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Modified Melanoma Vaccine for High Risk or Low Residual Disease Patients

Primary Purpose

Malignant Melanoma

Status
Unknown status
Phase
Phase 1
Locations
Israel
Study Type
Interventional
Intervention
A2/4-1BBL melanoma vaccine
DNP sensititzation
Cyclophosphamide
Sponsored by
Hadassah Medical Organization
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malignant Melanoma focused on measuring malignant melanoma, vaccine, cell line, high risk, residual disease

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Sharett Institute of Oncology, Hadassah Medical OrganizationRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

A2/4-1BBL melanoma vaccine

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

overall survival and disease free survival

Full Information

First Posted
May 9, 2013
Last Updated
September 17, 2018
Sponsor
Hadassah Medical Organization
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1. Study Identification

Unique Protocol Identification Number
NCT01898039
Brief Title
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

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Unknown status
Study Start Date
May 2013 (undefined)
Primary Completion Date
April 2019 (Anticipated)
Study Completion Date
April 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hadassah Medical Organization

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Melanoma
Keywords
malignant melanoma, vaccine, cell line, high risk, residual disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
A2/4-1BBL melanoma vaccine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
A2/4-1BBL melanoma vaccine
Other Intervention Name(s)
M20/A2B vaccine
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
DNP sensititzation
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
On day 10, intravenous low dose cyclophosphamide, 300 mg/m2, will be administered.
Primary Outcome Measure Information:
Title
grade 2-4 adverse events according to CTCEA criteria
Time Frame
Day 1
Title
monitoring anti-tumor immune response
Description
Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response.
Time Frame
Day 0
Title
grade 2-4 adverse events according to CTCEA criteria
Time Frame
Day 28
Title
grade 2-4 adverse events according to CTCEA criteria
Time Frame
Day 56
Title
grade 2-4 adverse events according to CTCEA criteria
Time Frame
month 3
Title
grade 2-4 adverse events according to CTCEA criteria
Time Frame
month 4
Title
grade 2-4 adverse events according to CTCEA criteria
Time Frame
month 5
Title
grade 2-4 adverse events according to CTCEA criteria
Time Frame
month 6
Title
monitoring anti-tumor immune response
Description
Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response
Time Frame
Day 28
Title
monitoring anti-tumor immune response
Description
Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response
Time Frame
Day 56
Title
monitoring anti-tumor immune response
Description
Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response
Time Frame
month 3
Title
monitoring anti-tumor immune response
Description
Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response
Time Frame
month 4
Title
monitoring anti-tumor immune response
Description
Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response
Time Frame
month 5
Title
monitoring anti-tumor immune response
Description
Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response
Time Frame
month 6
Secondary Outcome Measure Information:
Title
overall survival and disease free survival
Time Frame
D1, Mo6, Mo10, Mo14, Mo18, Mo20, Mo24 and every 4 months till year 5

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hani Steinberg, RN
Phone
972507874292
Email
hanis@hadassah.org.il
Facility Information:
Facility Name
Sharett Institute of Oncology, Hadassah Medical Organization
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hani Steinberg, RN
Email
hanis@hadassah.org.il

12. IPD Sharing Statement

Learn more about this trial

Modified Melanoma Vaccine for High Risk or Low Residual Disease Patients

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