Modified Melanoma Vaccine for High Risk or Low Residual Disease Patients

Malignant Melanoma Clinical Trial

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01898039
• Other study ID #: 0419-12-HMO-CTIL
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 2013
• Est. completion date: April 2019

Study information

• Verified date: September 2018
• Source: Hadassah Medical Organization
• Contact: Hani Steinberg, RN
• Phone: 972507874292
• Email: hanis[@]hadassah.org.il
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: April 2019
• Est. primary completion date: April 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Malignant Melanoma
• Melanoma

Intervention

Biological:
• A2/4-1BBL melanoma vaccine
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.

Procedure:
• DNP sensititzation
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.

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

Locations

Country	Name	City	State
Israel	Sharett Institute of Oncology, Hadassah Medical Organization	Jerusalem

Sponsors (1)

Lead Sponsor	Collaborator
Hadassah Medical Organization

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	grade 2-4 adverse events according to CTCEA criteria		Day 1
Primary	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
Primary	grade 2-4 adverse events according to CTCEA criteria		Day 28
Primary	grade 2-4 adverse events according to CTCEA criteria		Day 56
Primary	grade 2-4 adverse events according to CTCEA criteria		month 3
Primary	grade 2-4 adverse events according to CTCEA criteria		month 4
Primary	grade 2-4 adverse events according to CTCEA criteria		month 5
Primary	grade 2-4 adverse events according to CTCEA criteria		month 6
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	overall survival and disease free survival		D1, Mo6, Mo10, Mo14, Mo18, Mo20, Mo24 and every 4 months till year 5