Malignant Melanoma of Skin Stage IIIPhase 2ABSIDENCT01973322
Vaccination With Autologous Dendritic Cells Loaded With Autologous Tumor Lysate or Homogenate Combined With Immunomodulating Radiotherapy and/or Preleukapheresis IFN-alfa in Patients With Metastatic Melanoma: a Randomized "Proof-of-principle" Phase II Study
A Phase 2 study testing arm 1: DC Vaccine + RT, arm 2: DC Vaccine + IFN-alfa and arm 3: both arm 1 and 2 + RT in people with Malignant Melanoma of Skin Stage III and Malignant Melanoma of Skin Stage IV, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 1 site in Italy.
Trial summary
Title: Vaccination with autologous dendritic cells loaded with autologous tumor lysate or homogenate combined with immunomodulating radiotherapy and/or preleukapheresis IFN-alfa in patients with metastatic melanoma: a randomized "proof-of-principle" phase II study. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Malignant Melanoma of Skin Stage III, Malignant Melanoma of Skin Stage IV
- What is being tested?
- arm 1: DC Vaccine + RT, arm 2: DC Vaccine + IFN-alfa and arm 3: both arm 1 and 2 + RT
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteItaly
- Study dates
- 8 Oct 2013to 20 Jun 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed Written Informed Consent: patients must be willing and able to give written informed consent, that have to be given before starting of screening procedure.
- Availability of autologous tumor tissue fulfilling acceptance criteria prescribed by the "Product Specification File".
- Patients must have histologically or cytologically confirmed malignant unresectable stage III or stage IV melanoma;
- Patients must have a minimum of two lesions, one of which must be measurable,(i.e. that can be accurately measured in two perpendicular dimensions, with at least 1 diameter >20 mm and the other dimension >10 mm with conventional techniques or at least 10 x 10 mm with spiral CT scan).
- Patients carrying BRAF mutation-positive melanoma must have received previous Vemurafenib, unless they are not eligible or refuse the treatment.
- Patients treated with previous first line therapy must have received Ipilimumab, unless they are not eligible or refuse the treatment.
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- Pretreated brain metastases which have been clinically stable for at least 6 months and not requiring corticosteroids are allowed;
- ECOG performance status 0-1;
- Negative screening tests for HIV, HBV HCV and syphilis not older than 30 days before performing any of the GMP-regulated activities required (leukapheresis, collection of tumor biopsies to be used for tumor lysate/homogenate preparation);
- Prior lines of chemotherapy, immunotherapy or biological therapy (e.g. inhibitors of B-Raf or c-Kit, Ipilimumab, etc.) for advanced disease are allowed (patients must have lasted prior treatments at least 4 weeks before the first vaccine dose);
- Men and women aged 18-70 years.
- Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up 8 weeks after the study, in order to minimize the risk of pregnancy;
- Patients must have normal organ and marrow function as defined below:
- leukocytes >1,500/microL
- absolute neutrophil count >1,000/microL
- platelets >80,000/microL
- total bilirubin within 2 x ULN
- AST(SGOT)/ALT(SGPT) <2.5 x ULN
- creatinine ≤ 2 mg/dl
Who cannot join
- Patients who have positive tests to HCV, HBV, HIV, or syphilis (specific blood testing must be performed within 30 days before any GMP-regulated activity (leukapheresis and collection of tumor biopsies to be used for tumor lysate/homogenate preparation).
- Patients with unresectable or metastatic melanoma BRAF V600 mutation-positive eligible to Vemurafenib cannot be enrolled in first line, unless they refuse this treatment.
- Patients eligible for Ipilimumab treatment, cannot be enrolled unless they refuse this treatment.
- Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
- Patients with known progressing and/or symptomatic brain metastases.
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- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements (on physician's judgment).
- Other known malignant neoplastic diseases in the patient's medical history with a disease-free interval of less than 3 years (except for previously treated basal cell carcinoma and in situ carcinoma of the uterine cervix);
- Any contraindication to undergo leukapheresis as evaluated by transfusionist (e.g. severe anemia, piastrinopenia, oral anticoagulant therapy).
Trial locations and contacts
1 site in 1 country.
About this study
Title: Vaccination with autologous dendritic cells loaded with autologous tumor lysate or homogenate combined with immunomodulating radiotherapy and/or preleukapheresis IFN-alfa in patients with metastatic melanoma: a randomized "proof-of-principle" phase II study.
Study Design: Randomized selection design, proof of principle study Study Duration: 36 months Number of Subjects: 24 evaluable patients
Read more
Diagnosis and Main Inclusion Criteria: Patients with non resectable stage III or stage IV malignant melanoma carrying at least 2 measurable lesions, any line after 1st line Vemurafenib in patients carrying BRAF mutation-positive melanoma and/or ≥ 2nd line Ipilimumab.
Study Product, Dose, Route, Regimen and duration of administration:
Intradermal Autologous Dendritic Cell vaccine loaded with autologous tumor lysate or homogenate on weeks 1, 4 6 and 8 during induction phase, and every 4 weeks during maintenance phase up to a maximum of 14 vaccine doses (each dose followed by IL-2 3 MU day 2-6) COMBINED OR NOT WITH
- IFN-alfa 3 MU daily for 7 days before leukapheresis AND/OR
- Three daily doses of 8 Gy up to 12 Gy delivered to one metastatic field between vaccine doses 1 and 2 (optional to one additional field between doses 7 and 8) utilizing IMRT-IMAT techniques.
Read the detailed description
Title: Vaccination with autologous dendritic cells loaded with autologous tumor lysate or homogenate combined with immunomodulating radiotherapy and/or preleukapheresis IFN-alfa in patients with metastatic melanoma: a randomized "proof-of-principle" phase II study.
Short Title/Acronym: ABSIDE (ABScopal effect-Interferon alpha-DEndritic cells)
Protocol Code IRST172.02
Phase: phase II clinical trial
Study Design: Randomized selection design, proof of principle study
Study Duration: 36 months
Study Center(s): Monocentric (IRCCS IRST Meldola)
Objectives:
Primary objectives
- Safety assessments: to determine the safety of the autologous tumor lysate loaded DC vaccine in combination with IFN-alfa and/or radiotherapy in patients with advanced melanoma.
- Clinical objective: to select the regimen that has the best immune related Disease Control Rate (irDCR) in the different external immunostimulant conditions utilized in combinations with autologous tumor lysate loaded DC vaccine.
- Immunological objective: to compare between the different treatment arms the immunologic efficacy, defined as the proportion of subjects developing positive DTH to ATL and/or KLH, combined with quantification of tumor antigen-specific circulating immune effectors performed by IFNalfa-ELISPOT analysis at the base line and after at least 4 immunizations, if DTH analysis will not detect differences in terms of immunologic efficacy between the different arms.
Number of Subjects: 24 evaluable patients
Diagnosis and Main Inclusion Criteria: Patients with non resectable stage III or stage IV malignant melanoma carrying at least 2 measurable lesions, any line after 1st line Vemurafenib in patients carrying BRAF mutation-positive melanoma and/or ≥ 2nd line Ipilimumab.
Study Product, Dose, Route, Regimen and duration of administration:
Intradermal Autologous Dendritic Cell vaccine loaded with autologous tumor lysate or homogenate on weeks 1, 4 6 and 8 during induction phase, and every 4 weeks during maintenance phase up to a maximum of 14 vaccine doses (each dose followed by IL-2 3 MU day 2-6) COMBINED OR NOT WITH
- IFN-alfa 3 MU daily for 7 days before leukapheresis AND/OR
- Three daily doses of 8 Gy up to 12 Gy delivered to one metastatic field between vaccine doses 1 and 2 (optional to one additional field between doses 7 and 8) utilizing IMRT-IMAT techniques.
Statistical Methodology: The RANDOMIZED SELECTION DESIGN was chosen basing on the assumption that immunotherapy is expected to be effective only in patients showing efficient induction of antitumor immune responses ("targeted endpoint"), allowing to reduce the number of patients required to evaluate the potential efficacy of an experimental treatment.
The Steinberg and Venzon approach will be employed to select one among different treatment arms as being worthy of further evaluation. This method requires that an adequate gap in the number of responses among different arms be observed in order to limit the probability that the selected arm is actually inferior by more than an indifferent amount. Assuming an error probability of selecting inferior arm pW =10%, with 6 patients per arm, regardless of proportion of irOR expected in each arm, the gap of 2, the largest minimal difference in the number of irOR which must be observed in order to select the arm with the higher number of irOR, provides that difference between highest probability of response and the maximum on the remaining arms is 15%. Therefore, outcomes of at least 4/6 versus the maximum on the remaining 3 arms of 2/6, at least 5/6 versus the maximum on the remaining 3 arms of 3/6 and so forth will lead to selection the most promising arm on the basis of irOR. with an error probability of 10% Otherwise no treatment arm could be considered better than others.
- Being tested
- arm 1: DC Vaccine + RT, arm 2: DC Vaccine + IFN-alfa, arm 3: both arm 1 and 2 + RT, arm 4: DC Vaccine
- Keywords
- Malignant melanoma stage III or IV, pretreated melanoma, vaccination, autologous dendritic cells, autologous tumor lysate or homogenate, immunomodulating radiotherapy
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
arm 1: DC Vaccine + RTOther
Also called vaccine + radiotherapy
three daily doses of 8 Gy up to 12 Gy delivered to one non-index metastatic field between vaccine doses 1 and 2 (optional to one additional field between vaccine doses 7 and 8) utilizing IMRT-IMAT techniques
arm 2: DC Vaccine + IFN-alfaOther
Also called vaccine + drug
daily 3 MU subcutaneous IFN-alfa for 7 days before leukapheresis (day -15 to -9, and for 7 days before any other additional leukapheresis)
arm 3: both arm 1 and 2 + RTOther
Also called vaccine + radiotherapy + drug
both 1 and 2 external immunostimulant conditions (Intradermal Autologous Dendritic Cell Vaccine + 3 single boosts of RT + IFN-alfa, 3 MU daily for 7 days before leukapheresis)
arm 4: DC VaccineBiological
Also called vaccine
neither 1 or 2 external immunostimulant conditions (only Intradermal Autologous Dendritic Cell Vaccine)
| Study group | Role | What they receive |
|---|---|---|
| arm 1: DC Vaccine + RT | Experimental | three daily doses of 8 Gy up to 12 Gy delivered to one non-index metastatic field between vaccine doses 1 and 2 (optional to one additional field between vaccine doses 7 and 8) utilizing IMRT-IMAT techniques Receives: Other: arm 1: DC Vaccine + RT |
| arm 2: DC Vaccine + IFN-alfa | Experimental | daily 3 MU subcutaneous IFN-alfa for 7 days before leukapheresis (day -15 to -9, and for 7 days before any other additional leukapheresis) Receives: Other: arm 2: DC Vaccine + IFN-alfa |
| arm 3: both arm 1 and 2 + RT | Experimental | both 1 and 2 external immunostimulant conditions (Intradermal Autologous Dendritic Cell Vaccine + 3 single boosts of RT + IFN-alfa, 3 MU daily for 7 days before leukapheresis) Receives: Other: arm 3: both arm 1 and 2 + RT |
| arm 4: DC Vaccine | Experimental | neither 1 or 2 external immunostimulant conditions (only Intradermal Autologous Dendritic Cell Vaccine) Receives: Biological: arm 4: DC Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety, tolerability and feasibility assessments
Evaluation of safety, tolerability and feasibility of the experimental treatments through the determination of the percentage of patients in each treatment group reporting an AE up to 30 days after vaccination.
Measured: 36 months
immune related Disease Control Rate (irDCR)
The irDCR, defined as the proportion of subjects showing irBOR (immuno-related Best Overall Response) of confirmed irCR (immuno-related Complete Response), irPR (immuno-related Partial Response), or irSD (immuno-related Stable Disease), will be compared in the different treatment arms, with the aim to select the most effective treatment combination.
Measured: 36 months
immunologic efficacy
The immunologic efficacy will be evaluated through DTH (Delayed Type Hypersensitivity) and IFN-gamma ELISPOT analysis of circulating antitumor effectors, after at least 4 induction doses of vaccination.
Measured: 36 months
Secondary outcomes (9)
biological effects of preleukapheresis IFN-alfa on DC (Dendritic Cells) yield
DC yield will be evaluated as the number of vaccinating DC obtained per ml of leukapheretically processed blood from each leukapheresis.
Measured: 36 months
Overall Survival (OS)
OS is defined by median survival and survival rates at 1 and 2 year of follow-up) and will be compared in the different treatment arms
Measured: 36 months
immuno-related Time To Progression (irTTP)
irTTP is the time from randomization to the first date of documented irPD (immuno-related Progressive Disease) or death and will be compared in the different treatment arms
Measured: 36 months
immuno-related Overall Response Rate (irORR)
irORR is the proportion of treated subjects with a irBOR (immuno-related Best Overall Response) of confirmed irCR (immuno-related Complete Response) or confirmed irPR (immuno-related Partial Response). It will be compared in the different treatment arms.
Measured: 36 months
immuno-related Duration of Response (irDOR)
irDOR is defined as the time between the date of the first irCR (immuno-related Complete Response) or irPR (immuno-related Partial Response) and the date of irPD (immuno-related Progressive Disease) or death. It will be compared in the different treatment arms.
Measured: 36 months
immuno-related Time To Response (irTTR)
irTTR is defined as the time from first dosing date until the first irPR (immuno-related Partial Response) or irCR (immuno-related Complete Response). It will be compared in the different treatment arms.
Measured: 36 months
immuno-related Progression free Survival (irPFS)
irPFS is defined as the time between the first dosing date and the date of irPD (immuno-related Progressive Disease), or date of death. It will be compared in the different treatment arms.
Measured: 36 months
biological effects of preleukapheresis IFN-alfa on DC (Dendritic Cells) potency
DC potency will be evaluated by a validated assay measuring the costimulatory ability of the vaccine (ELISPOT-COSTIM assay).
Measured: 36 months
biological effects of preleukapheresis IFN-alfa on TEM-8 upregulation at the mRNA level upon DC (Dendritic Cells) maturation
TEM-8 upregulation at the mRNA level upon DC maturation will be investigated by flow cytometry and real-time PCR.
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2013 (estimated)
- Study start8 Oct 2013
- Primary completion30 Sep 2023
- Study completion20 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant Melanoma of Skin Stage IIIStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Massimo Guidoboni, MD, Principal investigator, IRST IRCCS, Meldola
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01973322
- Sponsor's protocol ID
- IRST172.02
- Other IDs
- 2012-001410-41
- Acronym
- ABSIDE
- Status last verified
- Jan 2025
- First submitted
- 21 Oct 2013
- Last updated
- 9 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vaccination With Autologous Dendritic Cells Loaded With Autologous Tumor Lysate or Homogenate Combined With Immunomodulating Radiotherapy and/or Preleukapheresis IFN-alfa in Patients With Metastatic Melanoma: a Randomized "Proof-of-principle" Phase II Study
- ClinicalTrials.gov ID
- NCT01973322
- Acronym / sponsor ID
- ABSIDE / IRST172.02
- Keywords
- Malignant melanoma stage III or IV, pretreated melanoma, vaccination, autologous dendritic cells, autologous tumor lysate or homogenate, immunomodulating radiotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCSUniversity, hospital or other
- Study start
- 8 Oct 2013 (actual)
- Primary completion
- 30 Sep 2023 (actual)
- Study completion
- 20 Jun 2024 (actual)
- First posted
- 31 Oct 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.
Title: Vaccination with autologous dendritic cells loaded with autologous tumor lysate or homogenate combined with immunomodulating radiotherapy and/or preleukapheresis IFN-alfa in patients with metastatic melanoma: a randomized "proof-of-principle" phase II study.
Study Design: Randomized selection design, proof of principle study Study Duration: 36 months Number of Subjects: 24 evaluable patients
Diagnosis and Main Inclusion Criteria: Patients with non resectable stage III or stage IV malignant melanoma carrying at least 2 measurable lesions, any line after 1st line Vemurafenib in patients carrying BRAF mutation-positive melanoma and/or ≥ 2nd line Ipilimumab.
Study Product, Dose, Route, Regimen and duration of administration:
Intradermal Autologous Dendritic Cell vaccine loaded with autologous tumor lysate or homogenate on weeks 1, 4 6 and 8 during induction phase, and every 4 weeks during maintenance phase up to a maximum of 14 vaccine doses (each dose followed by IL-2 3 MU day 2-6) COMBINED OR NOT WITH
- IFN-alfa 3 MU daily for 7 days before leukapheresis AND/OR
- Three daily doses of 8 Gy up to 12 Gy delivered to one metastatic field between vaccine doses 1 and 2 (optional to one additional field between doses 7 and 8) utilizing IMRT-IMAT techniques.
Detailed description
Title: Vaccination with autologous dendritic cells loaded with autologous tumor lysate or homogenate combined with immunomodulating radiotherapy and/or preleukapheresis IFN-alfa in patients with metastatic melanoma: a randomized "proof-of-principle" phase II study.
Short Title/Acronym: ABSIDE (ABScopal effect-Interferon alpha-DEndritic cells)
Protocol Code IRST172.02
Phase: phase II clinical trial
Study Design: Randomized selection design, proof of principle study
Study Duration: 36 months
Study Center(s): Monocentric (IRCCS IRST Meldola)
Objectives:
Primary objectives
- Safety assessments: to determine the safety of the autologous tumor lysate loaded DC vaccine in combination with IFN-alfa and/or radiotherapy in patients with advanced melanoma.
- Clinical objective: to select the regimen that has the best immune related Disease Control Rate (irDCR) in the different external immunostimulant conditions utilized in combinations with autologous tumor lysate loaded DC vaccine.
- Immunological objective: to compare between the different treatment arms the immunologic efficacy, defined as the proportion of subjects developing positive DTH to ATL and/or KLH, combined with quantification of tumor antigen-specific circulating immune effectors performed by IFNalfa-ELISPOT analysis at the base line and after at least 4 immunizations, if DTH analysis will not detect differences in terms of immunologic efficacy between the different arms.
Number of Subjects: 24 evaluable patients
Diagnosis and Main Inclusion Criteria: Patients with non resectable stage III or stage IV malignant melanoma carrying at least 2 measurable lesions, any line after 1st line Vemurafenib in patients carrying BRAF mutation-positive melanoma and/or ≥ 2nd line Ipilimumab.
Study Product, Dose, Route, Regimen and duration of administration:
Intradermal Autologous Dendritic Cell vaccine loaded with autologous tumor lysate or homogenate on weeks 1, 4 6 and 8 during induction phase, and every 4 weeks during maintenance phase up to a maximum of 14 vaccine doses (each dose followed by IL-2 3 MU day 2-6) COMBINED OR NOT WITH
- IFN-alfa 3 MU daily for 7 days before leukapheresis AND/OR
- Three daily doses of 8 Gy up to 12 Gy delivered to one metastatic field between vaccine doses 1 and 2 (optional to one additional field between doses 7 and 8) utilizing IMRT-IMAT techniques.
Statistical Methodology: The RANDOMIZED SELECTION DESIGN was chosen basing on the assumption that immunotherapy is expected to be effective only in patients showing efficient induction of antitumor immune responses ("targeted endpoint"), allowing to reduce the number of patients required to evaluate the potential efficacy of an experimental treatment.
The Steinberg and Venzon approach will be employed to select one among different treatment arms as being worthy of further evaluation. This method requires that an adequate gap in the number of responses among different arms be observed in order to limit the probability that the selected arm is actually inferior by more than an indifferent amount. Assuming an error probability of selecting inferior arm pW =10%, with 6 patients per arm, regardless of proportion of irOR expected in each arm, the gap of 2, the largest minimal difference in the number of irOR which must be observed in order to select the arm with the higher number of irOR, provides that difference between highest probability of response and the maximum on the remaining arms is 15%. Therefore, outcomes of at least 4/6 versus the maximum on the remaining 3 arms of 2/6, at least 5/6 versus the maximum on the remaining 3 arms of 3/6 and so forth will lead to selection the most promising arm on the basis of irOR. with an error probability of 10% Otherwise no treatment arm could be considered better than others.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| arm 1: DC Vaccine + RT | Experimental | Other: arm 1: DC Vaccine + RTthree daily doses of 8 Gy up to 12 Gy delivered to one non-index metastatic field between vaccine doses 1 and 2 (optional to one additional field between vaccine doses 7 and 8) utilizing IMRT-IMAT techniques |
| arm 2: DC Vaccine + IFN-alfa | Experimental | Other: arm 2: DC Vaccine + IFN-alfadaily 3 MU subcutaneous IFN-alfa for 7 days before leukapheresis (day -15 to -9, and for 7 days before any other additional leukapheresis) |
| arm 3: both arm 1 and 2 + RT | Experimental | Other: arm 3: both arm 1 and 2 + RTboth 1 and 2 external immunostimulant conditions (Intradermal Autologous Dendritic Cell Vaccine + 3 single boosts of RT + IFN-alfa, 3 MU daily for 7 days before leukapheresis) |
| arm 4: DC Vaccine | Experimental | Biological: arm 4: DC Vaccineneither 1 or 2 external immunostimulant conditions (only Intradermal Autologous Dendritic Cell Vaccine) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Signed Written Informed Consent: patients must be willing and able to give written informed consent, that have to be given before starting of screening procedure.
- Availability of autologous tumor tissue fulfilling acceptance criteria prescribed by the "Product Specification File".
- Patients must have histologically or cytologically confirmed malignant unresectable stage III or stage IV melanoma;
- Patients must have a minimum of two lesions, one of which must be measurable,(i.e. that can be accurately measured in two perpendicular dimensions, with at least 1 diameter >20 mm and the other dimension >10 mm with conventional techniques or at least 10 x 10 mm with spiral CT scan).
- Patients carrying BRAF mutation-positive melanoma must have received previous Vemurafenib, unless they are not eligible or refuse the treatment.
Key exclusion criteria (9 listed)
- Patients who have positive tests to HCV, HBV, HIV, or syphilis (specific blood testing must be performed within 30 days before any GMP-regulated activity (leukapheresis and collection of tumor biopsies to be used for tumor lysate/homogenate preparation).
- Patients with unresectable or metastatic melanoma BRAF V600 mutation-positive eligible to Vemurafenib cannot be enrolled in first line, unless they refuse this treatment.
- Patients eligible for Ipilimumab treatment, cannot be enrolled unless they refuse this treatment.
- Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
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 |
|---|---|---|
| arm 1: DC Vaccine + RTAlso: vaccine + radiotherapythree daily doses of 8 Gy up to 12 Gy delivered to one non-index metastatic field between vaccine doses 1 and 2 (optional to one additional field between vaccine doses 7 and 8) utilizing IMRT-IMAT techniques | Other | arm 1: DC Vaccine + RT |
| arm 2: DC Vaccine + IFN-alfaAlso: vaccine + drugdaily 3 MU subcutaneous IFN-alfa for 7 days before leukapheresis (day -15 to -9, and for 7 days before any other additional leukapheresis) | Other | arm 2: DC Vaccine + IFN-alfa |
| arm 3: both arm 1 and 2 + RTAlso: vaccine + radiotherapy + drugboth 1 and 2 external immunostimulant conditions (Intradermal Autologous Dendritic Cell Vaccine + 3 single boosts of RT + IFN-alfa, 3 MU daily for 7 days before leukapheresis) | Other | arm 3: both arm 1 and 2 + RT |
| arm 4: DC VaccineAlso: vaccineneither 1 or 2 external immunostimulant conditions (only Intradermal Autologous Dendritic Cell Vaccine) | Biological | arm 4: DC Vaccine |
Primary outcome
Safety, tolerability and feasibility assessments
Time frame: 36 months
Evaluation of safety, tolerability and feasibility of the experimental treatments through the determination of the percentage of patients in each treatment group reporting an AE up to 30 days after vaccination.
immune related Disease Control Rate (irDCR)
Time frame: 36 months
The irDCR, defined as the proportion of subjects showing irBOR (immuno-related Best Overall Response) of confirmed irCR (immuno-related Complete Response), irPR (immuno-related Partial Response), or irSD (immuno-related Stable Disease), will be compared in the different treatment arms, with the aim to select the most effective treatment combination.
immunologic efficacy
Time frame: 36 months
The immunologic efficacy will be evaluated through DTH (Delayed Type Hypersensitivity) and IFN-gamma ELISPOT analysis of circulating antitumor effectors, after at least 4 induction doses of vaccination.
9 secondary outcomes
biological effects of preleukapheresis IFN-alfa on DC (Dendritic Cells) yield
Time frame: 36 months
Overall Survival (OS)
Time frame: 36 months
immuno-related Time To Progression (irTTP)
Time frame: 36 months
immuno-related Overall Response Rate (irORR)
Time frame: 36 months
immuno-related Duration of Response (irDOR)
Time frame: 36 months
immuno-related Time To Response (irTTR)
Time frame: 36 months
immuno-related Progression free Survival (irPFS)
Time frame: 36 months
biological effects of preleukapheresis IFN-alfa on DC (Dendritic Cells) potency
Time frame: 36 months
biological effects of preleukapheresis IFN-alfa on TEM-8 upregulation at the mRNA level upon DC (Dendritic Cells) maturation
Time frame: 36 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2025.
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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. This study is not recruiting at the moment.
Massimo Guidoboni, MD principal investigator
IRST IRCCS, Meldola
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing arm 1: DC Vaccine + RT, arm 2: DC Vaccine + IFN-alfa and arm 3: both arm 1 and 2 + RT in people with Malignant Melanoma of Skin Stage III and Malignant Melanoma of Skin Stage IV, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 1 site in Italy.
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 19 inclusion and 9 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: finished, as of the sponsor's last update on 9 Jan 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 Italy. 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 phase mean?
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety, tolerability and feasibility assessments (time frame: 36 months). The study lists 3 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 9 Jan 2025.