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Complementary Vaccination With Dendritic Cells Pulsed With Autologous Tumor Lysate in Resected Stage III and IV Melanoma Patients. (ACDC)

Primary Purpose

Malignant Melanoma, Adjuvant Drug Therapy, Vaccin Therapy

Status

Terminated

Phase

Phase 2

Locations

Italy

Study Type

Interventional

Intervention

Autologous Dendritic Cell vaccine

About this trial

This is an interventional treatment trial for Malignant Melanoma focused on measuring Intradermal Autologous Dendritic Cell Vaccine, Malignant Melanoma, Adjuvant, vaccin, therapy, randomized trial, observation

Eligibility Criteria

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

Inclusion Criteria:

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 melanoma (all type of melanomas);
Patients must be disease free after surgical removal of a metastatic lesions (stage IV or metachronous stage III)
Eastern Cooperative Oncology Group performance status 0-1
Negative screening tests for HIV, Hepatitis B virus, Hepatitis C virus and syphilis not older than 30 days before performing any of the Good Manufacturing Practice-regulated activities required (leukapheresis, collection of tumor biopsies to be used for tumor lysate/homogenate preparation);
Men and women aged ≥ 18 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 according to clinical practice.

Exclusion Criteria:

Patients who have positive tests to Hepatitis B virus, Hepatitis C virus HIV, or syphilis (specific blood testing must be performed within 30 days before any Good Manufacturing Practice-regulated activity (leukapheresis and collection of tumor biopsies to be used for tumor lysate preparation).
Patients who have had prior lines of systemic chemotherapy, immunotherapy or biological therapy for metastatic melanoma.
Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
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, thrombocytopenia, oral anticoagulant therapy) or to undergo surgery

Sites / Locations

UO Oncologia Medica, IRCCS IRST
UO Immunoterapia e laboratorio TCS, IRST IRCCS

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Arm A: Autologous Dendritic Cell vaccine

Arm B: follow up

Arm Description

Daily 3 MU Interleukin 2 will be administered subcutaneously for 5 days starting from the second day after each vaccine dose. Vaccine doses will be given intradermally in two sites close to inguinal or axillary lymphnode stations that had not site of previous surgical exeresis.The first dose (WK1) will consist of freshly prepared vaccine, whereas for all the further doses cryopreserved aliquots will be utilized. The remaining 5 doses will be administered every 4 weeks to complete six months of therapy (six vaccines).

Arm B: Patients will undergo laboratory and clinical assessment, tumor re-staging, blood collection for immunological biomarkers every 12 weeks until relapse.

Outcomes

Primary Outcome Measures

Relapse-free survival (RFS)

Secondary Outcome Measures

Overall survival (OS)

Immunologic efficacy will be measured by best delayed-type hypersensitivity score (reactivity to lysate or KLH) obtained after at least 4 vaccine doses

Full Information

NCT ID

NCT02718391

First Posted

January 21, 2016

Last Updated

April 20, 2020

Sponsor

Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

1. Study Identification

Unique Protocol Identification Number

NCT02718391

Brief Title

Complementary Vaccination With Dendritic Cells Pulsed With Autologous Tumor Lysate in Resected Stage III and IV Melanoma Patients.

Acronym

ACDC

Official Title

Complementary Vaccination With Dendritic Cells Pulsed With Autologous Tumor Lysate in Resected Stage III and IV Melanoma Patients: a Phase II Randomized Trial (ACDC Adjuvant Trial)

Study Type

Interventional

2. Study Status

Record Verification Date

April 2019

Overall Recruitment Status

Terminated

Why Stopped

The randomization to the observational arm of the trial was no longer ethical

Study Start Date

August 2015 (Actual)

Primary Completion Date

November 2019 (Actual)

Study Completion Date

November 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This phase II, randomized, open-label trial aims to assess whether the vaccination increase RFS in disease free melanoma patients after surgery. Patients will be randomized between Intradermal Autologous Dendritic Cell Vaccine loaded with autologous tumor lysate or homogenate (6 vaccines every 4 weeks) and observation.

Detailed Description

This study will be a randomized phase II trial (1:1 allocation ratio) in resected stage III/IV melanoma patients. The randomization list will be stratified by stage (III and IV M1a-b and IVM1c), and time from primitive tumor to first metastasis (≤ 2 years versus > 2 years). Five randomization lists will be defined, one for each stratum. On the basis of literature, the investigators assume a median relapse-free survival of 7.0 months for the standard group. With a two-sided tailed alpha of 0.10 and power of 80%, assuming a median relapse-free survival of 11.7 months in the experimental arm (hazard ratio 0.60), it will be necessary to recruit 60 patients per arm over a period of 24 months and to have a subsequent 12 months of follow-up. In the context of data monitoring board activities, an interim analysis for futility, according to the Bayesian approach, will be performed at 18 months in order to control the safety. Primary endpoints will be relapse free survival. Secondary end points will be OS, In vivo and in vitro immunomonitoring. Immunologic efficacy will be measured by best Delayed Type Hypersensitivity score (reactivity to lysate or KLH) obtained after at least 4 vaccine doses, alone or combined with Interferon-g ELISPOT analysis of tumor antigen-specific circulating effectors obtained after a minimum of 4 vaccine doses, both compared with prevaccine samples. In vivo monitoring will focus on functional phenotyping of circulating immune effectors/regulators, functional characterization of circulating tumor antigen-specific immune effectors and regulators, and identification of serum markers that are predictive of response.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Malignant Melanoma, Adjuvant Drug Therapy, Vaccin Therapy

Keywords

Intradermal Autologous Dendritic Cell Vaccine, Malignant Melanoma, Adjuvant, vaccin, therapy, randomized trial, observation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A: Autologous Dendritic Cell vaccine

Arm Type

Experimental

Arm Description

Arm Title

Arm B: follow up

Arm Type

No Intervention

Arm Description

Arm B: Patients will undergo laboratory and clinical assessment, tumor re-staging, blood collection for immunological biomarkers every 12 weeks until relapse.

Intervention Type

Biological

Intervention Name(s)

Autologous Dendritic Cell vaccine

Intervention Description

The Dendritic Cells vaccine is given intradermally with 5 injections in sites close to inguinal or axillary lymphnode stations that had not site of previous surgical exeresis; as a rule, vaccine administrations should be performed by alternating injections sites. Two days after each vaccine administration, daily 3 MU Interleukin 2 will be administered subcutaneously for 5 days.

Primary Outcome Measure Information:

Title

Relapse-free survival (RFS)

Time Frame

The time from the date of randomization to the date of the first relapse or the date of death from any cause or the date of the last restaging in non relapsed patients, assessed up to 36 months

Secondary Outcome Measure Information:

Title

Overall survival (OS)

Time Frame

From the date of randomization until the date of death from any cause or the last date the patient was known to be alive, assessed up to 36 months

Title

Immunologic efficacy will be measured by best delayed-type hypersensitivity score (reactivity to lysate or KLH) obtained after at least 4 vaccine doses

Time Frame

up to 36 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 melanoma (all type of melanomas); Patients must be disease free after surgical removal of a metastatic lesions (stage IV or metachronous stage III) Eastern Cooperative Oncology Group performance status 0-1 Negative screening tests for HIV, Hepatitis B virus, Hepatitis C virus and syphilis not older than 30 days before performing any of the Good Manufacturing Practice-regulated activities required (leukapheresis, collection of tumor biopsies to be used for tumor lysate/homogenate preparation); Men and women aged ≥ 18 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 according to clinical practice. Exclusion Criteria: Patients who have positive tests to Hepatitis B virus, Hepatitis C virus HIV, or syphilis (specific blood testing must be performed within 30 days before any Good Manufacturing Practice-regulated activity (leukapheresis and collection of tumor biopsies to be used for tumor lysate preparation). Patients who have had prior lines of systemic chemotherapy, immunotherapy or biological therapy for metastatic melanoma. Participation in another clinical trial with any investigational agents within 30 days prior to study screening. 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, thrombocytopenia, oral anticoagulant therapy) or to undergo surgery

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Laura Ridolfi, MD

Organizational Affiliation

IRST IRCCS

Official's Role

Principal Investigator

Facility Information:

Facility Name

UO Oncologia Medica, IRCCS IRST

City

Meldola (FC)

State/Province

ZIP/Postal Code

47014

Country

Italy

Facility Name

UO Immunoterapia e laboratorio TCS, IRST IRCCS

City

Meldola

State/Province

ZIP/Postal Code

47014

Country

Italy

12. IPD Sharing Statement

Learn more about this trial

Complementary Vaccination With Dendritic Cells Pulsed With Autologous Tumor Lysate in Resected Stage III and IV Melanoma Patients.

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