Modified Melanoma Vaccine for High Risk or Low Residual Disease Patients

Phase 1

• Conditions: Malignant Melanoma
• Interventions: Biological: A2/4-1BBL melanoma vaccine; Procedure: DNP sensititzation; Drug: Cyclophosphamide

• Registration Number: NCT01898039
• Lead Sponsor: Hadassah Medical Organization

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-05
• Study First Submitted: 2013-05-09
• Study First Submitted QC: 2013-07-10
• Study First Posted: 2013-07-12
• Status Verified: 2018-09
• Last Update Submitted: 2018-09-17
• Last Update Posted: 2018-09-18
• Primary Completion: 2019-04
• Study Completion: 2019-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

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 (>4 mm) or IIc (ulcerated melanoma >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-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.
6. Non cutaneous malignant melanoma of respective stages including uveal and mucosal melanoma.
7. Melanoma can be of either mutant or wild-type B-RAF.
8. Karnofsky performance status > 80 (Normal activity with effort).
9. No active cardio-respiratory disease.
10. Not pregnant or nursing. Women must take contraceptives during the treatment period.Hematocrit >25% and WBC >3000.
11. 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 corticosteroids.
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 will to withdraw from the study at any stage.
7. HIV and chronic hepatitis B and C carrier

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
A2/4-1BBL melanoma vaccine	A2/4-1BBL melanoma vaccine	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.
A2/4-1BBL melanoma vaccine	DNP sensititzation	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.
A2/4-1BBL melanoma vaccine	Cyclophosphamide	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.

Primary Outcome Measures

Name	Time	Method
grade 2-4 adverse events according to CTCEA criteria	month 6
monitoring anti-tumor immune response	month 6	Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response

Secondary Outcome Measures

Name	Time	Method
overall survival and disease free survival	D1, Mo6, Mo10, Mo14, Mo18, Mo20, Mo24 and every 4 months till year 5

Trial Locations

Locations (1)

Sharett Institute of Oncology, Hadassah Medical Organization; 🇮🇱 Jerusalem, Israel