Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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 (ABSIDE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01973322
Recruitment Status : Recruiting
First Posted : October 31, 2013
Last Update Posted : November 9, 2018
Sponsor:
Information provided by (Responsible Party):
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Brief 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.

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.

Condition or disease Intervention/treatment Phase
Malignant Melanoma of Skin Stage III Malignant Melanoma of Skin Stage IV Other: arm 1: DC Vaccine + RT Other: arm 2: DC Vaccine + IFN-alfa Other: arm 3: both arm 1 and 2 + RT Biological: arm 4: DC Vaccine Phase 2

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 8, 2013
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: arm 1: DC Vaccine + RT
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
Other: arm 1: DC Vaccine + RT
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
Other Name: vaccine + radiotherapy

Experimental: arm 2: DC Vaccine + IFN-alfa
daily 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
daily 3 MU subcutaneous IFN-alfa for 7 days before leukapheresis (day -15 to -9, and for 7 days before any other additional leukapheresis)
Other Name: vaccine + drug

Experimental: arm 3: both arm 1 and 2 + RT
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)
Other: arm 3: both arm 1 and 2 + RT
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)
Other Name: vaccine + radiotherapy + drug

Experimental: arm 4: DC Vaccine
neither 1 or 2 external immunostimulant conditions (only Intradermal Autologous Dendritic Cell Vaccine)
Biological: arm 4: DC Vaccine
neither 1 or 2 external immunostimulant conditions (only Intradermal Autologous Dendritic Cell Vaccine)
Other Name: vaccine




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. biological effects of preleukapheresis IFN-alfa on DC (Dendritic Cells) yield [ Time Frame: 36 months ]
    DC yield will be evaluated as the number of vaccinating DC obtained per ml of leukapheretically processed blood from each leukapheresis.

  2. Overall Survival (OS) [ Time Frame: 36 months ]
    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

  3. immuno-related Time To Progression (irTTP) [ Time Frame: 36 months ]
    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

  4. immuno-related Overall Response Rate (irORR) [ Time Frame: 36 months ]
    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.

  5. immuno-related Duration of Response (irDOR) [ Time Frame: 36 months ]
    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.

  6. immuno-related Time To Response (irTTR) [ Time Frame: 36 months ]
    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.

  7. immuno-related Progression free Survival (irPFS) [ Time Frame: 36 months ]
    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.

  8. biological effects of preleukapheresis IFN-alfa on DC (Dendritic Cells) potency [ Time Frame: 36 months ]
    DC potency will be evaluated by a validated assay measuring the costimulatory ability of the vaccine (ELISPOT-COSTIM assay).

  9. biological effects of preleukapheresis IFN-alfa on TEM-8 upregulation at the mRNA level upon DC (Dendritic Cells) maturation [ Time Frame: 36 months ]
    TEM-8 upregulation at the mRNA level upon DC maturation will be investigated by flow cytometry and real-time PCR.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. Availability of autologous tumor tissue fulfilling acceptance criteria prescribed by the "Product Specification File".
  3. Patients must have histologically or cytologically confirmed malignant unresectable stage III or stage IV melanoma;
  4. 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).
  5. Patients carrying BRAF mutation-positive melanoma must have received previous Vemurafenib, unless they are not eligible or refuse the treatment.
  6. Patients treated with previous first line therapy must have received Ipilimumab, unless they are not eligible or refuse the treatment.
  7. Pretreated brain metastases which have been clinically stable for at least 6 months and not requiring corticosteroids are allowed;
  8. ECOG performance status 0-1;
  9. 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);
  10. 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);
  11. Men and women aged 18-70 years.
  12. 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;
  13. 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

Exclusion Criteria:

  1. 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).
  2. Patients with unresectable or metastatic melanoma BRAF V600 mutation-positive eligible to Vemurafenib cannot be enrolled in first line, unless they refuse this treatment.
  3. Patients eligible for Ipilimumab treatment, cannot be enrolled unless they refuse this treatment.
  4. 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.
  5. Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
  6. Patients with known progressing and/or symptomatic brain metastases.
  7. 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).
  8. 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);
  9. Any contraindication to undergo leukapheresis as evaluated by transfusionist (e.g. severe anemia, piastrinopenia, oral anticoagulant therapy).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01973322


Contacts
Layout table for location contacts
Contact: Oriana Nanni, PhD +390543739266 oriana.nanni@irst.emr.it

Locations
Layout table for location information
Italy
UO Immunoterapia e laboratorio TCS, IRST IRCCS Recruiting
Meldola, FC, Italy, 47014
Contact: Massimo Guidoboni, MD    +390543739100    massimo.guidoboni@irst.emr.it   
Principal Investigator: Massimo Guidoboni, MD         
Sponsors and Collaborators
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Investigators
Layout table for investigator information
Principal Investigator: Massimo Guidoboni, MD IRST IRCCS, Meldola

Layout table for additonal information
Responsible Party: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
ClinicalTrials.gov Identifier: NCT01973322     History of Changes
Other Study ID Numbers: IRST172.02
2012-001410-41 ( EudraCT Number )
First Posted: October 31, 2013    Key Record Dates
Last Update Posted: November 9, 2018
Last Verified: November 2018

Keywords provided by Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori:
Malignant melanoma stage III or IV
pretreated melanoma
vaccination
autologous dendritic cells
autologous tumor lysate or homogenate
immunomodulating radiotherapy

Additional relevant MeSH terms:
Layout table for MeSH terms
Melanoma
Skin Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms by Site
Skin Diseases
Vaccines
Complement Factor H
Interferon-alpha
Interferon alpha-2
Immunologic Factors
Physiological Effects of Drugs
Complement Inactivating Agents
Immunosuppressive Agents
Antiviral Agents
Anti-Infective Agents
Antineoplastic Agents