusion. Each cycle is three weeks (+-3 days).; Other Names: Interleukin-6

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	Overall response rate is defined as the rate of achieving best response of CR or PR, and will be summarized for participants who have received any dose of study drug	Up to 30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rate (CR)	CR rate is defined as the percentage of patients achieving best response of CR.	Up to 30 months
Time to Response (TTR)	TTR is defined as time from first dose of study drug to time of meeting criteria for CR or PR, whichever comes first.	Up to 30 months
Duration of Response (DOR)	Duration of Response is defined as time from achieving either CR or PR, whichever comes first, to time of progression or starting another LGLL treatment, whichever comes first.	Up to 30 months
Duration of Complete Response	Duration of CR is defined as time from achieving CR to time of progression or starting another LGLL treatment, whichever comes first.	Up to 30 months
Time to Complete Response	Time to CR is defined as time from first dose of study drug to time of CR	Up to 30 months
Duration of Complete Response with Normalization of PB LGL Count	Rate of CR with normalization of PB LGL count is defined as meeting criteria for CR AND a normal PB LGL count ( <400/mm³ CD3+CD57+ cells or <650/mm³ CD8+ T cells in PB).	Up to 30 months
Progression Free Survival	PFS is defined as time from first dose of study drug to time of disease progression or starting another LGLL treatment, whichever comes first	Up to 30 months

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: EUSA Pharma, Inc.
• Investigators: Principal Investigator: Lubomir Sokol, MD, PhD, Moffitt Cancer Center

Publications and helpful links

Helpful Links

• Moffitt Cancer Center Clinical Trial Search

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2023
• Primary Completion (Actual): October 18, 2024
• Study Completion (Actual): October 18, 2024

Study Registration Dates

• First Submitted: March 30, 2022
• First Submitted That Met QC Criteria: March 30, 2022
• First Posted (Actual): April 7, 2022

Study Record Updates

• Last Update Posted (Actual): February 5, 2026
• Last Update Submitted That Met QC Criteria: February 3, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Leukemia, T-Cell; Hemic and Lymphatic Diseases; Leukemia, Large Granular Lymphocytic; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Intercellular Signaling Peptides and Proteins; Cytokines; Interleukins; siltuximab; Interleukin-6
• Other Study ID Numbers: MCC-21035

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes