Adoptive T Cell Immunotherapy for Advanced Melanoma Using Engineered Lymphocytes

NCT02870244 | Recruiting Phase 1 DMC

• 1 other identifier: 203729
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Phase I clinical trial to determine the Phase II dose of autologous TIL 1383I TCR gene modified T Cells using a retrovirus. This is a novel National Cancer Institute (NCI) funded investigator initiated therapy for patients with advanced melanoma.

Conditions

Melanoma

Keywords

Melanoma; Gene Therapy; Adoptive T-Cell Transfer; IL-2

Outcome Measures

Primary Outcomes (1)

• Approximately 18 patients with Grade 2 through Grade 5 Adverse Events that are related to study drug, graded according to NCI CTCAE Version 4.0

  Establish a recommended phase II dose of autologous T cell receptor transduced T cells by evaluating unexpected Grade 2 adverse events through Grade 5 regardless of attribution, all toxicities attributed to the cells, and all incidences of intubation including the duration and reason for intubation.

  4 weeks

Secondary Outcomes (4)

• Immunologic changes in T cell count

  Baseline and 4 weeks

• Audiologic changes of Grade 2 or higher as related to study drug, graded according to NCI CTCAE Version 4.0

  Baseline and 4 weeks

• Ophthalmologic changes or development of Uveitis of Grade 2 or higher as related to study drug, graded according to NCI CTCAE Version 4.0

  Baseline and 4 weeks

• CT scans or physical examination from approximately 18 patients will be used to evaluate for a clinical objective response using RECIST Guideline Version 1.1

  Baseline and 4 weeks

Study Arms (1)

Escalating Doses

EXPERIMENTAL

Three patients will be treated at the first \& each subsequent dose level. Patients will be observed for 30 days post T cell infusion. If there was one DLT in the first 3 patients, an additional 3 patients will be treated at that level. If no additional DLTs are observed (for a total of 1 DLT in 6 patients) then the dose will be escalated. If two patients in the first 3 patients at a dose level experience a DLT, the dose will be de-escalated to the previous level \& an additional 3 patients will be enrolled at that level if 6 have not yet been treated at that level. The maximum tolerated dose (MTD) is defined as the highest dose at which 0 or 1 patient in six has experienced a DLT. If 2 or 3 patients in the first 3 patients experience a DLT at the first dose level, the study will terminate.

Biological: Escalating Doses

Interventions

Escalating Doses BIOLOGICAL

Subjects will receive a single infusion of autologous bulk TIL 13831 TCR transduced T cells supported with low dose IL-2. Autologous bulk TIL 13831 TCR transduced T cells means the infusion will consist of a polyclonal mixture of CD4 + and CD8+ T Cells expressing the TIL 13831 TCR. Subjects in Cohort 1 will receive 7.5 x 10\^6/kg TIL 1383I TCR transduced T cells. Subjects in Cohort 2 will receive 2.5 x 10\^7/kg TIL 1383I TCR transduced T cells. Subjects in Cohort 3 will receive 7.5 x 10\^7/kg TIL 1383I TCR transduced T cells.

Escalating Doses

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a diagnosis of metastatic melanoma which is evaluable either clinically or radiologically.
• Patients must be 18 years of age or older.
• Patients must consent to be in the study and must have signed and dated an approved consent form, which conforms to federal and institutional guidelines.
• Patients must have a performance status (PS) of 0 or 1 ECOG PS scale.
• Patients must have the ability to provide written informed consent prior to study specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time.
• Patients melanoma must be positive for both tyrosinase and HLA-A2 pathologic review from FNA, core or excisional biopsy of lesion.
• Cardiac ejection fraction greater than 50 percent as determined by screening echocardiogram.
• Patients that have undergone treatment with anti-CTLA-4, Cytotoxic T-Lymphocyte Antigen 4, antibody must have at least 6 weeks from last dose of CTLA-4 antibody and evidence of tumor progression before they can be enrolled into this study.
• Patients that have undergone treatment with anti-PD-1, Programmed Death Receptor 1, Blockade or anti-PD-L1 antibody must have at least 4 weeks from last dose of antibody and evidence of tumor progression before they can be treated in this study.
• Patients with V600E mutations are eligible if they have failed an approved BRAF inhibitor or MEK inhibitor therapy or have refused treatment with an approved BRAF inhibitor or MEK inhibitor.
• Patients treated with prior Interleukin-2 (IL-2) are eligible.
• Sufficient cardiopulmonary reserve for IL-2 per institutional guidelines.

You may not qualify if:

• Special classes of subjects such as fetuses, pregnant women, children, prisoners, institutionalized individuals, or others who are likely to be vulnerable.
• ECOG performance status of 2 or greater.
• Patients with a history metastatic melanoma involving the brain will be excluded if they have active disease or have had active disease within the prior three months that was not controlled with surgery or radiotherapy.
• Patients taking steroids for disease control or pain management
• Patients must not be pregnant or nursing because of the potentially harmful effects of these agents on a developing fetus. Women or men of reproductive potential must have agreed to use an effective contraceptive method.
• Patients whose BRAF V600 mutation status is unknown should undergo an attempt to determine this information, patients who have a BRAF V600 mutation and are responding to BRAF with or without MEK inhibitor therapy, or have a BRAF V600 mutation and have not been offered the option of receiving BRAF with or without MEK inhibitor therapy for the treatment of their melanoma are excluded.
• No prior malignancy is allowed except for the following- adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for two years.
• Patients that have undergone immunotherapy targeting tyrosinase.
• Patients that have undergone immunotherapy in combination with non-myeloablative chemotherapy.
• Any of the following abnormal laboratory values Absolute neutrophil count less than 1.5 x 10\^9/L Platelet count less than 100 x 10\^9/L Serum bilirubin greater than 1.5 x upper limit of normal ULN Serum ALT, AST greater than 2.5 x ULN Serum ALP greater than 2 x ULN Serum Albumin less than 2.5 g dL International Normalized Ratio, INR greater than 1.5 Serum creatinine calculated creatinine clearance by the method of Cockcroft and Gault, less than 50mL min.
• Patients should not have any evidence of active or uncontrolled infection requiring treatment with antibiotics.
• Any severe or poorly controlled systemic disease, for example hypertension, clinically significant cardiovascular, pulmonary, or metabolic disease, disorders of wound-healing, ulcer or bone fracture.
• Patients who have received any chemotherapy or investigational treatment within 4 weeks of study start.
• Known infection with HIV, HBV, or HCV.
• Known hypersensitivity to any of the components of the study drugs.

Sponsors & Collaborators

• Loyola University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Loyola University Medical Center

Maywood, Illinois, 60153, United States

RECRUITING

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Michael Nishimura, PhD

  Loyola University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael Nishimura, PhD

CONTACT

708-327-3241; mnishimura@lumc.edu

Ann Lau Clark, RN, MSN

CONTACT

708-327-3221; alausch@luc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 22, 2016
• First Posted: August 17, 2016
• Study Start: February 1, 2015
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: March 12, 2018

Record last verified: 2018-03

Locations

US (1)