Modified Vaccine for High Risk or Low Residual Melanoma Patients

NCT01898039 | Recruiting Phase 1

• 1 other identifier: 0419-12-HMO-CTIL
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Malignant Melanoma

Keywords

malignant melanoma; vaccine; cell line; high risk; residual disease

Outcome Measures

Primary Outcomes (14)

• grade 2-4 adverse events according to CTCEA criteria

  Day 1

• monitoring anti-tumor immune response

  Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response.

  Day 0

• grade 2-4 adverse events according to CTCEA criteria

  Day 28

• grade 2-4 adverse events according to CTCEA criteria

  Day 56

• grade 2-4 adverse events according to CTCEA criteria

  month 3

• grade 2-4 adverse events according to CTCEA criteria

  month 4

• grade 2-4 adverse events according to CTCEA criteria

  month 5

• grade 2-4 adverse events according to CTCEA criteria

  month 6

• monitoring anti-tumor immune response

  Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response

  Day 28

• monitoring anti-tumor immune response

  Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response

  Day 56

• monitoring anti-tumor immune response

  Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response

  month 3

• monitoring anti-tumor immune response

  Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response

  month 4

• monitoring anti-tumor immune response

  Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response

  month 5

• monitoring anti-tumor immune response

  Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response

  month 6

Secondary Outcomes (1)

• overall survival and disease free survival

  D1, Mo6, Mo10, Mo14, Mo18, Mo20, Mo24 and every 4 months till year 5

Study Arms (1)

A2/4-1BBL melanoma vaccine

EXPERIMENTAL

On days 1 and 2 patients will be sensitized to DNP by topically applying 0.1 ml of 2% DNP dissolved in acetone-corn oil (Sigma) to the inner aspect of the arm. On day 10, intravenous low dose cyclophosphamide, 300 mg/m2, will be administered at the day care unit. On day 14 the appropriate dose of irradiated M20/A2B cells will be injected into three adjacent sites on the upper arm or thigh, avoiding limbs where lymph node dissection had been previously performed. Four additional doses of the vaccine will be administered at intervals of 21 days.

Biological: A2/4-1BBL melanoma vaccine; Procedure: DNP sensititzation; Drug: Cyclophosphamide

Interventions

A2/4-1BBL melanoma vaccine BIOLOGICAL

On days 14, 35, 56, 77 and 98 the appropriate dose of irradiated M20/A2B cells will be injected into three adjacent sites on the upper arm or thigh, avoiding limbs where lymph node dissection had been previously performed.

Also known as: M20/A2B vaccine

A2/4-1BBL melanoma vaccine

DNP sensititzation PROCEDURE

Include brand names, serial numbers and code names, if applicable. Other names are used to improve search results on the ClinicalTrials.gov web site. On days 1 and 2 patients will be sensitized to DNP by topically applying 0.1 ml of 2% DNP dissolved in acetone-corn oil (Sigma) to the inner aspect of the arm.

A2/4-1BBL melanoma vaccine

Cyclophosphamide DRUG

On day 10, intravenous low dose cyclophosphamide, 300 mg/m2, will be administered.

A2/4-1BBL melanoma vaccine

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Cutaneous malignant melanoma AJCC stage IIb (\>4 mm) or IIc (ulcerated melanoma \>4mm).
• Metastatic melanoma AJCC stage III (nodal involvement, N1-3a,b) post-surgical removal of lymph nodes.
• Metastatic melanoma AJCC stage IV, completely resected.
• Non-resectable metastatic melanoma of low burden disease and normal LDH who have undergone at least two treatment lines, including chemotherapy (DTIC, temodal, taxanes, platinum compounds), anti-CTLA-4 (ipilimumab) and B-RAF inhibitor if harboring the V600E BRAF mutation in their tumor.
• Non cutaneous malignant melanoma of respective stages including uveal and mucosal melanoma.
• Melanoma can be of either mutant or wild-type B-RAF.
• Karnofsky performance status \> 80 (Normal activity with effort).
• No active cardio-respiratory disease.
• Not pregnant or nursing. Women must take contraceptives during the treatment period.Hematocrit \>25% and WBC \>3000.
• Informed consent of the patient.

You may not qualify if:

• Administration of cytotoxic drugs or extensive radiotherapy less than 28 days prior to protocol administration.
• Active brain metastases requiring corticosteroids.
• Concurrent malignancy (other than skin cancer, carcinoma in situ of cervix and early stage prostate cancer).
• Active serious infection.
• Allergy to penicillin.
• Patient's will to withdraw from the study at any stage.
• HIV and chronic hepatitis B and C carrier

Sponsors & Collaborators

• Hadassah Medical Organization: lead

Study Sites (1)

Sharett Institute of Oncology, Hadassah Medical Organization

Jerusalem, 91120, Israel

RECRUITING

MeSH Terms

Conditions

Melanoma; Neoplasm, Residual

Interventions

Cyclophosphamide

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Central Study Contacts

Hani Steinberg, RN

CONTACT

972507874292; hanis@hadassah.org.il

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2013
• First Posted: July 12, 2013
• Study Start: May 1, 2013
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: October 2, 2025

Record last verified: 2025-03

Locations

IL (1)