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Enhancing Anti-Myeloma Vaccine Response After Autologous Stem Cell Transplantation

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ClinicalTrials.gov Identifier: NCT02700841
Recruitment Status : Suspended (Protocol is being modified and moved to another institution)
First Posted : March 7, 2016
Last Update Posted : February 21, 2018
Sponsor:
Collaborator:
OncoPep, Inc.
Information provided by (Responsible Party):
Zaid Al-Kadhimi, Emory University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Plasma Cell Myeloma Drug: Melphalan Procedure: Peripheral Blood Stem Cell Transplantation--CD34 HSCT Procedure: Peripheral Blood Stem Cell Transplantation--AHSCT Biological: T Cell-Depleted Hematopoietic Stem Cell Transplantation Biological: Tetanus Toxoid Vaccine Biological: Therapeutic Autologous Lymphocytes Biological: Trivalent Influenza Vaccine Biological: XBP1-US/XBP1-SP/CD138/CS1 Multipeptide Vaccine PVX-410 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Enhancing Anti-Myeloma Vaccine Response After Autologous Stem Cell Transplantation
Actual Study Start Date : May 2016
Estimated Primary Completion Date : December 1, 2018
Estimated Study Completion Date : December 1, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Arm I (vaccines, CD34 transplant, DLI)
ARM 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.
Drug: Melphalan
Given IV
Other Names:
  • Alkeran
  • L-PAM
  • L-Phenylalanine Mustard
  • Phenylalanine Mustard
  • Sarcolysin

Procedure: Peripheral Blood Stem Cell Transplantation--CD34 HSCT
Undergo autologous CD34 HSCT
Other Names:
  • PBPC Transplantation
  • Peripheral Blood Progenitor Cell Transplantation
  • Peripheral Stem Cell Support
  • Peripheral Stem Cell Transplantation

Biological: T Cell-Depleted Hematopoietic Stem Cell Transplantation
Undergo autologous CD34 HSCT

Biological: Tetanus Toxoid Vaccine
Given IM
Other Names:
  • Tetanus Toxoid
  • TT

Biological: Therapeutic Autologous Lymphocytes
Via infusion
Other Name: Autologous T-cells

Biological: Trivalent Influenza Vaccine
Given IM
Other Names:
  • Flu prophylaxis
  • Flu shot
  • Flu vaccination
  • Fluzone
  • Influenza Vaccine

Biological: XBP1-US/XBP1-SP/CD138/CS1 Multipeptide Vaccine PVX-410
Given SC
Other Name: PVX-410

Active Comparator: Arm II (vaccines, stem cell transplant)
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 AHSCT on day 0.
Drug: Melphalan
Given IV
Other Names:
  • Alkeran
  • L-PAM
  • L-Phenylalanine Mustard
  • Phenylalanine Mustard
  • Sarcolysin

Procedure: Peripheral Blood Stem Cell Transplantation--AHSCT
Undergo AHSCT
Other Names:
  • PBPC transplantation
  • Peripheral Blood Progenitor Cell Transplantation
  • Peripheral Stem Cell Support
  • Peripheral Stem Cell Transplantation

Biological: Tetanus Toxoid Vaccine
Given IM
Other Names:
  • Tetanus Toxoid
  • TT

Biological: Trivalent Influenza Vaccine
Given IM
Other Names:
  • Flu prophylaxis
  • Flu shot
  • Flu vaccination
  • Fluzone
  • Influenza Vaccine

Biological: XBP1-US/XBP1-SP/CD138/CS1 Multipeptide Vaccine PVX-410
Given SC
Other Name: PVX-410




Primary Outcome Measures :
  1. Change in influenza antibody titer as measured by hemagglutination inhibition assay (HAI) [ Time Frame: Baseline to 30, 70, 90, and 180 days post-transplant ]
    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 :
  1. Change in absolute lymphocyte count (ALC) [ Time Frame: Baseline to 15 and 30 days post-transplant ]
    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.

  2. Change in immune cells (T cells cluster of differentiation 8 [CD8], CD4) [ Time Frame: Baseline to 15 and 30 days post-transplant ]
    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.

  3. Change in NK cells [ Time Frame: Baseline to up to day 30 ]
    The paired t-test will be employed to test the change in NK cells.

  4. 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 ]
    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.

  5. Changes in absolute monocyte counts (AMC) [ Time Frame: Baseline to 15 and 30 days post-transplant ]
    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.

  6. Engraftment time [ Time Frame: Up to 180 days post-transplant ]
    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.

  7. 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 ]
    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.

  8. 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 ]
    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.

  9. Incidence of infections [ Time Frame: Up to 180 days post-transplant ]
    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.

  10. Progression-free survival [ Time Frame: Up to 2 years post-transplant ]
    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.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02700841


Locations
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United States, Georgia
Emory University/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
OncoPep, Inc.
Investigators
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Principal Investigator: Zaid Al-Kadhimi, MD Emory University/Winship Cancer Institute

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Responsible Party: Zaid Al-Kadhimi, Associate Professor, Emory University
ClinicalTrials.gov Identifier: NCT02700841     History of Changes
Other Study ID Numbers: IRB00079982
NCI-2015-00743 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
WINSHIP2905-15 ( Other Identifier: Emory University/Winship Cancer Institute )
First Posted: March 7, 2016    Key Record Dates
Last Update Posted: February 21, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Melphalan
Mechlorethamine
Vaccines
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Immunosuppressive Agents