Modified Melanoma Vaccine for High Risk or Low Residual Disease Patients

Allogeneic Vaccine Modified to Express HLA A2/4-1BB Ligand for High Risk or Low Residual Disease Melanoma Patients

This study is based on the hypothesis that stimulation of the immune response against the tumor can help destroy residual tumor in melanoma patients with very high risk for disease recurrence and in patients with relatively low tumor burden who already got first line treatment for their disease.

Ongoing clinical trials in the Hadassah Hospital have shown that vaccination of patients with a cell line of tumor cells from the patient himself, or with a combination of three cell lines that partially match the patient's cell characteristics, could improve the immune response against the tumor, was associated with improved disease-free and overall survival.

In this study, the investigators will evaluate the efficacy of a modified tumor cell vaccine, in terms of immune response,improved disease-free and overall survival. The vaccine consists of a cell line that has a high expression level of melanoma molecules, and has been genetically modified to induce a strong immune response.

Study Overview

• Status: Withdrawn
• Conditions: Metastatic Disease; High Risk HLA-A2+ Melanoma
• Intervention / Treatment: Biological: Melanoma vaccine modified to express HLA A2/4-1BB ligand

• Study Type: Interventional
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients included in this protocol must carry one or more of the following tissue typing alleles: HLA-A2, -A24, -A33, -B35, -B49, -CW04/12(04/08). We estimate that 50% of melanoma patients will be eligible.
2. Cutaneous malignant melanoma AJCC stage IIb (over 4 mm) or IIc (ulcerated melanoma over 4mm).
3. Metastatic melanoma AJCC stage III (nodal involvement, N1-3a,b) post surgical removal of lymph nodes.
4. Metastatic melanoma AJCC stage IV, completely resected.
5. Non cutaneous malignant melanoma of respective stages including uveal and mucosal melanoma.
6. Melanoma can be of either mutant or wild-type B-RAF.
7. Karnofsky performance status over 80 (Normal activity with effort).
8. No active cardio-respiratory disease.
9. Hematocrit over 25% and WBC over 3000.
10. Informed consent of the patient.

Exclusion Criteria:

1. Administration of cytotoxic drugs or extensive radiotherapy less than 28 days prior to protocol administration.
2. Active brain metastases requiring cortico-steroids.
3. Concurrent malignancy (other than skin cancer, carcinoma in situ of cervix and early stage prostate cancer).
4. Active serious infection.
5. Allergy to penicillin.
6. Patient's wish to withdraw from the study at any stage.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Melanoma vaccine

Biological: Melanoma vaccine modified to express HLA A2/4-1BB ligand; This study is designed for patients who had malignant melanoma and, following tumor removal, are now free of disease, or have only very minor residual disease, and are at a very high risk of disease recurrence. These patients will be treated with the A2/4-1BBL melanoma vaccine, a compatible melanoma cell line that has been engineered to express a molecule termed 4-1BBL, which enhances the chances of the cell line to be recognized by the patient's immune system, and to induce its stimulation. The hypothesis that drives the study states that the immune response against the cell line will also be effective against the residual tumor that may still be present in the body.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of adverse effects	For 20 weeks from the start of treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall and disease free survival	For at least five years

Other Outcome Measures

Outcome Measure	Time Frame
Emergence of anti-tumor T cell reactivity	To be measured one month after the last vaccine was admininstered, on average 18-20 weeks after treatment start

Collaborators and Investigators

• Sponsor: Hadassah Medical Organization

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2017
• Primary Completion (Estimated): March 1, 2019
• Study Completion (Estimated): March 1, 2019

Study Registration Dates

• First Submitted: December 20, 2012
• First Submitted That Met QC Criteria: May 23, 2013
• First Posted (Estimated): May 24, 2013

Study Record Updates

• Last Update Posted (Estimated): October 2, 2025
• Last Update Submitted That Met QC Criteria: September 29, 2025
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: vaccine; melanoma; Resectable AJCC stage IV; AJCC stages IIb-c, III; Patients with low-burden; failed; respond; one treatment line
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplastic Processes; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Neoplasm Metastasis; Melanoma
• Other Study ID Numbers: 0419-12-HMO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No