Clinical Trials /

Enhancing Anti-Myeloma Vaccine Response After Autologous Stem Cell Transplantation

NCT02700841

Description:

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.

Related Conditions:
  • Multiple Myeloma
  • Plasma Cell Leukemia
Recruiting Status:

Suspended

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Enhancing Anti-Myeloma Vaccine Response After Autologous Stem Cell Transplantation
  • Official Title: Enhancing Anti-Myeloma Vaccine Response After Autologous Stem Cell Transplantation

Clinical Trial IDs

  • ORG STUDY ID: IRB00079982
  • SECONDARY ID: NCI-2015-00743
  • SECONDARY ID: WINSHIP2905-15
  • NCT ID: NCT02700841

Conditions

  • Plasma Cell Myeloma

Interventions

DrugSynonymsArms
MelphalanAlkeran, L-PAM, L-Phenylalanine Mustard, Phenylalanine Mustard, SarcolysinArm I (vaccines, CD34 transplant, DLI)
T Cell-Depleted Hematopoietic Stem Cell TransplantationArm I (vaccines, CD34 transplant, DLI)
Tetanus Toxoid VaccineTetanus Toxoid, TTArm I (vaccines, CD34 transplant, DLI)
Therapeutic Autologous LymphocytesAutologous T-cellsArm I (vaccines, CD34 transplant, DLI)
Trivalent Influenza VaccineFlu prophylaxis, Flu shot, Flu vaccination, Fluzone, Influenza VaccineArm I (vaccines, CD34 transplant, DLI)
XBP1-US/XBP1-SP/CD138/CS1 Multipeptide Vaccine PVX-410PVX-410Arm I (vaccines, CD34 transplant, DLI)

Purpose

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.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (vaccines, CD34 transplant, DLI)ExperimentalARM I: Patients receive XBP1-US/XBP1-SP/CD138/CS1 multipeptide vaccine PVX-410 SC every 2 weeks for 3 doses before transplant and on days 1, 15, and 30 and tetanus and influenza vaccines IM with the 3rd dose vaccine dose before transplant. Patients receive conditioning regimen comprising high-dose melphalan IV on day -2 and undergo autologous CD34 HSCT on day 0. Patients also receive autologous DLI IV on day 2.
  • Melphalan
  • T Cell-Depleted Hematopoietic Stem Cell Transplantation
  • Tetanus Toxoid Vaccine
  • Therapeutic Autologous Lymphocytes
  • Trivalent Influenza Vaccine
  • XBP1-US/XBP1-SP/CD138/CS1 Multipeptide Vaccine PVX-410
Arm II (vaccines, stem cell transplant)Active ComparatorPatients 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 AHSCT on day 0.
  • Melphalan
  • Tetanus Toxoid Vaccine
  • Trivalent Influenza Vaccine
  • XBP1-US/XBP1-SP/CD138/CS1 Multipeptide Vaccine PVX-410

Eligibility Criteria

        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.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in influenza antibody titer as measured by hemagglutination inhibition assay (HAI)
Time Frame:Baseline to 30, 70, 90, and 180 days post-transplant
Safety Issue:
Description:First, paired t-test will be employed to test the change in influenza antibody titer at days 30, 70, 90, and 180 post-transplant from the baseline among each group, respectively. Second, two sample t-test will be further used to compare the change of influenza antibody between the two groups at days 30, 70 & 90, and 180 post-transplant, respectively. Mixed model will be finally employed to compare the change pattern of influenza antibody between the two groups over the whole post-transplant follow up periods, including measurements at baseline and days 30, 70 & 90 post-transplant

Secondary Outcome Measures

Measure:Change in absolute lymphocyte count (ALC)
Time Frame:Baseline to 15 and 30 days post-transplant
Safety Issue:
Description:The paired t-test will be employed to test the changes in ALC at days 15 and 30 post AHSCT from the baseline among each group, respectively. The two sample t-test will be further used to compare the change of ALC between the two groups at days 15 and 30 post-AHSCT. Mixed model will be finally employed to compare the change pattern of ALC between the two groups over the whole follow up periods. The two sample t-test will also be used to compare the change of ALC between the relapsed patients and patients without relapse, respectively.
Measure:Change in immune cells (T cells cluster of differentiation 8 [CD8], CD4)
Time Frame:Baseline to 15 and 30 days post-transplant
Safety Issue:
Description:The paired t-test will be employed to test the change in immune cells (T cells CD8, CD4). The two sample t-test will be further used to compare the change of change in immune cells between the two groups at days 15 and 30 post-AHSCT. The two sample t-test will also be used to compare the change of immune cells between the relapsed patients and patients without relapse, respectively.
Measure:Change in NK cells
Time Frame:Baseline to up to day 30
Safety Issue:
Description:The paired t-test will be employed to test the change in NK cells.
Measure:Change in XBP1-US/XBP1-SP/CD138/CS1 multipeptide vaccine PVX-410 (PVX-410) tetramer+/interferon (IFN) gamma+ cell levels
Time Frame:Baseline to 30, 70, 90, and 180 days post-transplant
Safety Issue:
Description:Paired t-test will be employed to test the change in PVX-410) tetramer+/IFN+ cells at days 30, 70, 90, & 180 post-transplant from baseline among each group. Two sample t-test will be further used to compare the change in PVX-410 tetramer+ cells at days 30, 70, 90, and 180 post-transplant, respectively. Mixed model will be employed to compare the change pattern of PVX-410 tetramer+/IFN+ cells between the two groups over the whole post-transplant follow up periods, including measurements at baseline and days 30, 70, 90, and 180 post-transplant.
Measure:Changes in absolute monocyte counts (AMC)
Time Frame:Baseline to 15 and 30 days post-transplant
Safety Issue:
Description:The paired t-test will be employed to test the changes in AMC at days 15 and 30 post AHSCT from the baseline among each group, respectively. The two sample t-test will be further used to compare the change of AMC between the two groups at days 15 and 30 post-AHSCT. Mixed model will be finally employed to compare the change pattern of AMC between the two groups over the whole follow up periods. The two sample t-test will also be used to compare the change of AMC between the relapsed patients and patients without relapse, respectively.
Measure:Engraftment time
Time Frame:Up to 180 days post-transplant
Safety Issue:
Description:Engraftment will be treated as binary variable. Chi-square test will be used to compare the binary status of engraftment variables between the two groups, respectively.
Measure:Functional benefit of depleting immune suppressive cells from granulocyte-colony stimulating factor (G-CSF) (filgrastim) mobilized autologous peripheral blood stem grafts
Time Frame:Baseline to 30, 70, 90, and 180 days post-transplant
Safety Issue:
Description:Paired t-test will be employed to test the change in PVX-410) tetramer+/IFN+ cells at days 30, 70, 90, & 180 post-transplant from baseline among each group. Two sample t-test will be further used to compare the change in PVX-410 tetramer+ cells at days 30, 70, 90, and 180 post-transplant, respectively. Mixed model will be employed to compare the change pattern of PVX-410 tetramer+/IFN+ cells between the two groups over the whole post-transplant follow up periods, including measurements at baseline and days 30, 70, 90, and 180 post-transplant.
Measure:Incidence of auto immune side effects using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.02
Time Frame:Up to 180 days post-transplant
Safety Issue:
Description:The development of any auto immune side effects will be treated as binary variable. Chi-square test will be used to compare the binary status of any auto immune side effect variables between the two groups.
Measure:Incidence of infections
Time Frame:Up to 180 days post-transplant
Safety Issue:
Description:Infections will be treated as binary variable. Chi-square test will be used to compare the binary status of infection variables between the two groups, respectively.
Measure:Progression-free survival
Time Frame:Up to 2 years post-transplant
Safety Issue:
Description:Kaplan Meier method, Logrank test, and Cox model will be employed to investigate the effect of ALC, AMC, and immune cells on survival post AHSCT.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Suspended
Lead Sponsor:Emory University

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