Clinical trial NCT01898039: Modified Melanoma Vaccine for High Risk or Low Residual Disease Patients
Official title: Allogeneic Vaccine Modified to Express HLA A2/4-1BB Ligand for High Risk or Low Residual Disease Melanoma Patients - Phase I/II Study.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Malignant Melanoma
Keywords: malignant melanoma
vaccine
cell line
high risk
residual disease
Lead sponsor: Hadassah Medical Organization
Sponsor class: OTHER
First posted: 2013-07-12
Enrollment: 50
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: grade 2-4 adverse events according to CTCEA criteria
timeFrame: Day 1
measure: monitoring anti-tumor immune response
timeFrame: Day 0
measure: grade 2-4 adverse events according to CTCEA criteria
timeFrame: Day 28
measure: grade 2-4 adverse events according to CTCEA criteria
timeFrame: Day 56
measure: grade 2-4 adverse events according to CTCEA criteria
timeFrame: month 3
measure: grade 2-4 adverse events according to CTCEA criteria
timeFrame: month 4
measure: grade 2-4 adverse events according to CTCEA criteria
timeFrame: month 5
measure: grade 2-4 adverse events according to CTCEA criteria
timeFrame: month 6
measure: monitoring anti-tumor immune response
timeFrame: Day 28
measure: monitoring anti-tumor immune response
timeFrame: Day 56
measure: monitoring anti-tumor immune response
timeFrame: month 3
measure: monitoring anti-tumor immune response
timeFrame: month 4
measure: monitoring anti-tumor immune response
timeFrame: month 5
measure: monitoring anti-tumor immune response
timeFrame: month 6
Secondary outcomes:
measure: overall survival and disease free survival
timeFrame: D1, Mo6, Mo10, Mo14, Mo18, Mo20, Mo24 and every 4 months till year 5
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Sharett Institute of Oncology, Hadassah Medical Organization
Study officials:
References: