Dendritic Cell DKK1 Vaccine for Monoclonal Gammopathy and Stable or Smoldering Myeloma

The overall objective of this pilot study is to determine the safety and preliminary efficacy
of a dendritic cell DKK1 vaccine in view of possible future use as a strategy to prevent
progression of asymptomatic plasma cell disorders, maintain disease control, and ultimately
contribute to eradication of multiple myeloma, light and heavy chain amyloidosis,
immunoglobulin deposition disease, and other malignant and non-malignant diseases related to
transformed plasma cells.

Primary Objective Confirm the safety of dendritic cell DKK1 vaccine given every two weeks for
three doses in patients with monoclonal gammopathy, stable or smoldering myeloma.

Secondary Objectives

1. Assess response according to international response criteria (> partial response, PR)
and clinical benefit response (>minor response, MR, according to adapted EBMT criteria)

2. Determine time to progression

3. Describe progression-free and overall survival

Correlative Objectives

1. Explore correlation between myeloma DKK1 and PDL-1 expression and response

2. Determine cellular immune response

3. Assess serologic anti-DKK1 antibody response

Study design including dose escalation / cohorts Pilot study with 3 patient safety run-in,
possible dose level -1 (DL-1) if dose limiting toxicity occurs in one or more patients at the
target dose level, and, at the first dose level where no dose limiting toxicity occurs,
extension by 12 patients.

DLT will be defined as any vaccine related toxicity > grade 3 that does not resolve to grade
< 2 within 7 days. If any DLT occurs at DL-1 enrollment will be stopped and an amendment will
be discussed.

Inclusion Criteria:

- At any time prior to enrollment subjects must have IgG, IgA, kappa, or lambda
monoclonal gammopathy confirmed in at least two assessments at least three months
apart or histologically confirmed multiple myeloma or carry a diagnosis of smoldering
myeloma based on prior documentation of serum m-spike (IgG or IgA) of at least 3g/dL
serum m-spike (IgG or IgA) or 24h urine m-spike of at least 500mg/24h.

- Within 28 days prior to enrollment persistence of the clonal plasma cell disorder must
be documented by presence of a clonal band on immunofixation of blood or urine or an
abnormal serum free kappa/lambda ratio.

- Subjects with myeloma related organ dysfunction must have received prior therapy,
reached at least partial remission with at least one of any number of prior regimens,
and be candidates for observation off myeloma therapy based on lack of progression at
least stable disease for at least 90 days prior to at study entry.

- Performance status ECOG performance status ≤ 2.

- Subjects must have laboratory test results within the following ranges:

- Hemoglobin ≥ 9.0 g/dl

- Absolute neutrophil count ≥ 1,500/mcL

- Platelet count ≥ 100,000/mcL

- Total bilirubin < 2.5 x institutional upper limit of normal

- AST (SGOT) ≤ 2.5 X institutional upper limit of normal

- ALT (SGPT) ≤ 2.5 X institutional upper limit of normal

- Calculated creatinine clearance (Cockcroft-Gault) ≥ 30ml/min

- Anti-myeloma treatment with proteasome inhibitors, IMiDsTM, corticosteroids, low dose
cyclophosphamide (≤ 50mg per day) must have been discontinued at least 14 days prior
to study entry. Conventional chemotherapy at conventional doses including
cyclophosphamide at > 50mg per day must have been discontinued at least 28 days prior
to study entry. At least 180 days must have passed since high dose chemotherapy used
in the context of autologous stem cell transplantation. Prior radiation must have been
completed at least 14 days prior to enrollment.

- Subjects must have the ability to understand and the willingness to sign a written
informed consent document.

Exclusion Criteria:

- Subjects receiving any other investigational agents.

- Concurrent use of any plasma cell directed therapy including corticosteroids (use of
bisphosphonates is allowed).

- Subjects who have previously received an allogeneic stem cell transplant.

- Subjects with uncontrolled intercurrent illness including, but not limited to ongoing
or active infection (including active HIV or hepatitis), symptomatic congestive heart
failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social
situations that would limit compliance with study requirements.

- Women with childbearing potential (last menstrual period within less than 24 months
unless hysterectomy or bilateral oophorectomy has been performed since) as well as
pregnant women are excluded from this study because DKK1 is expressed in placental
tissue and a DKK1 immune response could harm the child. Breastfeeding women are
excluded from this study because antibodies made in response to the dendritic cell
DKK1 vaccine could enter milk and affect the health of the breastfed child.