This research study is a Phase I clinical trial, which tests the safety of an investigational
intervention and also tries to define the appropriate dose of the investigational
intervention to use for further studies. "Investigational" means that the intervention is
being studied.
In this research study, the investigators are studying Smoldering Multiple Myeloma.
Smoldering Multiple Myeloma is an early precursor to a rare blood cancer known as Multiple
Myeloma, which affects plasma cells. The study will test two different combinations of the
study drugs; a combination of the vaccine (PVX-410) along with Citarinostat (CC-96241) and
triple combination of the vaccine, Citarinostat, and Lenalidomide.
The vaccine (PVX-410) is a multi-peptide vaccine that contains four synthetic peptides that
together are intended to induce a T cell-mediated immune response against the myeloma. The
FDA (the U.S. Food and Drug Administration) has not approved PVX-410 as a treatment for any
disease.
Citarinostat is an orally active, small-molecule Histone Deacetylase (HDAC) Inhibitor which
is being combined here to further augment the immune activity of the vaccine. Citarinostat
has not been approved by the FDA as a treatment for any disease.
Lenalidomide is commercially available analogue of thalidomide with immunomodulatory,
antiangiogenic, and antineoplastic properties that has demonstrated an increase in immune
activity in previous trials. The FDA has approved Lenalidomide as a treatment option for
Smoldering Multiple Myeloma. Lenalidomide is being added to the combination of the vaccine
and Citarinostat because it is hypothesized that co-administration of lenalidomide along with
Citarinostat would further enhance the T cell-mediated immune response induced by PVX-410.
Inclusion Criteria:
- 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.
