Modified melanoma cell-line vaccine for people at high risk of recurrence or with a small amount of remaining disease

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

This will test a modified melanoma cell-line vaccine that boosts immune recognition to see if it helps people who are disease-free after surgery or who have only a small amount of remaining melanoma but are at high risk of recurrence.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sex: All
• Sponsor: Hadassah Medical Organization (Academic / other)
• Drugs / interventions: ipilimumab, chemotherapy
• Locations: 1 site (Jerusalem)
• Trial ID: NCT01898039 on ClinicalTrials.gov

What this trial studies

This Phase 1/2 trial gives an A2/4-1BBL melanoma vaccine — a compatible melanoma cell line engineered to express the costimulatory molecule 4-1BBL — to patients who are disease-free after surgery or have minimal residual disease but face high recurrence risk. Cells are DNP-sensitized before administration and patients may receive low-dose cyclophosphamide to modulate the immune response, with enrollment restricted to patients carrying specific HLA alleles to ensure antigen compatibility. The approach aims to stimulate tumor-directed T cell responses against residual tumor cells by increasing recognition of tumor antigens presented by the vaccine cell line. The trial is run at Hadassah Medical Organization in Jerusalem and includes dose-escalation and early efficacy/safety cohorts.

Who should consider this trial

Good fit: Ideal candidates are adults with high-risk melanoma (stage IIb/IIc, stage III, or completely resected stage IV) or low-burden unresectable disease who have a Karnofsky performance status >80 and carry one of the required HLA alleles.

Not a fit: Patients who do not carry the required HLA alleles, who have high-burden progressive disease, poor performance status, or do not meet prior-treatment criteria are unlikely to receive benefit from this vaccine.

Why it matters

Potential benefit: If successful, the vaccine could lower the risk of melanoma coming back by helping the immune system clear remaining tumor cells.

How similar studies have performed: Cancer vaccines have elicited immune responses in prior trials but have shown limited clear survival benefits to date, though 4-1BBL-based strategies have demonstrated promising immune activation in early-phase studies.

Eligibility criteria

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

Where this trial is running

Jerusalem

• Sharett Institute of Oncology, Hadassah Medical Organization — Jerusalem, Israel (Recruiting)

Study contacts

• Study coordinator: Hani Steinberg, RN

Conditions Malignant Melanoma; malignant melanoma; vaccine; cell line; high risk; residual disease