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Siltuximab in Large Granular Lymphocytic Leukemia (LGLL)

Primary Purpose

Large Granular Lymphocyte Leukemia

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Siltuximab
Sponsored by
H. Lee Moffitt Cancer Center and Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Large Granular Lymphocyte Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Moffitt Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Siltuximab

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Complete Response Rate (CR)
CR rate is defined as the percentage of patients achieving best response of CR.
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.
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.
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.
Time to Complete Response
Time to CR is defined as time from first dose of study drug to time of CR
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).
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

Full Information

First Posted
March 30, 2022
Last Updated
June 30, 2023
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
EUSA Pharma, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05316116
Brief Title
Siltuximab in Large Granular Lymphocytic Leukemia (LGLL)
Official Title
A Pilot Study of Siltuximab in Large Granular Lymphocytic Leukemia (LGLL)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 15, 2023 (Actual)
Primary Completion Date
September 1, 2025 (Anticipated)
Study Completion Date
September 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
EUSA Pharma, Inc.

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Large Granular Lymphocyte Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Siltuximab
Arm Type
Experimental
Arm Description
Siltuximab will be given every 3 weeks, for between 18 and 36 weeks
Intervention Type
Drug
Intervention Name(s)
Siltuximab
Other Intervention Name(s)
Interleukin-6
Intervention Description
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).
Primary Outcome Measure Information:
Title
Overall Response Rate
Description
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
Time Frame
Up to 30 months
Secondary Outcome Measure Information:
Title
Complete Response Rate (CR)
Description
CR rate is defined as the percentage of patients achieving best response of CR.
Time Frame
Up to 30 months
Title
Time to Response (TTR)
Description
TTR is defined as time from first dose of study drug to time of meeting criteria for CR or PR, whichever comes first.
Time Frame
Up to 30 months
Title
Duration of Response (DOR)
Description
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.
Time Frame
Up to 30 months
Title
Duration of Complete Response
Description
Duration of CR is defined as time from achieving CR to time of progression or starting another LGLL treatment, whichever comes first.
Time Frame
Up to 30 months
Title
Time to Complete Response
Description
Time to CR is defined as time from first dose of study drug to time of CR
Time Frame
Up to 30 months
Title
Duration of Complete Response with Normalization of PB LGL Count
Description
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).
Time Frame
Up to 30 months
Title
Progression Free Survival
Description
PFS is defined as time from first dose of study drug to time of disease progression or starting another LGLL treatment, whichever comes first
Time Frame
Up to 30 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: 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. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Richard Corona
Phone
813-745-3465
Email
Richard.Corona@moffitt.org
First Name & Middle Initial & Last Name or Official Title & Degree
Ning Dong, MD, MS
Phone
813-745-7673
Email
ning.dong@moffitt.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ning Dong, MD, MS
Organizational Affiliation
Moffitt Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Richard Corona
Phone
813-745-3465
Email
Richard.Corona@moffitt.org
First Name & Middle Initial & Last Name & Degree
Ning Dong, MD, MS

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://moffitt.org/clinicaltrialssearch?DiseaseSite=&q=21035
Description
Moffitt Cancer Center Clinical Trial Search

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Siltuximab in Large Granular Lymphocytic Leukemia (LGLL)

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