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Study Of Intratumoral G100 In Cutaneous T Cell Lymphoma

Primary Purpose

Lymphoma, T-Cell, Cutaneous

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Intratumoral G100
Sponsored by
Yale University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma, T-Cell, Cutaneous

Eligibility Criteria

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

Inclusion Criteria:

  1. Cutaneous T-cell lymphoma with persistent, relapsed or refractory disease following at least two prior therapies including at least one systemic therapy. Patients with aggressively progressing disease as per the investigator's assessment are not eligible.
  2. Skin lesions accessible for intratumoral injection and at least one additional site of disease outside the radiation field for assessment of distal (abscopal) response.
  3. ≥ 18 years of age.
  4. Life expectancy of ≥ 6 months per the investigator.
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  6. Electrocardiogram (ECG) without evidence of clinically significant ischemia or arrhythmia
  7. If female of childbearing potential (FCBP), willing to undergo pregnancy testing and agrees to use two methods of birth control or is considered highly unlikely to conceive during the dosing period and for three months after last study treatment.
  8. If male and sexually active with a FCBP, must agree to use effective contraception such as latex condom or is sterile (e.g. following a surgical procedure) during the dosing period and for three months after last study treatment.

Exclusion Criteria:

  1. Cancer therapies, including chemotherapy, radiation (non-study regimen related), within 4 weeks prior to the first scheduled G100 dose; histone deacetylase (HDAC) inhibitors and retinoids or interferon (IFN) or methotrexate or extracorporeal photopheresis (ECP) within 2 weeks
  2. Investigational therapy within 4 weeks prior to G100 dosing
  3. Inadequate organ function including:

    1. Marrow: Peripheral blood leukocyte count (WBC) < 3000/(cubic millimeter)mm3, absolute neutrophil count ≤ 1000/mm3, platelets < 100,000/mm3, or hemoglobin < 10 grams per deciliter (gm/dL).
    2. Hepatic: alanine aminotransferase (ALT), and aspartate aminotransferase (AST)> 2.5 x upper limit of normal (ULN), total serum bilirubin > 1.5 x ULN (patients withGilbert's Disease may be included if their total bilirubin is ≤3.0 (milligram) mg/dL)
    3. Renal: Serum creatinine ≤2 mg/dL
  4. Significant immunosuppression from:

    1. Concurrent, recent (≤ 4 weeks ago) or anticipated treatment with systemic corticosteroids greater than a maintenance dose for adrenal insufficiency (10 mg daily)
    2. Other immunosuppressive medications (e.g.,methotrexate, cyclosporine, azathioprine)
  5. Pregnant or nursing
  6. Myocardial infarction within 6 months of study initiation, active cardiac ischemia or New YorkHeart Association (NYHA) Grade III or IV heart failure
  7. History of other cancer within 2 years (except non-melanoma cutaneous malignancies, treated prostate cancer and cervical carcinoma in situ). Chronic lymphocytic leukemia (CLL) or low grade B-cell lymphoma will be considered on a case-by-case basis.
  8. Recent (< 1 week ago) clinically significant infection or active tuberculosis or evidence of active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection.
  9. Central nervous system involvement with lymphoma, including parenchymal and leptomeningeal disease.
  10. Significant autoimmune disease with the exception of alopecia, vitiligo, hypothyroidism or other conditions that have never been clinically active or were transient and have completely resolved and require no ongoing therapy.
  11. Psychiatric, other medical illness or other condition that in the opinion of the principal investigator prevents compliance with study procedures or ability to provide valid informed consent.
  12. History of significant adverse or allergic reaction to any component of G100 trial regimens.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    G100 injections

    Arm Description

    All patients will receive 6 intratumoral G100 injections alone over 5 weeks. There will be a 4-week break for restaging. Patients will receive another 6 doses of G100 with either topical nitrogen mustard for 2 days before each dose or local radiotherapy (2 Gy daily x 2 days) prior to G100 to the injected lesion to assess the response to combination therapy. After the first 4 doses, nitrogen mustard is optional and can be omitted at the discretion of the investigator.

    Outcomes

    Primary Outcome Measures

    Clinical response will be assessed with the modified Severity Weighted Assessment Tool
    Clinical response will be assessed with the modified Severity Weighted Assessment Tool [mSWAT].
    Clinical response will be assessed by the composite assessment of index lesion severity
    Clinical response will be assessed by the composite assessment of index lesion severity [CAILS])

    Secondary Outcome Measures

    Abscopal tumor response will be assessed with the modified Severity Weighted Assessment Tool
    Tumor response will be assessed with the modified Severity Weighted Assessment Tool [mSWAT].
    Abscopal tumor response will be assessed by the composite assessment of index lesion severity
    Tumor response will be assessed by the composite assessment of index lesion severity [CAILS]).

    Full Information

    First Posted
    November 13, 2018
    Last Updated
    December 16, 2019
    Sponsor
    Yale University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03742804
    Brief Title
    Study Of Intratumoral G100 In Cutaneous T Cell Lymphoma
    Official Title
    Pilot Phase 2 Study of Intratumoral G100 in Patients With Cutaneous T Cell Lymphoma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    December 2019
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Study sponsor sold and the new company would not support the study.
    Study Start Date
    June 2019 (Anticipated)
    Primary Completion Date
    December 2019 (Anticipated)
    Study Completion Date
    December 2022 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Yale University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The overall goal of this study is to evaluate the safety and immunogenicity of repeat-dose intratumoral G100 administration in patients with Cutaneous T Cell Lymphoma (CTCL) alone (Part 1) and following standard local radiation therapy or topical nitrogen mustard application (Part 2). Plaque, patch, or tumor lesions of CTCL may be injected. Disease will be assessed in all sites, including skin, nodes, and blood.
    Detailed Description
    This is a pilot, Phase II study of intratumoral or intralesional injection of G100 alone (Part 1) and in conjunction with topical nitrogen mustard (HN2) or radiotherapy (Part 2) in patients with CTCL to generate anti-tumor immune responses. To confirm the safety of the injections in this population, enrollment of the first four patients will be staggered by at least 21 days each. If there are no grade 3 adverse events following the first 4 injections in the first 3 patients, then subsequent patients can be enrolled without restriction to timing. Part 1: All patients will receive 6 intratumoral G100 injections alone over 5 weeks (first dose on Day 0, second on Day 5-7, and then weekly thereafter; up to Week 5) to assess the response to G100 alone. Response in target lesions will be measured by CAILS and abscopal effect will be measured by Modified Severity Weighted Assessment Tool (MSWAT). If applicable, peripheral blood flow cytometry will be used to assess response of circulating tumor cells. There will be a 4-week break for restaging. Part 2: Patients will receive another 6 doses of G100 with either topical nitrogen mustard for 2 days or local radiotherapy (2 Gy daily x 2 days) prior to G100 to the injected lesion to assess the response to combination therapy. After the first 4 doses, nitrogen mustard is optional and can be omitted at the discretion of the investigator. Response in target lesions will be measured by Composite assessment of index lesion severity (CAILS) and abscopal effect will be measured by MSWAT. If applicable, peripheral blood flow cytometry will be used to assess response of circulating tumor cells. Dose regimen interruption in a single patient may be made by the clinical investigator if it is deemed in the best interest of patient safety. Tumor imaging will be performed during the screening visit (baseline) in patients with blood involvement, palpable nodes, or tumor stage disease (scans done within 4 weeks of study entry are admissible), and in patients with clinically suspicious positive scans (nodes felt to be involved, standardized uptake value (SUV) 4 or greater on positron emission tomography (PET), imaging will be repeated at the completion of 6 weeks of dosing Circulating Sezary cells will be followed if present at baseline. Quantitation of Sezary cells will be done by flow cytometry using appropriate markers. Pre- and post-treatment tumor biopsies will be obtained for histologic review and exploratory immune analyses, including cell phenotype and genomic analyses of T cells. On-treatment biopsies will be performed at Week 3 of both Parts 1 and 2 of the study. Peripheral blood will be drawn for immune assays and other biomarker tests at time points listed in the Schedule of Events and Study Procedures. Primary Objective To evaluate the safety and to observe clinical responses (by MSWAT and CAILS) with intratumoral G100 alone and with G100 in combination with agents to induce apoptosis (local radiotherapy or topical nitrogen mustard) in patients with CTCL. Secondary Objectives To assess abscopal tumor responses in non-treated, distal tumor sites by MSWAT and CAILS tools. To evaluate pre-and post-regimen tumor tissue and blood for exploratory biomarkers of immunologic and tumor response.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Lymphoma, T-Cell, Cutaneous

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    G100 injections
    Arm Type
    Experimental
    Arm Description
    All patients will receive 6 intratumoral G100 injections alone over 5 weeks. There will be a 4-week break for restaging. Patients will receive another 6 doses of G100 with either topical nitrogen mustard for 2 days before each dose or local radiotherapy (2 Gy daily x 2 days) prior to G100 to the injected lesion to assess the response to combination therapy. After the first 4 doses, nitrogen mustard is optional and can be omitted at the discretion of the investigator.
    Intervention Type
    Biological
    Intervention Name(s)
    Intratumoral G100
    Intervention Description
    G100 agent is a potent Toll-like receptor (TLR)4 agonist. G100 is composed of glucopyranosyl lipid A (GLA) formulated in a stable emulsion (SE). GLA is a fully synthetic TLR4 agonist that is a potent stimulator of innate immune responses.
    Primary Outcome Measure Information:
    Title
    Clinical response will be assessed with the modified Severity Weighted Assessment Tool
    Description
    Clinical response will be assessed with the modified Severity Weighted Assessment Tool [mSWAT].
    Time Frame
    From baseline through follow-up, up to 12 months.
    Title
    Clinical response will be assessed by the composite assessment of index lesion severity
    Description
    Clinical response will be assessed by the composite assessment of index lesion severity [CAILS])
    Time Frame
    From baseline through follow-up, up to 12 months.
    Secondary Outcome Measure Information:
    Title
    Abscopal tumor response will be assessed with the modified Severity Weighted Assessment Tool
    Description
    Tumor response will be assessed with the modified Severity Weighted Assessment Tool [mSWAT].
    Time Frame
    From baseline through follow-up, up to 12 months.
    Title
    Abscopal tumor response will be assessed by the composite assessment of index lesion severity
    Description
    Tumor response will be assessed by the composite assessment of index lesion severity [CAILS]).
    Time Frame
    From baseline through follow-up, up to 12 months.

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Cutaneous T-cell lymphoma with persistent, relapsed or refractory disease following at least two prior therapies including at least one systemic therapy. Patients with aggressively progressing disease as per the investigator's assessment are not eligible. Skin lesions accessible for intratumoral injection and at least one additional site of disease outside the radiation field for assessment of distal (abscopal) response. ≥ 18 years of age. Life expectancy of ≥ 6 months per the investigator. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Electrocardiogram (ECG) without evidence of clinically significant ischemia or arrhythmia If female of childbearing potential (FCBP), willing to undergo pregnancy testing and agrees to use two methods of birth control or is considered highly unlikely to conceive during the dosing period and for three months after last study treatment. If male and sexually active with a FCBP, must agree to use effective contraception such as latex condom or is sterile (e.g. following a surgical procedure) during the dosing period and for three months after last study treatment. Exclusion Criteria: Cancer therapies, including chemotherapy, radiation (non-study regimen related), within 4 weeks prior to the first scheduled G100 dose; histone deacetylase (HDAC) inhibitors and retinoids or interferon (IFN) or methotrexate or extracorporeal photopheresis (ECP) within 2 weeks Investigational therapy within 4 weeks prior to G100 dosing Inadequate organ function including: Marrow: Peripheral blood leukocyte count (WBC) < 3000/(cubic millimeter)mm3, absolute neutrophil count ≤ 1000/mm3, platelets < 100,000/mm3, or hemoglobin < 10 grams per deciliter (gm/dL). Hepatic: alanine aminotransferase (ALT), and aspartate aminotransferase (AST)> 2.5 x upper limit of normal (ULN), total serum bilirubin > 1.5 x ULN (patients withGilbert's Disease may be included if their total bilirubin is ≤3.0 (milligram) mg/dL) Renal: Serum creatinine ≤2 mg/dL Significant immunosuppression from: Concurrent, recent (≤ 4 weeks ago) or anticipated treatment with systemic corticosteroids greater than a maintenance dose for adrenal insufficiency (10 mg daily) Other immunosuppressive medications (e.g.,methotrexate, cyclosporine, azathioprine) Pregnant or nursing Myocardial infarction within 6 months of study initiation, active cardiac ischemia or New YorkHeart Association (NYHA) Grade III or IV heart failure History of other cancer within 2 years (except non-melanoma cutaneous malignancies, treated prostate cancer and cervical carcinoma in situ). Chronic lymphocytic leukemia (CLL) or low grade B-cell lymphoma will be considered on a case-by-case basis. Recent (< 1 week ago) clinically significant infection or active tuberculosis or evidence of active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection. Central nervous system involvement with lymphoma, including parenchymal and leptomeningeal disease. Significant autoimmune disease with the exception of alopecia, vitiligo, hypothyroidism or other conditions that have never been clinically active or were transient and have completely resolved and require no ongoing therapy. Psychiatric, other medical illness or other condition that in the opinion of the principal investigator prevents compliance with study procedures or ability to provide valid informed consent. History of significant adverse or allergic reaction to any component of G100 trial regimens.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Francine Foss, MD
    Organizational Affiliation
    Yale University
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    Study Of Intratumoral G100 In Cutaneous T Cell Lymphoma

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