Multiple Myeloma
Conditions
Keywords
WT1 Analog Peptide Vaccine, 12-288, Galinpepimut-S, GPS, Maintenance therapy, Autologous Stem Cell Transplant (ASCT), Wilms Tumor 1, Immunotherapeutic Agent, Post-ASCT maintenance, SLS-001
Brief summary
The purpose of this trial is to assess the immune response after vaccination with a peptide vaccine called galinpepimut-S (or GPS) in a type of blood cancer called multiple myeloma. A protein called WT1 is often present in cancerous cells and GPS can train the immune system to recognize and kill the cancerous cells containing WT1. This study will also assess the safety of GPS, effect on disease, and on survival. Participants who has undergone autologous stem cell transplant (ASCT) will receive vaccinations with GPS every 2 weeks for 10 weeks (a total of 6 vaccinations). Vaccinations will start 12 to 22 days after ASCT. In the absence of disease progression and if clinically stable after the first 6 vaccinations, participants may continue to receive six more vaccinations every month. The use of post-ASCT maintenance therapy is allowed starting from 3 months after transplant.
Detailed description
This is an early phase clinical study conducted in patients with newly diagnosed high-risk multiple myeloma to examine the effects of vaccination with galinpepimut-S (GPS) on clinical and immunobiological indices. The study is titled A Pilot Trial of a WT1 Analog Peptide Vaccine (Galinpepimut-S) in Patients With Multiple Myeloma Following Autologous Stem Cell Transplantation and is designed as a single-arm, single-institution, open-label study. The primary objective is to assess immune response 12 to 14 weeks after administration of GPS in patients with new diagnosed multiple myeloma (MM) following autologous stem cell transplant (ASCT). Secondary objective includes assessing the safety profile, progression-free survival, and overall survival. Galinpepimut-S (GPS) consists of four WT1-derived peptides which have been chosen to strengthen antigenicity, but also broaden immunogenicity over a wide range of HLA subtypes, being able to stimulate both CD8+ (MHC Class I)- and CD4+ (MHC Class II)-dependent responses. Galinpepimut-S is administered with the adjuvant Montanide and sargramostim (GM-CSF). Participants who has undergone autologous stem cell transplant (ASCT) will receive vaccinations with GPS every 2 weeks for 10 weeks (a total of 6 vaccinations). Vaccinations will start 12 to 22 days after ASCT. In the absence of disease progression and if clinically stable after the first 6 vaccinations, participants may continue to receive six more vaccinations every month. The use of post-ASCT maintenance therapy with immunomodulatory drugs (IMIDs, eg, thalidomide, lenalidomide) or proteasome inhibitors (PSIs, eg, bortezomib) is allowed from 3 months after transplant.
Interventions
BIOLOGICALGalinpepimut-S
Galinpepimut-S admixed with the adjuvant Montanide following specified schedule
BIOLOGICALGM-CSF
subcutaneous injection
OTHERMontanide
adjuvant
DRUGlenalidomide
optional post-ASCT therapy
DRUGbortezomib
optional post-ASCT therapy
Sponsors
Memorial Sloan Kettering Cancer Center
Sellas Life Sciences Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Symptomatic multiple myeloma, ISS stage 1-3 with confirmed diagnosis of multiple myeloma at MSKCC * Patients must be eligible to undergo autologous stem cell transplantation by standard institutional criteria * Patients must have documented WT1 positive disease. For purpose of this study, this is defined as detectable presence of WT1 expression by immunohistochemistry or by WT1 transcript via RT-PCR on a bone marrow or other plasma cell-related biopsy specimen prior to autologous stem cell transplantation. Bone marrow or other biopsy specimen from time of diagnosis from patients diagnosed at MSKCC or outside hospital may be requested for assessment of WT1 expression by IHC * Age \> or = to 18 years * Karnofsky performance status \> or = to 50% * Hematologic parameters: * Absolute neutrophil count (ANC) \> or = to 1,000/μl * Platelets \> 50,000/μl * Biochemical parameters: * Total bilirubin \< than or = to 2.0 mg/dl * AST and ALT \< than or = to 2.5 x upper limits of normal (ULN) * Creatinine \< than or = to 2.0 mg/dl
Exclusion criteria
* Pregnant or lactating women * Patients with active infection requiring systemic antimicrobials * Patients taking systemic corticosteroids * Patients with serious unstable medical illness * Concurrent malignancies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| WT1 T-cell Immune Response (IR) 12-14 Weeks After First GPS Administration (6 x Administrations) | 12 weeks after the initial GPS vaccine (end of first series [GPS x 6 administrations]) | Number and percentage of participants with CD4 and/or CD8 immune responses against WT1m measured 12-14 weeks after first GPS administration (6 x administrations) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) From Autologous Stem Cell Transplant (ASCT) | 3 years and 8 months | PFS measured from ASCT to time of myeloma progression (as defined by the International Myeloma Working Group \[IMW\] consensus criteria or subject death. |
| Overall Survival (OS) From Autologous Stem Cell Transplant (ASCT) | 3 years and 8 months | OS measured from time of autologous stem cell transplant (ASCT) to the time of subject death |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Galinpepimut-S + Montanide + GM-CSF Galinpepimut-S (GPS) vaccinations are started 12-22 days following autologous stem cell transplantation (ASCT). GPS and Montanide (in a 1 mL emulsion) are administered subcutaneously (s.c.) Q2W on weeks 0, 2, 4, 6, 8, and 10. GM-CSF (70 μg) are administered s.c. one to two days before and on the day of GPS/Montanide administration. Participants whose disease has not progressed and who are clinically stable (no active infection with fevers and no cardiovascular/respiratory compromise) may receive up to 6 additional monthly vaccinations. The use of post-ASCT maintenance therapy is allowed starting 3 months after ASCT.
Galinpepimut-S: Galinpepimut-S admixed with the adjuvant Montanide following specified schedule
GM-CSF: subcutaneous injection
Montanide: adjuvant
lenalidomide: optional post-ASCT therapy
bortezomib: optional post-ASCT therapy | 19 |
| Total | 19 |
Baseline characteristics
| Characteristic | Galinpepimut-S + Montanide + GM-CSF |
|---|---|
| Age, Continuous | 61.3 years |
| Cytogenetics at diagnosis Average risk | 4 Participants |
| Cytogenetics at diagnosis High risk | 15 Participants |
| Post ASCT therapy Lenalidomide alone or in combination | 18 Participants |
| Post ASCT therapy Other (bortezomib) | 1 Participants |
| Prior ASCT 1 | 17 Participants |
| Prior ASCT 2 | 2 Participants |
| Prior therapies | 2 number of therapies |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 8 Participants |
| Type of myeloma IgA | 4 Participants |
| Type of myeloma IgG | 12 Participants |
| Type of myeloma Light chain | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 20 |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
WT1 T-cell Immune Response (IR) 12-14 Weeks After First GPS Administration (6 x Administrations)
Number and percentage of participants with CD4 and/or CD8 immune responses against WT1m measured 12-14 weeks after first GPS administration (6 x administrations)
Time frame: 12 weeks after the initial GPS vaccine (end of first series [GPS x 6 administrations])
Population: Only 15 patients completed 6 x GPS administrations
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Galinpepimut-S + Montanide + GM-CSF | WT1 T-cell Immune Response (IR) 12-14 Weeks After First GPS Administration (6 x Administrations) | 9 Participants |
Secondary
Overall Survival (OS) From Autologous Stem Cell Transplant (ASCT)
OS measured from time of autologous stem cell transplant (ASCT) to the time of subject death
Time frame: 3 years and 8 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Galinpepimut-S + Montanide + GM-CSF | Overall Survival (OS) From Autologous Stem Cell Transplant (ASCT) | NA days |
Secondary
Progression-free Survival (PFS) From Autologous Stem Cell Transplant (ASCT)
PFS measured from ASCT to time of myeloma progression (as defined by the International Myeloma Working Group \[IMW\] consensus criteria or subject death.
Time frame: 3 years and 8 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Galinpepimut-S + Montanide + GM-CSF | Progression-free Survival (PFS) From Autologous Stem Cell Transplant (ASCT) | 717 days |
Post Hoc
WT1 T-cell Immune Response (IR) After Completion of All GPS Administrations
Number and percentage of participants with CD4 and/or CD8 immune responses against WT1 measured after all GPS administrations (12 x administrations)
Time frame: 38 weeks after the initial GPS vaccine (end of booster series [GPS x 12 administrations])
Population: 12 patients completed all 12 x GPS administrations
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Galinpepimut-S + Montanide + GM-CSF | WT1 T-cell Immune Response (IR) After Completion of All GPS Administrations | 12 Participants |