Stage IIIC Melanoma Clinical Trial
Official title:
A Phase I Study to Assess the Efficacy and Safety of Autologous Tumor Infiltrating Lymphocytes (LN144) With Adjuvant Pembrolizumab for Treatment of Immunotherapy Naïve Patients With High Risk Stage IIIb-dResectable Melanoma
The purpose of this study is to evaluate the efficacy of adjuvant adoptive cell therapy (ACT) via infusion of LN-144 (autologous TIL) followed by interleukin-2 (IL-2) after a nonmyeloablative lymphodepletion (NMA-LD) preparative regimen, followed by Pembrolizumab.
Status | Not yet recruiting |
Enrollment | 12 |
Est. completion date | July 2028 |
Est. primary completion date | January 2028 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Must have a confirmed diagnosis of resectable, Stage III, High-Risk melanoma defined by AJCC v8 as Stage IIIB, IIIC, or IIID. - Disease must be resected to no evidence of disease on imaging and no gross disease residually with the exception of positive microscopic margin. No prior treatment with immunotherapy. - One (1) lesion at least 1.5cm in size (solitary or aggregate) available for TIL harvesting that has not undergone prior embolization or RT in prior 3 months unless subsequent growth is demonstrated. - Palliative radiation therapy is permitted so long as it does not involve lesions being selected for TIL. Washout is not required if all related toxicities have resolved to = Grade 1 as per CTCAE v 5.0 - Previous surgical procedure(s) is/are permitted provided that wound healing has occurred, all complications have resolved, and at least 14 days have elapsed (for major operative procedures) prior to the tumor resection. - Patients must have a washout period = 21 days from prior anti-cancer therapy(ies) to the start of the planned NMA-LD pre-conditioning regimen. - Patients must be = 18 years of age at the time of consent. - Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and an estimated life expectancy of = 3 months in the opinion of the Investigator. - Patients must have the following hematologic parameters:• Absolute neutrophil count (ANC) = 1000/mm3, •Hemoglobin (Hb) = 9.0 g/dL, •Platelet = 100,000/mm3 - Patients must have adequate organ function: •Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 times the upper limit of normal (= 3 × ULN); patients with liver metastasis = 5 × ULN, •Estimated creatinine clearance (eCrCl) = 40 mL/min using the Cockcroft-Gault formula at Screening, •Total bilirubin = 2 mg/dL, •Patients with Gilbert's syndrome must have a total bilirubin = 3 mg/dL - Patients of childbearing potential (or female partners of male participants) must be willing to take the appropriate precaution to avoid pregnancy or fathering a child for the duration of the study and practice an approved, highly effective method of birth control during treatment and for 12 months after their last dose of IL-2. - Approved methods of birth control are as follows: Combined (estrogen and progesterone containing) hormonal birth control associated with inhibition of ovulation: oral, intravaginal, transdermal, Progesterone-only hormonal birth control associated with inhibition of ovulation: oral, injectable, implantable, Intrauterine device (IUD), Intrauterine hormone-releasing system (IUS), Bilateral tubal occlusion, Vasectomized partner, True sexual abstinence when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar ovulation, symptothermal, post-ovulation methods) is not acceptable - Patients (or legally authorized representative) must have the ability to understand the requirements of the study, have provided written informed consent as evidenced by signature on an ICF approved by an Institutional Review Board/Independent Ethics Committee (IRB/IEC), and agree to abide by the study restrictions and return to the site for the required assessments, including the OS Follow-up Period. Exclusion Criteria: - Patients who have received an organ allograft or prior cell transfer therapy within the past 20 years that included a non-myeloablative or myeloablative chemotherapy regimen. - Patients with melanoma of uveal/ocular origin. - Patients who have a history of hypersensitivity to any component or excipient of LN-144 or other study drugs: - NMA-LD preparative regimen (cyclophosphamide, mesna, and fludarabine), - Proleukin®, aldesleukin, IL-2, - Pembrolizumab, - Antibiotics (ABX) of the aminoglycoside group (i.e., streptomycin, gentamicin); except those who are skin-test negative for gentamicin hypersensitivity, - Any component of the LN-144 infusion product formulation including dimethyl sulfoxide (DMSO), human serum albumin (HSA), IL-2, and dextran-40. - Patients with symptomatic and/or untreated brain metastases (of any size and any number). - Patients who are on chronic systemic steroid therapy except for those requiring steroid therapy for management of adrenal insufficiency; these patients may receive no more than 10 mg of prednisone or its equivalent daily. - Patients who are pregnant or breastfeeding. - Patients who have active medical illness(es) that would pose increased risk for study participation, including: active systemic infections requiring systemic ABX, coagulation disorders, or other active major medical illnesses of the cardiovascular, respiratory, or immune systems. - Patients must have a negative syphilis assay (per local standard, e.g., rapid plasma reagin [RPR], venereal disease research laboratory [VDRL]) and be seronegative for the human immunodeficiency virus (HIV1 and HIV2 antibody titers). Patients with positive serology for hepatitis B virus surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) or hepatitis C virus (anti-HCV) indicating acute or chronic infection must have the corresponding polymerase chain reaction (PCR) assay; patients may be enrolled if the viral load by PCR is undetectable with/without active treatment. Additional serology testing may be required depending on local prevalence of certain viral exposures - Patients who have any form of primary immunodeficiency (e.g., severe combined immunodeficiency disease [SCID] and acquired immunodeficiency syndrome [AIDS]) - Patients who have received a live or attenuated vaccination within 28 days prior to the start of NMA-LD pre-conditioning regimen. - Participant has an LVEF < 45% and is New York Heart Association (NYHA) Class 1. For participants = 60 years of age OR who have a history of clinically relevant cardiac disease, no irreversible wall movement abnormality is demonstrated on a cardiac stress test (or equivalent local standard stress test). Participants with an abnormal cardiac stress test may be considered for study participation if they have adequate ejection fraction and cardiology clearance with approval of the Investigator. - Patients who have obstructive or restrictive pulmonary disease and have a documented forced expiratory volume in 1 second (FEV1) of = 60% of predicted normal: - If a patient is not able to perform reliable spirometry due to abnormal upper airway anatomy (i.e., tracheostomy), a 6-minute walk test may be used to assess pulmonary function., - Patients who are unable to walk a distance of at least 80% predicted for age and sex or demonstrates evidence of hypoxia at any point during the test (SpO2 < 90%) are excluded. - Patients who have had another primary malignancy within the previous three (3) years (with the exception of carcinoma in situ of the breast, cervix, or bladder; localized prostate cancer; non-melanoma skin cancer that has been adequately treated; or other cancers that in the opinion of the investigator do not place the subject at a significantly higher risk). - Active infections, including COVID-19, within 30 days - Participated in another clinical study with an investigational product within 21 days of the initiation of treatment. |
Country | Name | City | State |
---|---|---|---|
United States | Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center | Cleveland | Ohio |
Lead Sponsor | Collaborator |
---|---|
James Isaacs, MD |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | LN-144 Efficacy | measured as the rate of RFS (Relapse-Free Survival) | 1 year following TIL infusion | |
Primary | LN-144 Safety Profile | measured by the incidence Serous Adverse Events (SAE) | Within 30 days of LN-144 administration | |
Secondary | LN-144+ Pembrolizumab Efficacy Overall Survival (OS) | measured using overall survival (OS). This is the length of time from the start of treatment to a given time point that measures participants on the study that are still alive | 1 year after initial treatment | |
Secondary | LN-144+ Pembrolizumab Efficacy Relapse-Free Survival (RFS) | measured using Relapse-free survival described as the length of time after primary treatment for a cancer ends that the patient survives without any signs or symptoms of that cancer | 1 year after initial treatment | |
Secondary | LN-144+ Pembrolizumab Efficacy Distant Metastasis-Free Survival (DMFS) | measured using distant metastasis-free survival (DMFS). This is the length of time from the start of treatment for cancer that a patient is still alive and the cancer has not spread to other parts of the body. | 1 year after inital treatment | |
Secondary | LN-144 Safety Profile | Incidence of adverse events following LN144 administration | within 12 months of LN144 administration | |
Secondary | Location of relapse | In participants who relapse, the location of the relapse will be located using standard imaging and physical exam | Up to 3 years | |
Secondary | Rate of Achievable Recruitment | The number of participants enrolled will be counted in which an "achievable" recruitment is considered to be 1 participant every 2-3 months. | 2 years from the study start date |
Status | Clinical Trial | Phase | |
---|---|---|---|
Withdrawn |
NCT01216787 -
RO4929097 in Treating Patients With Stage IIIB, Stage IIIC, or Stage IV Melanoma That Can Be Removed by Surgery
|
Phase 2 | |
Active, not recruiting |
NCT01026324 -
Dinaciclib in Treating Patients With Stage III-IV Melanoma
|
Phase 1/Phase 2 | |
Completed |
NCT01748747 -
Vaccine Therapy and Resiquimod in Treating Patients With Stage II-IV Melanoma That Has Been Removed By Surgery
|
Early Phase 1 | |
Terminated |
NCT01316692 -
Aurora A Kinase Inhibitor MLN8237 in Treating Patients With Unresectable Stage III-IV Melanoma
|
Phase 2 | |
Terminated |
NCT02203604 -
High-Dose Aldesleukin and Ipilimumab in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed By Surgery
|
Phase 2 | |
Completed |
NCT02094872 -
Molecularly Targeted Therapy in Treating Patients With BRAF Wild-type Melanoma That is Metastatic
|
Phase 2 | |
Terminated |
NCT01835184 -
Cabozantinib-S-Malate and Vemurafenib in Treating Patients With Solid Tumors or Melanoma That is Metastatic or That Cannot Be Removed By Surgery
|
Phase 1 | |
Terminated |
NCT02236546 -
FDG-PET in Advanced Melanoma
|
N/A | |
Completed |
NCT00085189 -
Vaccine Therapy in Treating Patients With Stage IIC-IV Melanoma
|
Phase 2 | |
Completed |
NCT01127451 -
Study of Denileukin Diftitox in Participants With Stage IIIC and Stage IV Melanoma
|
Phase 2 | |
Active, not recruiting |
NCT01898403 -
Lymph Node Mapping Using Indocyanine Green Solution in Diagnosing Patients With Malignant Melanoma
|
N/A | |
Completed |
NCT00089063 -
Vaccine Therapy With or Without Sargramostim in Treating Patients Who Have Undergone Surgery for Melanoma
|
Phase 2 | |
Completed |
NCT02296112 -
Trametinib in Treating Patients With Advanced Melanoma With BRAF Non-V600 Mutations
|
Phase 2 | |
Terminated |
NCT01701037 -
Dabrafenib Alone and in Combination With Trametinib Before Surgery in Treating Patients With Locally or Regionally Advanced Melanoma That Can Be Removed By Surgery
|
Phase 2 | |
Terminated |
NCT01519427 -
Selumetinib and Akt Inhibitor MK2206 in Treating Patients With Stage III or Stage IV Melanoma Who Failed Prior Therapy With Vemurafenib or Dabrafenib
|
Phase 2 | |
Terminated |
NCT01533948 -
Axitinib in Treating Patients With Melanoma That is Metastatic or Cannot Be Removed by Surgery
|
Phase 2 | |
Completed |
NCT02166255 -
APN401 in Treating Patients With Melanoma, Kidney Cancer, Pancreatic Cancer, or Other Solid Tumors That Are Metastatic or Cannot Be Removed By Surgery
|
Phase 1 | |
Completed |
NCT01321437 -
Study of the Anti-Angiogenesis Agent Axitinib in Patients With Stage III Malignant Melanoma
|
Phase 2 | |
Completed |
NCT00436605 -
Dasatinib in Treating Patients With Stage III Melanoma That Cannot Be Removed By Surgery or Stage IV Melanoma
|
Phase 2 | |
Withdrawn |
NCT02507076 -
Isolated Limb Perfusion With Melphalan in Treating Patients With Stage IIIB-IV Melanoma or Sarcoma
|
N/A |