Siltuximab in Large Granular Lymphocytic Leukemia (LGLL)

NCT05316116 | Terminated Early Phase 1 DMC FDA Drug

• 1 other identifier: MCC-21035
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Large Granular Lymphocyte Leukemia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Complete Response Rate (CR)

  Up to 30 months

• Time to Response (TTR)

  Up to 30 months

• Duration of Response (DOR)

  Up to 30 months

• Duration of Complete Response

  Up to 30 months

• Time to Complete Response

  Up to 30 months

Study Arms (1)

Siltuximab

EXPERIMENTAL

Siltuximab will be given every 3 weeks, for between 18 and 36 weeks

Drug: Siltuximab

Interventions

Siltuximab DRUG

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).

Also known as: Interleukin-6

Siltuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• severe neutropenia less than 500/mm³, OR
• neutropenia associated with recurrent infection, OR
• symptomatic anemia with Hemoglobin \< 9 g/dL, OR
• transfusion-dependent anemia with transfusion needs \>= 1 u per month, OR
• severe thrombocytopenia \<20,000/mm³, OR
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• EUSA Pharma, Inc.: collaborator
• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trial Search

MeSH Terms

Conditions

Leukemia, Large Granular Lymphocytic

Interventions

siltuximab; Interleukin-6

Condition Hierarchy (Ancestors)

Leukemia, T-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Lubomir Sokol, MD, PhD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2022
• First Posted: April 7, 2022
• Study Start: February 15, 2023
• Primary Completion: October 18, 2024
• Study Completion: October 18, 2024
• Last Updated: February 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)