Study Of Intratumoral G100 In Cutaneous T Cell Lymphoma

NCT03742804 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 2000021483
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Lymphoma, T-Cell, Cutaneous

Outcome Measures

Primary Outcomes (2)

• Clinical response will be assessed with the modified Severity Weighted Assessment Tool

  Clinical response will be assessed with the modified Severity Weighted Assessment Tool \[mSWAT\].

  From baseline through follow-up, up to 12 months.

• 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 \[CAILS\])

  From baseline through follow-up, up to 12 months.

Secondary Outcomes (2)

• Abscopal tumor response will be assessed with the modified Severity Weighted Assessment Tool

  From baseline through follow-up, up to 12 months.

• Abscopal tumor response will be assessed by the composite assessment of index lesion severity

  From baseline through follow-up, up to 12 months.

Study Arms (1)

G100 injections

EXPERIMENTAL

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.

Biological: Intratumoral G100

Interventions

Intratumoral G100 BIOLOGICAL

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.

G100 injections

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yale University: lead

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Francine Foss, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2018
• First Posted: November 15, 2018
• Study Start: June 1, 2019
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2022
• Last Updated: December 18, 2019

Record last verified: 2019-12