Enhancing Anti-Myeloma Vaccine Response After Autologous Stem Cell Transplantation

PRIMARY OBJECTIVES:

I. To compare the cellular and humoral vaccine response post-transplant between the two arms.

II. To determine the feasibility and safety of this approach.

SECONDARY OBJECTIVES:

I. To compare post-transplant recovery of innate and adaptive immune cells (cluster of
differentiation [CD] CD8, CD4, CD19, natural killer cells [NK], gamma delta T-cells), in
addition to T-cell phenotype markers between the two arms.

II. To compare post-transplant recovery of regulatory T-cells (T-regs) and myeloid derived
suppressor cells (MDSCs) between the two arms.

III. Progression free survival at 2 years post-transplant. IV. To compare multiple myeloma
(MM) minimal residual disease (MRD) status at 3 months post-transplant between the two arms.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive X box binding protein-1(XBP1)-US/XBP1-SP/CD138/CS1 multipeptide
vaccine PVX-410 subcutaneously (SC) every 2 weeks for 3 doses before transplant and on days
1, 15, and 30 and tetanus and influenza vaccines intramuscularly (IM) with the 3rd dose
vaccine dose before transplant. Patients receive conditioning regimen comprising high-dose
melphalan intravenously (IV) on day -2 and undergo autologous CD34 hematopoietic stem cell
transplant (HSCT) on day 0. Patients also receive autologous donor lymphocyte (DLI) IV on day
2.

ARM II: Patients receive XBP1-US/XBP1-SP/CD138/CS1 multipeptide vaccine PVX-410
subcutaneously and tetanus and influenza vaccines as in Arm I. Patients receive high-dose
melphalan IV on day -2 and undergo autologous hematopoietic stem cell transplant (AHSCT) on
day 0.

Inclusion Criteria:

- Diagnosis of multiple myeloma

- The first 3 patients on the experimental arm will be high risk myeloma and subsequent
patients will be low risk myeloma. High risk multiple myeloma patients:

- Have deletion (del) 17p, del 1p, T (4;14), T (14;16)

- Have plasma cell leukemia (PCL)

- Have > 1 cytogenetic abnormality

- Are hypodiploid

- Have failed adequate initial therapy (lenalidomide, bortezomib, dexamethasone
[RVD], thalidomide, bortezomib, and dexamethasone [TVD], or cyclophosphamide,
bortezomib, and dexamethasone [CyBorD])

- Have planned to receive non-chemotherapy/cytotoxic salvage regimens (except for
single agent cyclophosphamide).

- Able to understand and sign a consent form

- Creatinine clearance equal or > 50 ml/min (calculated)

- Ejection fraction equal or > 50% before admission for transplant as per institutional
standards. Patients with coronary heart disease (recent myocardial infarctions,
angina, cardiac stent, or bypass surgery in the last 6 months or arrhythmia) need to
be cleared by cardiology as per Emory bone marrow transplant (BMT) standards.

- Serum bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) less
than 3 X upper limit of normal

- Forced vital capacity (FVC), forced expiratory volume in one second (FEV1) or
diffusion capacity of carbon monoxide (DLCO) > 50% predicted before admission for
transplant as per institutional standards. Patients on home oxygen are not allowed on
the protocol.

- No more than six months' worth of multiple myeloma chemotherapy is allowed (from the
date of the start of the induction therapy)

- Karnofsky performance status (KPS) ≥ 70%

- Patients must be eligible to receive melphalan dose of 200 mg/m²

- Patients must be human leukocyte antigen (HLA) A2 positive by polymerase chain
reaction (PCR) typing

- A female of child-bearing potential, must have two negative urine pregnancy test
results within 10 to 14 days prior to starting the first dose of vaccine and
lenalidomide pre-transplant

Exclusion Criteria:

- Patient with a prior stem cell transplant (both autologous and allogeneic)

- Creatinine clearance < 50 ml/min (calculated)

- Patients with documented central nervous system (CNS) disease

- Significant organ dysfunction deemed to be inappropriate for autologous
transplantation

- Intention or plans for cyclophosphamide mobilization

- Patients with active hepatitis B, C or human immunodeficiency virus (HIV) infections
(PCR positive)

- Enrollment on any other transplant related protocols

- Pregnant women are excluded from participating in this study; collect urine for
pregnancy test for female patients who are not postmenopausal or surgically sterile
which is part of standard of care. If positive, repeat and confirm results prior to
visit 2; a second positive test will result in exclusion of the patient from the
study.