Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia
Conditions
Keywords
Galinpepimut-S, WT1 analog peptide vaccine, 10-143, Wilms Tumor-1 protein, SLS-001, complete remission, overall survival
Brief summary
This trial will assess the safety and efficacy of vaccination with galinpepimut-S (GPS), a WT1 peptide vaccine, in patients who are in complete remission from leukemia. Participants will receive vaccinations with GPS every 2 weeks for 10 weeks (a total of 6 vaccinations). In the absence of disease recurrence at Week 12 and if clinically stable after the first 6 vaccinations, participants may continue to receive up to six more vaccinations every month.
Detailed description
This clinical study is conducted in patients in complete remission from acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). The primary objective is to assess the effect of vaccination with galinpepimut-S (GPS) on patient survival and the safety profile. 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 will receive vaccinations with GPS every 2 weeks for 10 weeks (a total of 6 vaccinations). In the absence of disease recurrence at Week 12 evaluation and if clinically stable after the first 6 vaccinations, participants may continue to receive up to six more vaccinations every month. Following the last vaccination, participants will be followed regularly (every 1 to 3 months) in an outpatinet setting for up to 3 years from the first treatment date.
Interventions
BIOLOGICALGalinpepimut-S
Galinpepimut-S admixed with the adjuvant Montanide following specified schedule
BIOLOGICALGM-CSF
subcutaneous injection
OTHERMontanide
adjuvant
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
* Morphologic confirmation of a diagnosis of AML or ALL at MSKCC * Patients will have completed induction therapy, achieved 1st CR and will have completed any planned postremission therapy. Patients are not candidates for allogeneic stem cell transplantation. For purposes of this study, patients who are not candidates for allogeneic stem cell transplantation shall be defined as 1) those who do not meet the eligibility criteria of an open allogeneic transplant protocol or 2) those who do not have a suitable available HLA matched donor available or 3) those who refuse to undergo stem cell transplantation or 4) those patients whose disease is characterized by good risk features (For AML the following cytogenetic subtypes: t(8;21), inv (16), or t(16;16), t(15;17), normal karyotype with mutated NPM1 and negative for tandem duplication of FLT-3. For ALL: T cell phenotype of any B lineage disease exclusive of t(9;22) or t(4;11) in whom allogenic stem cell transplantation in 1st CR would not be offered as standard of care. * Alternatively, those patients greater than or equal to 60 years of age who have achieved 1st CR and in whom no further postremission chemotherapy is planned may be enrolled * Patients must have documented WT1 + disease. For purpose of this study, this is defined as detectable presence of any WT1 transcript via RT-PCR on a bone marrow performed at MSKCC within 4 weeks prior to the administration of the first dose of vaccine. * Patients must be within 2 years of achieving CR following chemotherapy * At least 4 weeks must have elapsed between the patient's last chemotherapy or radiation treatment and the first vaccination. * Age ≥ 18 years * Karnofsky performance status ≥ 50% * Hematologic parameters: Absolute neutrophil count (ANC) ≥ 1000/μL * Platelets \> 50 k/μL Biochemical parameters: * Total bilirubin ≤ 2.0 mg/dL AST and ALT ≤ 2.5 x upper limits of normal * Creatinine ≤ 2.0 mg/dL
Exclusion criteria
* Pregnant or lactating women * Patients with documented evidence of leptomeningeal disease * Patients who have undergone autologous or allogeneic stem cell transplantation * Patients with active infection requiring systemic antimicrobials * Patients taking systemic corticosteroids * Patients with serious unstable medical illness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 3 years | OS at 3 years, measured from first treatment with GPS to patient's survival status at 3 years or more |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | 5 years and 8 months | Time to PFS measured from first administration of GPS to relapse or death from any cause |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Galinpepimut-S + Montanide + GM-CSF Galinpepimut-S (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 with no recurrence after Week 12 and who are clinically stable may be eligible to receive up to 6 additional monthly vaccinations. | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | Galinpepimut-S + Montanide + GM-CSF |
|---|---|
| Age, Continuous | 64 years |
| HLA-A* 02:01 positive | 9 Participants |
| Karnofsky performance status | 93.8 scores on a scale STANDARD_DEVIATION 5.9 |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 10 / 22 |
| other Total, other adverse events | 21 / 22 |
| serious Total, serious adverse events | 1 / 22 |
Outcome results
Primary
Overall Survival
OS at 3 years, measured from first treatment with GPS to patient's survival status at 3 years or more
Time frame: 3 years
Population: Of the 22 patients, 19 (86.4%) were evaluable for survival at 3 years,
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Galinpepimut-S + Montanide + GM-CSF | Overall Survival | 47 percentage of participants |
Secondary
Progression-free Survival
Time to PFS measured from first administration of GPS to relapse or death from any cause
Time frame: 5 years and 8 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Galinpepimut-S + Montanide + GM-CSF | Progression-free Survival | 283 days |