Ignite Creation Date:
2024-05-06 @ 2:07 AM
Last Modification Date:
2024-10-26 @ 11:14 AM
Study NCT ID:
NCT01973322
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2021-02-26
First Post:
2013-10-21
Brief Title:
Vaccination With Autologous Dendritic Cells Loaded With Autologous Tumor Lysate or Homogenate Combined With Immunomodulating Radiotherapy andor Preleukapheresis IFN-alfa in Patients With Metastatic Melanoma a Randomized Proof-of-principle Phase II Study
Sponsor:
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Organization:
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Study Overview
Official Title:
Vaccination With Autologous Dendritic Cells Loaded With Autologous Tumor Lysate or Homogenate Combined With Immunomodulating Radiotherapy andor Preleukapheresis IFN-alfa in Patients With Metastatic Melanoma a Randomized Proof-of-principle Phase II Study
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ABSIDE
Brief Summary:
Title Vaccination with autologous dendritic cells loaded with autologous tumor lysate or homogenate combined with immunomodulating radiotherapy andor 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 andor 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 ANDOR
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
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 andor 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 ANDOR
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 andor preleukapheresis IFN-alfa in patients with metastatic melanoma a randomized proof-of-principle phase II study
Short TitleAcronym ABSIDE ABScopal effect-Interferon alpha-DEndritic cells
Protocol Code IRST17202
Phase phase II clinical trial
Study Design Randomized selection design proof of principle study
Study Duration 36 months
Study Centers Monocentric IRCCS IRST Meldola
Objectives
Primary objectives
1 Safety assessments to determine the safety of the autologous tumor lysate loaded DC vaccine in combination with IFN-alfa andor radiotherapy in patients with advanced melanoma
2 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
3 Immunological objective to compare between the different treatment arms the immunologic efficacy defined as the proportion of subjects developing positive DTH to ATL andor 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 andor 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 ANDOR
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 46 versus the maximum on the remaining 3 arms of 26 at least 56 versus the maximum on the remaining 3 arms of 36 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
Short TitleAcronym ABSIDE ABScopal effect-Interferon alpha-DEndritic cells
Protocol Code IRST17202
Phase phase II clinical trial
Study Design Randomized selection design proof of principle study
Study Duration 36 months
Study Centers Monocentric IRCCS IRST Meldola
Objectives
Primary objectives
1 Safety assessments to determine the safety of the autologous tumor lysate loaded DC vaccine in combination with IFN-alfa andor radiotherapy in patients with advanced melanoma
2 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
3 Immunological objective to compare between the different treatment arms the immunologic efficacy defined as the proportion of subjects developing positive DTH to ATL andor 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 andor 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 ANDOR
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 46 versus the maximum on the remaining 3 arms of 26 at least 56 versus the maximum on the remaining 3 arms of 36 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2012-001410-41 | EUDRACT_NUMBER | None | None |