Ignite Creation Date:
2025-12-24 @ 9:31 PM
Ignite Modification Date:
2026-01-05 @ 6:23 PM
Study NCT ID:
NCT03063632
Status:
COMPLETED
Last Update Posted:
2023-10-25
First Post:
2017-02-22
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Testing the Combination of Two Experimental Drugs MK-3475 (Pembrolizumab) and Interferon-gamma for the Treatment of Mycosis Fungoides and Sézary Syndrome and Advanced Synovial Sarcoma
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase II Trial of MK-3475 (Pembrolizumab) and Interferon Gamma 1-b Combination Immunotherapy in Patients With Previously Treated Mycosis Fungoides and Sezary Syndrome (Treatment Group 1) and in Patients With Advanced Synovial Sarcoma (Treatment Group 2)
Status:
COMPLETED
Status Verified Date:
2023-10
Last Known Status:
None
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:
None
Brief Summary:
This phase II trial studies how well pembrolizumab and interferon gamma-1b work in treating patients with stage IB-IVB mycosis fungoides and Sezary syndrome that has come back (relapsed) or has not responded to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Interferon gamma-1b may boost the immune system activity. Giving pembrolizumab and interferon gamma-1b together may work better in treating patients with stage IB-IVB mycosis fungoides and Sezary syndrome.
Detailed Description:
PRIMARY OBJECTIVES:
I. To assess the overall response rate (ORR) of MK-3475 (pembrolizumab) and interferon gamma-1b (IFN-G) (Actimmune) combination immunotherapy in subjects with previously treated mycosis fungoides or Sezary syndrome. (Treatment Group 1) II. To determine whether the combination of interferon gamma-1b (ACTIMMUNE) and MK-3475 (pembrolizumab) improves the ORR of pembrolizumab in patients with unresectable or metastatic synovial sarcoma. (Treatment Group 2)
SECONDARY OBJECTIVES:
I. To explore the safety/tolerability and clinical activity of MK-3475 (pembrolizumab) and IFN-G (Actimmune) in subjects with previously treated mycosis fungoides or Sezary syndrome with respect to (Treatment Group 1):
Ia. Safety and tolerability. Ib. Time to response (TTR). Ic. Duration of response (DOR). Id. Progression-free survival (PFS). Ie. Event-free survival (EFS). If. Percentage of all patients who have a response duration of at least 12 months (ORR12).
II. To determine the progression-free survival (PFS) and overall survival (OS) for patients with advanced synovial sarcoma receiving interferon gamma-1b and MK-3475 (pembrolizumab). (Treatment Group 2) III. To determine the tolerability of the combination of interferon gamma-1b and MK-3475 (pembrolizumab) based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. (Treatment Group 2)
EXPLORATORY OBJECTIVES:
I. To investigate the relationship between the following putative biomarkers for combination immunotherapy of MK-3475 pembrolizumab) and IFN-gamma (Actimmune) and clinical outcomes (as measured by safety/tolerability and ORR, DOR, PFS, EFS) in subjects with previously treated mycosis fungoides or Sezary syndrome, including tumor/microenvironment (PD-1/PD-L1/PD-L2 expression, cytotoxic T lymphocyte \[CTL\]s, regulatory T cell \[Treg\]s, macrophages, dendritic cell \[DC\]s; nanostring gene expression profile), systemic immune response (flow cytometry, mass cytometry \[CyTOF\], Luminex multiplexed cytokine profile), and molecular/genomic immune correlates (exome sequencing, high throughput sequencing \[HTS\] for T cell receptor \[TCR\]). (Treatment Group 1)
II. To investigate paired, serial biopsy specimens from pre-treatment and 8-12 weeks after starting treatment for the following (Treatment Group 2):
IIa. MHC class I expression (scored by pathologist). IIb. Number of infiltrating T cells per mm\^2. IIc. Tumor associated macrophage number and phenotype using multiplex immunohistochemistry.
IId. T cell clonality. IIe. Gene expression profiling.
III. To investigate peripheral blood samples from patients to determine (Treatment Group 2):
IIIa. The number and phenotype of T cells specific for computed tomography (CT) antigens and potential neo-antigens.
IIb. The phenotype and activation state of circulating monocytes and peripheral blood mononuclear cell (PBMC).
IIc. Cytokines associated with response.
OUTLINE: Patients are assigned to 1 of 2 groups.
GROUP I: Patients with Mycosis Fungoides and Sezary Syndrome receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 3 weeks for up to 2 years in the absence of disease progression or unexpected toxicity. Patients also receive interferon gamma-1b subcutaneously (SC) 3 times per week for 12 weeks, and then follow 3 weeks on and 3 weeks off schedule for up to 2 years in the absence of disease progression or unexpected toxicity.
GROUP II: Patients with advanced synovial sarcoma receive pembrolizumab IV over 30 minutes on day 1 and interferon gamma-1b SC once a week. Cycles repeat every 3 weeks for up to 2 years in the absence of disease progression or unexpected toxicity.
After completion of study treatment, patients are followed up for 30 days and then every 12 weeks for up to 1 year.
I. To assess the overall response rate (ORR) of MK-3475 (pembrolizumab) and interferon gamma-1b (IFN-G) (Actimmune) combination immunotherapy in subjects with previously treated mycosis fungoides or Sezary syndrome. (Treatment Group 1) II. To determine whether the combination of interferon gamma-1b (ACTIMMUNE) and MK-3475 (pembrolizumab) improves the ORR of pembrolizumab in patients with unresectable or metastatic synovial sarcoma. (Treatment Group 2)
SECONDARY OBJECTIVES:
I. To explore the safety/tolerability and clinical activity of MK-3475 (pembrolizumab) and IFN-G (Actimmune) in subjects with previously treated mycosis fungoides or Sezary syndrome with respect to (Treatment Group 1):
Ia. Safety and tolerability. Ib. Time to response (TTR). Ic. Duration of response (DOR). Id. Progression-free survival (PFS). Ie. Event-free survival (EFS). If. Percentage of all patients who have a response duration of at least 12 months (ORR12).
II. To determine the progression-free survival (PFS) and overall survival (OS) for patients with advanced synovial sarcoma receiving interferon gamma-1b and MK-3475 (pembrolizumab). (Treatment Group 2) III. To determine the tolerability of the combination of interferon gamma-1b and MK-3475 (pembrolizumab) based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. (Treatment Group 2)
EXPLORATORY OBJECTIVES:
I. To investigate the relationship between the following putative biomarkers for combination immunotherapy of MK-3475 pembrolizumab) and IFN-gamma (Actimmune) and clinical outcomes (as measured by safety/tolerability and ORR, DOR, PFS, EFS) in subjects with previously treated mycosis fungoides or Sezary syndrome, including tumor/microenvironment (PD-1/PD-L1/PD-L2 expression, cytotoxic T lymphocyte \[CTL\]s, regulatory T cell \[Treg\]s, macrophages, dendritic cell \[DC\]s; nanostring gene expression profile), systemic immune response (flow cytometry, mass cytometry \[CyTOF\], Luminex multiplexed cytokine profile), and molecular/genomic immune correlates (exome sequencing, high throughput sequencing \[HTS\] for T cell receptor \[TCR\]). (Treatment Group 1)
II. To investigate paired, serial biopsy specimens from pre-treatment and 8-12 weeks after starting treatment for the following (Treatment Group 2):
IIa. MHC class I expression (scored by pathologist). IIb. Number of infiltrating T cells per mm\^2. IIc. Tumor associated macrophage number and phenotype using multiplex immunohistochemistry.
IId. T cell clonality. IIe. Gene expression profiling.
III. To investigate peripheral blood samples from patients to determine (Treatment Group 2):
IIIa. The number and phenotype of T cells specific for computed tomography (CT) antigens and potential neo-antigens.
IIb. The phenotype and activation state of circulating monocytes and peripheral blood mononuclear cell (PBMC).
IIc. Cytokines associated with response.
OUTLINE: Patients are assigned to 1 of 2 groups.
GROUP I: Patients with Mycosis Fungoides and Sezary Syndrome receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 3 weeks for up to 2 years in the absence of disease progression or unexpected toxicity. Patients also receive interferon gamma-1b subcutaneously (SC) 3 times per week for 12 weeks, and then follow 3 weeks on and 3 weeks off schedule for up to 2 years in the absence of disease progression or unexpected toxicity.
GROUP II: Patients with advanced synovial sarcoma receive pembrolizumab IV over 30 minutes on day 1 and interferon gamma-1b SC once a week. Cycles repeat every 3 weeks for up to 2 years in the absence of disease progression or unexpected toxicity.
After completion of study treatment, patients are followed up for 30 days and then every 12 weeks for up to 1 year.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2017-00265 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| CITN-13 | None | None | View | |
| CITN-13 | OTHER | Cancer Immunotherapy Trials Network | View | |
| CITN-13 | OTHER | CTEP | View | |
| P30CA015704 | NIH | None | https://reporter.nih.gov/quic… | View |
| U01CA154967 | NIH | None | https://reporter.nih.gov/quic… | View |