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Depleted Immune Suppressor Stem Cell Transplant in Enhancing Immune Response to Vaccines in Patients with Multiple Myeloma

Trial Status: Temporarily Closed to Accrual and Intervention

This pilot, randomized phase II trial studies how well depleted immune suppressor stem cell transplant works compared to standard stem cell transplant in enhancing immune response to vaccines in patients with multiple myeloma (MM). Chemotherapy and the patient's own stem cells are effective in treating MM, however there is a risk of disease returning due to poor recovery of the immune system as shown to poor response to vaccines to prevent infections. Before chemotherapy, patients' stem cells are collected and certain immune cells called suppressor cells are removed from the stem cells. Patients then receive chemotherapy to kill cancer cells and after that the immune depleted stem cells are returned to them to replace the blood-forming cells that were destroyed by chemotherapy. Giving depleted immune suppressor stem cells transplant to patients with MM may result in a more robust immune response to vaccines after transplant and may prevent MM from returning. It is not yet known whether depleted immune suppressor stem cell transplant is more effective than standard stem cell transplant in enhancing immune response to vaccines in patients with multiple myeloma.

Inclusion Criteria

  • 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

Exclusion Criteria

  • 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

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: COMPLETED
Contact: Zaid S. Al-Kadhimi
Phone: 404-778-1900

Nebraska

Omaha
University of Nebraska Medical Center
Status: APPROVED
Contact: Muhamed Baljevic

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

EXPLORATORY OBJECTIVE

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

Lead Organization
University of Nebraska Medical Center

Principal Investigator
Muhamed Baljevic

  • Primary ID 669-19
  • Secondary IDs NCI-2015-00743, IRB00079982
  • Clinicaltrials.gov ID NCT02700841