Phase 1/2a Study of Cancer Vaccine to Treat Smoldering Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and tolerability of PVX-410, (a cancer vaccine), treatment regimen for patients with smoldering multiple myeloma as a single agent and in combination with lenalidomide.

Detailed Description
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This is a dose escalation, phase 1/2a study to assess the safety and tolerability of PVX-410, (a multi-peptide cancer vaccine), treatment regimen in patients with smoldering multiple myeloma as a single agent and in combination with lenalidomide.. Approximately 22 patients will receive six (6) bi-weekly, subcutaneous injections of PVX-410 for a total of twelve (12) weeks of treatment. Safety will be monitored throughout the study. Tolerability, immunogenicity and clinical response will also be measured as described in the protocol.

Official Title
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A Phase 1/2a Dose Escalation Study of PVX-410, a Multi-Peptide Cancer Vaccine, in Patients With Smoldering Multiple Myeloma

Conditions
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Smoldering Multiple Myeloma

Intervention / Treatment
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* Biological: PVX-410


Participation Criteria
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Eligibility Criteria
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Patient has confirmed clinical diagnosis of SMM according to a definition derived from the International Myeloma Working Group (IMWG) definition: serum M-protein ≥3 g/dL or bone marrow clonal plasma cells (BMPC) greater than or equal to 10%, or both, along with normal organ and marrow function (CRAB) within 4 weeks before baseline. C: Absence of hypercalcemia, evidenced by a calcium <10.5 mg/dL. R: Absence of renal failure, evidenced by a creatinine <2.0 mg/dL or calculated creatinine clearance (using the Modification of Diet in Renal Disease [MDRD] formula) >50 mL/min. A: Absence of anemia, evidenced by a hemoglobin >10 g/dL. B: Absence of lytic bone lesions on standard skeletal survey. Patient is at higher than average risk of progression to active MM, defined as having 2 or more of the following features: Serum monoclonal (M)-protein ≥3 g/dL. BMPC greater than or equal to 10%. Abnormal serum free light chain (FLC) ratio (0.26-1.65). Patient has a life expectancy of greater than 6 months Patient is human leukocyte antigen (HLA)-A2 positive. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patient has adequate bone marrow function, evidenced by a platelet count ≥75×109/L and an absolute neutrophil count (ANC) ≥1.0×109/L within 2 weeks before baseline. Patient has adequate hepatic function, evidenced by a bilirubin ≤2.0 mg/dL and an alanine transaminase (ALT), and aspartate transaminase (AST) ≤2.5× the upper limit of normal (ULN) within 2 weeks before baseline. If of child-bearing potential, patient agrees to use adequate birth control measures during study participation. If a female of child-bearing potential, patient has negative urine pregnancy test results within 2 weeks before baseline and is not lactating. Patient (or his or her legally accepted representative) has provided written informed consent to participate in the study. Exclusion Criteria: Patient has symptomatic multiple myeloma, as defined by any of the following: Lytic lesions or pathologic fractures. Anemia (hemoglobin <10 g/dL). Hypercalcemia (corrected serum calcium >11.5 mg/dL). Renal insufficiency (creatinine >2 mg/dL). Other: symptomatic hyperviscosity, amyloidosis. Patient has abnormal cardiac status, evidenced by any of the following: New York Heart Association (NYHA) stage III or IV congestive heart failure (CHF). Myocardial infarction within the previous 6 months. Symptomatic cardiac arrhythmia requiring treatment or persisting despite treatment. Patient is receiving any other investigational agent. Patient has a current active infectious disease or positive serology for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV). Patient has a history of or current auto-immune disease. Patient has been vaccinated with live attenuated vaccines within 4 weeks before study vaccination.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 95 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PVX-410, .4 mg dose<br>Approximately 3 patients will receive 6, bi-weekly, subcutaneous injections of a .4 mg dose of PVX-410 in combination with an intramuscular injection of Hiltonol (poly ICLC). Patients will complete a 12 week treatment phase and then will be followed for safety, immunogenicity and clinical response for 12 months. | Biological: PVX-410<br>* Approximately 10 patients will receive 6, bi-weekly, subcutaneous injections of a dose of PVX-410 in combination with an intramuscular injection of Hiltonol (Poly ICLC). Patients will complete a 12 week treatment phase and then will be followed for safety, immunogenicity and clinical response for 12 months<br>* Other names: Revlimid;|
| Experimental: PVX-410, .8 mg dose<br>Approximately 10 patients will receive 6, bi-weekly, subcutaneous injections of an .8 mg dose of PVX-410 in combination with an intramuscular injection of Hiltonol (Poly ICLC). Patients will complete a 12 week treatment phase and then will be followed for safety, immunogenicity and clinical response for 12 months. | Biological: PVX-410<br>* Approximately 10 patients will receive 6, bi-weekly, subcutaneous injections of a dose of PVX-410 in combination with an intramuscular injection of Hiltonol (Poly ICLC). Patients will complete a 12 week treatment phase and then will be followed for safety, immunogenicity and clinical response for 12 months<br>* Other names: Revlimid;|
| Experimental: PVX-410 plus lenalidomide<br>Approximately 10 patients will receive 6, bi-weekly, subcutaneous injections of an .8 mg dose of PVX-410 in combination with an intramuscular injection of Hiltonol (Poly ICLC). Patients will also receive 3 cycles of lenalidomide. Patients will complete a 12 week treatment phase and then will be followed for safety, immunogenicity and clinical response for 12 months | Biological: PVX-410<br>* Approximately 10 patients will receive 6, bi-weekly, subcutaneous injections of a dose of PVX-410 in combination with an intramuscular injection of Hiltonol (Poly ICLC). Patients will complete a 12 week treatment phase and then will be followed for safety, immunogenicity and clinical response for 12 months<br>* Other names: Revlimid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All adverse events will be recorded. |  | Throughout treatment phase (3 months) and follow up period (12 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune response to the vaccine will be measured | Patient blood samples will be measured for immune response through ELISPOT and Pentamer assays. | Designated timepoints during the treatment phase (3 months) and follow up phase (12 months) |