Malignant Pleural Mesothelioma
Conditions
Keywords
GM-CSF, MONTANIDE ISA 51, WT1 PEPTIDE SPECIFIC T CELLS, Vaccine, 10-134, Galinpepimut-S
Brief summary
Study of galinpepimut-S, a Wilms Tumor-1 (WT1) vaccine, to see if it delays or prevents the mesothelioma from growing back after surgery. WT1 is a protein in cancer cells that regulates gene expression and causes cell growth.
Detailed description
The doctors are testing galinpepimut-S, a Wilms Tumor-1 (WT1) vaccine, to see if it delays or prevents the mesothelioma from growing back after surgery. WT1 is a protein in cancer cells that regulates gene expression and causes cell growth. Mesothelioma tumors generally have high levels of WT1.This study was originally designed to have two treatment groups. One group received non-specific immunotherapy with medications called Montanide and Sargramostim (Granulocyte Macrophage Colony Stimulating Factor, GM-CSF). Enrollment to this group has stopped The other group, which continues receives more specific immunotherapy with galinpepimut-S plus Montanide and GM-CSF. Both Montanide and GM-CSF are commonly given along with vaccines because they have a general effect in boosting the immune response. Some researchers believe that this general increase in the immune system may have some effect in treating cancer. Some studies using GM-CSF with melanoma vaccines have suggested that it could lessen the effects of the vaccine. The addition of the WT1 proteins makes this therapy more directed to mesothelioma. The combination of galinpepimut-S with Montanide and GM-CSF has been tested in a prior trial including 9 patients with advanced mesothelioma. In that trial, the vaccine was safe and caused an immune response.
Interventions
BIOLOGICALGalinpepimut-S + Montanide + GM-CSF
Patients will receive 6 injections over 12 weeks. Treatment will be administered on weeks 0, 2, 4, 6, 8, and 10. All patients will receive Sargramostim (GM-CSF) (70 mcg) injected subcutaneously on days 0 and -2 of each vaccination. Patients may self administer the Sargramostim (GM-CSF) on day -2 if they have been appropriately instructed on SQ injection administration. Patients will be informed of the expected reactions such as irritation at the injection site. Patients will keep a logbook noting the time and placement of the injection. Patients will also receive 1.0 ml of emulsion with Montanide alone or with WT-1 peptides plus Montanide. It will be administered by a nurse (it may not be self administered) subcutaneously to the same anatomical site as the GM-CSF. This site will be marked by the patient or treating healthcare professional by a permanent marker pen.
BIOLOGICALMontanide + GM-CSF
Patients will receive 6 injections over 12 weeks. Treatment will be administered on weeks 0, 2, 4, 6, 8, and 10. All patients will receive Sargramostim (GM-CSF) (70 mcg) injected subcutaneously on days 0 and -2 of each vaccination. Patients may self administer the Sargramostim (GM-CSF) on day -2 if they have been appropriately instructed on SQ injection administration. Patients will be informed of the expected reactions such as irritation at the injection site. Patients will keep a logbook noting the time and placement of the injection. Patients will also receive 1.0 ml of emulsion with Montanide alone or with WT-1 peptides plus Montanide. It will be administered by a nurse (it may not be self-administered)subcutaneously to the same anatomical site as the GM-CSF. This site will be marked by the patient or treating healthcare professional by a permanent marker pen.
Sponsors
United States Department of Defense
Sellas Life Sciences Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologic diagnosis of malignant pleural mesothelioma (MPM) confirmed at participating institution. * Positive immunohistochemical staining for WT-1 (greater than 10% of cells). * Completion of multimodality therapy. This must include surgical resection by either pleurectomy/decortication or extrapleural pneumonectomy. The surgery should be performed with the intent of complete resection, though patients with an R1 resection will still be eligible. Patients should have also received treatment with chemotherapy and/or radiation. Patients with an R2 resection are also eligible as long as the site of residual disease is treated post-operatively with radiotherapy. * 4-12 weeks since completion of combined modality therapy. * Age \> or = to 18 years * Karnofsky performance status \> or = to 70% * Hematologic parameters: Absolute neutrophil count \> or = to 1000/mcL, Platelets \> or = to 50K/mcL. * Biochemical parameters: Total bilirubin \< or = to 2.0 mg/dl, AST and ALT \< or = to 2.5 x upper limits of normal, Creatinine \< or = to 2.0 mg/dl.
Exclusion criteria
* Pregnant or lactating women. * Patients with active infection requiring systemic antibiotics, antiviral, or antifungal treatments. * Patients with a serious unstable medical illness or another active cancer. * Patients taking systemic corticosteroids. * Patients with an immunodeficiency syndrome.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1-year Progression-free Survival | 1 year | Progression free survival (PFS) rate will be calculated from the time of randomization to first evidence of disease recurrence or death of any cause. |
| Progression-free Survival | Up to 5 years and 11 months | Median progression free survival (PFS) is where PFS are assessed from the time of randomization to first evidence of disease recurrence or death of any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immune Response | 12 weeks | Immunogenicity of galinpepimut-S and control from a subset of participants |
| Overall Survival | Uo to 5 years and 11 months | Median overall survival (OS) is estimated from time of randomization to all cause mortality |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Galinpepimut-S Galinpepimut-s + Montanide + GM-CSF | 20 |
| Control Montanide + GM-CSF | 21 |
| Total | 41 |
Baseline characteristics
| Characteristic | Galinpepimut-S | Control | Total |
|---|---|---|---|
| Age, Continuous | 70 years | 67 years | 68 years |
| Histology Epithelioid | 18 Participants | 21 Participants | 39 Participants |
| Histology Mixed | 2 Participants | 0 Participants | 2 Participants |
| Histology Sarcomatoid | 0 Participants | 0 Participants | 0 Participants |
| Karnofsky performance status at enrollment 100% | 1 Participants | 0 Participants | 1 Participants |
| Karnofsky performance status at enrollment 70% | 1 Participants | 3 Participants | 4 Participants |
| Karnofsky performance status at enrollment 80% | 7 Participants | 12 Participants | 19 Participants |
| Karnofsky performance status at enrollment 90% | 11 Participants | 6 Participants | 17 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 17 Participants | 18 Participants | 35 Participants |
| Smoking status Current | 0 Participants | 0 Participants | 0 Participants |
| Smoking status Former | 12 Participants | 13 Participants | 25 Participants |
| Smoking status Never | 8 Participants | 8 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 16 / 20 | 20 / 21 |
| other Total, other adverse events | 17 / 20 | 10 / 21 |
| serious Total, serious adverse events | 1 / 20 | 1 / 21 |
Outcome results
Primary
1-year Progression-free Survival
Progression free survival (PFS) rate will be calculated from the time of randomization to first evidence of disease recurrence or death of any cause.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Galinpepimut-S | 1-year Progression-free Survival | 44 percentage of participants |
| Control | 1-year Progression-free Survival | 33 percentage of participants |
Primary
Progression-free Survival
Median progression free survival (PFS) is where PFS are assessed from the time of randomization to first evidence of disease recurrence or death of any cause.
Time frame: Up to 5 years and 11 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Galinpepimut-S | Progression-free Survival | 10.1 months |
| Control | Progression-free Survival | 7.4 months |
Secondary
Immune Response
Immunogenicity of galinpepimut-S and control from a subset of participants
Time frame: 12 weeks
Population: Data were available from 22 participants only
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Galinpepimut-S | Immune Response | CD4 Elispot | Negative | 4 Participants |
| Galinpepimut-S | Immune Response | CD8 Elispot | Not tested | 8 Participants |
| Galinpepimut-S | Immune Response | CD8 Elispot | Positive | 1 Participants |
| Galinpepimut-S | Immune Response | Tetramer assay positive | Positive | 1 Participants |
| Galinpepimut-S | Immune Response | CD4 Elispot | Not tested | 2 Participants |
| Galinpepimut-S | Immune Response | Tetramer assay positive | Negative | 0 Participants |
| Galinpepimut-S | Immune Response | CD8 Elispot | Negative | 1 Participants |
| Galinpepimut-S | Immune Response | Tetramer assay positive | Not tested | 9 Participants |
| Galinpepimut-S | Immune Response | CD4 Elispot | Positive | 4 Participants |
| Control | Immune Response | Tetramer assay positive | Not tested | 7 Participants |
| Control | Immune Response | CD4 Elispot | Positive | 1 Participants |
| Control | Immune Response | CD4 Elispot | Negative | 8 Participants |
| Control | Immune Response | CD4 Elispot | Not tested | 3 Participants |
| Control | Immune Response | CD8 Elispot | Positive | 1 Participants |
| Control | Immune Response | CD8 Elispot | Negative | 3 Participants |
| Control | Immune Response | CD8 Elispot | Not tested | 8 Participants |
| Control | Immune Response | Tetramer assay positive | Positive | 2 Participants |
| Control | Immune Response | Tetramer assay positive | Negative | 3 Participants |
Secondary
Overall Survival
Median overall survival (OS) is estimated from time of randomization to all cause mortality
Time frame: Uo to 5 years and 11 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Galinpepimut-S | Overall Survival | 22.8 months |
| Control | Overall Survival | 18.3 months |