A Study of PVX-410, a Cancer Vaccine, and Citarinostat +/- Lenalidomide for Smoldering MM

• Patient has confirmed SMM according to a definition derived from the International Myeloma Working Group (IMWG) definition (International Working Group, 2003): serum M-protein ≥3 g/dL or BMPC >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 \< 1.5 mg/dL (177 µmol/L) 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 M-protein ≥3 g/dL.
  • BMPC >10%.
  • Abnormal serum FLC ratio (0.26-1.65).
• Patient is aged 18 years or older.
• Patient has a life expectancy of greater than 6 months.
• Patient is HLA-A2+
• 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×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 serum pregnancy test results within 2 weeks before baseline and is not lactating.
• If assigned to receive lenalidomide and a female of reproductive potential, must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program.
• If assigned to receive lenalidomide, patient must be registered into the mandatory Revlimid REMS® program and be willing and able to comply with the requirements of the REMS® program.
• Patient (or his or her legally accepted representative) has provided written informed consent to participate in the study.
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Exclusion Criteria:

• Patient has symptomatic MM, 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 > 1.5 mg/dL).
  • Other: symptomatic hyperviscosity, amyloidosis.
• Patient has a history of a prior malignancy within the past 3 years (excluding resected basal cell carcinoma of the skin or in situ cervical cancer).

• 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), hepatitis B virus (HBV), or hepatitis A virus (HAV).
• Patient has a history of or current auto-immune disease.
• Patient has been vaccinated with live attenuated vaccines within 4 weeks before study vaccination.
• Any previous treatment with a HDAC inhibitor, including Citarinostat.
• Had involvement in the planning and/or conduct of the study by association with the Sponsor, study drug supplier(s) or study center or was previously enrolled in the present study.
• Current or prior use of immunosuppressive medication within 28 days before the first dose of treatment, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
• Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, active peptic ulcer disease or gastritis, active bleeding diatheses, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent
• Known history of previous clinical diagnosis of tuberculosis.