Depleted Immune Suppressor Stem Cell Transplant in Enhancing Immune Response to Vaccines in Patients with Multiple Myeloma
- Diagnosis of multiple myeloma as per updated International Myeloma Working Group (IMWG) criteria
- Must have measurable disease defined as: for secretory MM, serum monoclonal protein >= 1.0 g/dL, urine monoclonal protein >= 200 mg/24 hrs, and involved free light chain >= 10 mg/dL; or in case of non-secretory MM, bone marrow plasma cell percentage >= 30%
- Must have standard risk myeloma
- Must have received bortezomib, lenalidomide and dexamethasone (VRd) as a form of induction therapy pre-autologous hematopoietic stem cell transplantation (AHSCT) (use of cyclophosphamide, bortezomib and dexamethasone may be allowed for up to 2 weekly doses before initiation of VRd induction, if necessary clinically for cytoreduction)
- Able to understand and sign a consent form
- Creatinine clearance equal or > 60 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
- Total bilirubin =< 2.5 times the upper limit of the institutional normal values
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times the upper limit of the institutional normal values
- 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 6 months of pre-transplant MM chemotherapy is allowed (from the date of the start of the induction therapy)
- Karnofsky performance status (KPS) >= 70% or Eastern Cooperative Oncology Group (ECOG) 0-2
- 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 Revlimid pre-transplant as a way of ensuring safe transplant planning
- Participation in another clinical study with an investigational product during the last 28 days
- Prior stem cell transplant (either autologous or allogeneic)
- Creatinine clearance < 60 ml/min (calculated)
- High risk MM defined as those with the following disease, fluorescence in situ hybridization and/or cytogenetic features: del17p, del1p with 1q gain, t(4;14), t(14;16), t(14;20), > 1 cytogenetic abnormality on karyotype, hypodiploid, plasma cell leukemia (primary or secondary), or subjects who failed to achieve >= partial response (PR) to induction therapy (i.e. VRd) and required salvage induction prior to AHSCT
- Documented central nervous system or extramedullary disease
- Significant organ dysfunction deemed to carry inappropriate risk for AHSCT
- Intention or plans for cyclophosphamide mobilization
- Known allergic reactions after previous tetanus diphtheria vaccination or had a condition of Guillain Barre syndrome (GBS)
- Known active hepatitis B, C or human immunodeficiency virus (HIV) infections on initial assessment
- Enrollment on any other transplant related protocols
I. To compare the cellular and humoral vaccine response post-transplant between the two arms by performing enzyme-linked immunosorbent assay (Elisa), and T-cell enzyme-linked immunospot (ELISPOT) assays.
II. To determine the feasibility and safety of this approach.
I. To compare post-transplant recovery of innate and adaptive immune cells (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. To compare progression free survival (PFS) at 2 years post-transplant.
I. To compare the depth of multiple myeloma (MM) response by international myeloma working group (IMWG) criteria, including analyzing minimal residual disease (MRD) status at 3 months post-transplant for those patients in stringent complete response (sCR) between the two arms.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive 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.
Trial Phase Phase II
Trial Type Treatment
University of Nebraska Medical Center
- Primary ID 669-19
- Secondary IDs NCI-2015-00743, IRB00079982
- Clinicaltrials.gov ID NCT02700841