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

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

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.

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.

• 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.