Malignant MelanomaPhase 1/2NCT01898039
Modified Vaccine for High Risk or Low Residual Melanoma Patients
A Phase 1/2 study testing A2/4-1BBL melanoma vaccine, DNP sensititzation and Cyclophosphamide in people with Malignant Melanoma, run by Hadassah Medical Organization at 1 site in Israel.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Malignant Melanoma
- What is being tested?
- A2/4-1BBL melanoma vaccine, DNP sensititzation and Cyclophosphamide
- Type of treatment
- Vaccines, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteIsrael
- Study dates
- May 2013to Apr 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Show all 11Show fewer
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Israel1 site, 1 recruiting
- Recruiting
Sharett Institute of Oncology, Hadassah Medical Organization
Jerusalem, 91120
Hani Steinberg, RN, hanis@hadassah.org.il
About this study
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.
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.
- Conditions
- Malignant Melanoma
- Being tested
- A2/4-1BBL melanoma vaccine, DNP sensititzation, Cyclophosphamide
- Keywords
- malignant melanoma, vaccine, cell line, high risk, residual disease
- Medical subject headings
- Melanoma, Neoplasm, Residual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
A2/4-1BBL melanoma vaccineBiological
Also called M20/A2B 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.
DNP sensititzationProcedure or surgery
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.
CyclophosphamideDrug
On day 10, intravenous low dose cyclophosphamide, 300 mg/m2, will be administered.
| Study group | Role | What they receive |
|---|---|---|
| A2/4-1BBL melanoma vaccine | Experimental | 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. Receives: Biological: A2/4-1BBL melanoma vaccine; Procedure: DNP sensititzation; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
grade 2-4 adverse events according to CTCEA criteria
Measured: Day 1
monitoring anti-tumor immune response
Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response.
Measured: Day 0
grade 2-4 adverse events according to CTCEA criteria
Measured: Day 28
grade 2-4 adverse events according to CTCEA criteria
Measured: Day 56
grade 2-4 adverse events according to CTCEA criteria
Measured: month 3
grade 2-4 adverse events according to CTCEA criteria
Measured: month 4
grade 2-4 adverse events according to CTCEA criteria
Measured: month 5
grade 2-4 adverse events according to CTCEA criteria
Measured: month 6
monitoring anti-tumor immune response
Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response
Measured: Day 28
monitoring anti-tumor immune response
Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response
Measured: Day 56
monitoring anti-tumor immune response
Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response
Measured: month 3
monitoring anti-tumor immune response
Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response
Measured: month 4
monitoring anti-tumor immune response
Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response
Measured: month 5
monitoring anti-tumor immune response
Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response
Measured: month 6
Secondary outcomes (1)
overall survival and disease free survival
Measured: D1, Mo6, Mo10, Mo14, Mo18, Mo20, Mo24 and every 4 months till year 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2013 (estimated)
- Study startMay 2013
- Primary completionApr 2027 (estimated)
- Study completionApr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant MelanomaStudies of the same condition, open and under way.
- More trials run by Hadassah Medical OrganizationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hadassah Medical Organization
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01898039
- Sponsor's protocol ID
- 0419-12-HMO-CTIL
- Status last verified
- Mar 2025
- First submitted
- 9 May 2013
- Last updated
- 2 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01898039
- Acronym / sponsor ID
- 0419-12-HMO-CTIL
- Conditions
- Malignant Melanoma
- Keywords
- malignant melanoma, vaccine, cell line, high risk, residual disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Hadassah Medical OrganizationUniversity, hospital or other
- Study start
- May 2013
- Primary completion
- Apr 2027 (estimated)
- Study completion
- Apr 2027 (estimated)
- First posted
- 12 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| A2/4-1BBL melanoma vaccine | Experimental | Biological: A2/4-1BBL melanoma vaccine, Procedure: DNP sensititzation, Drug: CyclophosphamideOn 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| A2/4-1BBL melanoma vaccineAlso: M20/A2B vaccineOn 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. | Biological | A2/4-1BBL melanoma vaccine |
| DNP sensititzationInclude 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. | Procedure or surgery | A2/4-1BBL melanoma vaccine |
| CyclophosphamideOn day 10, intravenous low dose cyclophosphamide, 300 mg/m2, will be administered. | Drug | A2/4-1BBL melanoma vaccine |
Primary outcome
grade 2-4 adverse events according to CTCEA criteria
Time frame: Day 1
monitoring anti-tumor immune response
Time frame: Day 0
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
Time frame: Day 28
grade 2-4 adverse events according to CTCEA criteria
Time frame: Day 56
grade 2-4 adverse events according to CTCEA criteria
Time frame: month 3
grade 2-4 adverse events according to CTCEA criteria
Time frame: month 4
grade 2-4 adverse events according to CTCEA criteria
Time frame: month 5
grade 2-4 adverse events according to CTCEA criteria
Time frame: month 6
monitoring anti-tumor immune response
Time frame: Day 28
Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response
monitoring anti-tumor immune response
Time frame: Day 56
Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response
monitoring anti-tumor immune response
Time frame: month 3
Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response
monitoring anti-tumor immune response
Time frame: month 4
Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response
monitoring anti-tumor immune response
Time frame: month 5
Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response
monitoring anti-tumor immune response
Time frame: month 6
Anti-tumor immune response will be measured by delayed type hypersensitivity in vivo and by in vitro lymphocyte response
1 secondary outcome
overall survival and disease free survival
Time frame: D1, Mo6, Mo10, Mo14, Mo18, Mo20, Mo24 and every 4 months till year 5
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2025.
Related trials for Malignant Melanoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy
Melanoma
Active, not recruitingPhase 1/2
A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma
Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing A2/4-1BBL melanoma vaccine, DNP sensititzation and Cyclophosphamide in people with Malignant Melanoma, run by Hadassah Medical Organization at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hani Steinberg, RN (972507874292, hanis@hadassah.org.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
grade 2-4 adverse events according to CTCEA criteria (time frame: Day 1). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2025.