Back to resultsSurvivin Vaccine : Multiple Myeloma Autologous Hematopoietic Cell Transplant (HCT)
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Survivin Vaccine
Autologous Hematopoietic Cell Transplantation
Prevnar 13
Granulocyte-colony Stimulating Factor
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Myeloma, Vaccine, Dendritic cell, autologous hematopoietic cell transplant, HCT
Eligibility Criteria
Inclusion Criteria:
Screening:
- As of protocol Version 2 there is no "screening phase".Patients previously consented to the screening phase could still be eligible for treatment if consented for treatment, based upon the updated eligibility criteria.
Treatment:
- Patients with histologically confirmed Multiple Myeloma that are being considered for high dose chemotherapy and autologous stem cell transplant.
- Patients must have a bone marrow biopsy available, or one scheduled to be performed for a clinical indication so that survivin expression could be determined (note: survivin staining in tumor need not be resulted prior to enrollment or treatment as it is obtained for correlative science).
- Patients planned for treatment with high dose melphalan and autologous hematopoietic cell transplant (HCT).
- Complete blood count (CBC) with an absolute neutrophil count (ANC) >= 1,000/uL, hemoglobin >= 8.0 g/dL and platelet count >= 50,000/uL.
- Liver enzymes: total bilirubin less than or equal to 2 mg/dL (>2 mg/dL permitted if the patient has evidence of Gilbert's disease based upon prior bilirubin elevation or genetic testing); Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) less than 1.5 X the upper limit of normal (ULN).
- Signed informed consent form in accordance with institutional and federal law policies.
Exclusion Criteria:
Treatment:
- Patients with Complete Response (CR) or stringent CR after induction therapy as defined by International Response Criteria after most recent therapy.
- Patients with progressive disease at time of transplant.
- Pregnant or lactating woman (as evaluated by serum testing within 48 hours of administration of the first vaccine in women of child bearing potential).
- HIV infection confirmed by nucleic acid tests (NAT).
- Common variable immunodeficiency.
- Active central nervous system (CNS) malignancy.
- Active bacterial, fungal or viral infection.
- Prior history of allogeneic hematopoietic cell transplantation
- Prior malignancy within 5 years of enrollment excluding non-melanoma skin cancer or cervical carcinoma after curative resection, not requiring chemotherapy.
- History of severe allergy (e.g., anaphylaxis) to any component of Prevnar or any diphtheria-toxoid containing vaccine.
Sites / Locations
- H. Lee Moffitt Cancer Center and Research Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Survivin Vaccine and Autologous HCT
Arm Description
Dendritic Cell Survivin Vaccine (DC:AdmS) and Autologous Hematopoietic Cell Transplantation (HCT). Participants will receive 1 pre-transplant survivin vaccine, 7-30 days prior to stem cell apheresis collection. After the first survivin vaccination, participants will be mobilized with Granulocyte-colony Stimulating Factor (G-CSF). A second survivin vaccine will be administered on day +21 (between day+20 and +34) after HCT. All participants will be co-immunized with Prevnar 13 at each time they receive the survivin vaccine.
Outcomes
Primary Outcome Measures
Rate of Complete Response (CR)
Complete Response: A treatment outcome where there are ≤5% plasma cells in the bone marrow and no evidence of myeloma proteins in the serum or urine as measured by standard laboratory techniques.
Number of Participants With Treatment Emergent Adverse Events
The safety of DC:AdmS when administered to patients with myeloma before and at day +21 after autologous hematopoietic stem cell transplant. The approach for assessing potential toxicity of survivin vaccination will focus predominantly on assessing hematopoietic reconstitution, including T cell repopulation and gastrointestinal toxicity. Investigators will also monitor for autoimmune disorders involving other tissues where survivin expression has been demonstrated: these include keratinocytes and melanocytes, myocardium, liver, breast, and brain. The most sensitive test to assess the potential toxicity of survivin vaccination on hematopoietic function is the time of neutrophil repopulation after autologous stem cell transplant (ASCT). Beginning on day of ASCT, participants will be monitored daily for engraftment, defined by an absolute neutrophil count of 500 cells per microliter that is sustained for at least 3 days.
Secondary Outcome Measures
Number of Participants With Improved Immunologic Response
The ability of DC:AdmS to induce T cell immune responses against survivin when administered to patients with myeloma before and at day +21 after autologous hematopoietic stem cell transplant.
Immunologic responses: be measured at baseline prior to the first vaccination (i.e., baseline), after stem cell mobilization and collection (i.e., pre-transplant), and post-transplant at day +60, +90, and +180. Each time 100 cc of peripheral blood will be collected. Immune response evaluations will consist of the following: Determination of the survivin specific T cell frequency using limiting dilution analysis and freely available online software; Analysis of Interferon-γ producing T cells in ELISPOT assays in response to DC loaded survivin peptide pool; Measurement of anti-pneumococcal immunoglobulin G (IgG) antibody titers and T cell responses against cross-reacting material (CRM) adjuvant; Evaluation of immunomodulatory phenotypes by T cell subsets before and after vaccination.
Full Information
NCT ID
NCT02851056
First Posted
July 28, 2016
Last Updated
November 10, 2022
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
1. Study Identification
Unique Protocol Identification Number
NCT02851056
Brief Title
Survivin Vaccine : Multiple Myeloma Autologous Hematopoietic Cell Transplant (HCT)
Official Title
Evaluating the Safety and Biological Activity of a Dendritic Cell Survivin Vaccine in Patients With Multiple Myeloma Undergoing Autologous Hematopoietic Cell Transplantation
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
September 27, 2016 (Actual)
Primary Completion Date
July 16, 2018 (Actual)
Study Completion Date
August 9, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to test what effects (good and bad) a new cancer vaccine will have on participants and their cancer, when administered before and after their autologous hematopoietic cell transplant (HCT).
The name of the vaccine is called Dendritic Cell Survivin Vaccine (DC:AdmS). The vaccine is made using the participant's own blood cells. The vaccine will contain a virus called an adenovirus, similar the virus that causes the common cold. The virus has been changed so it cannot infect humans and cause infections. The vaccine will be prepared at Moffitt Cancer Center in the Cell Therapy Laboratory Facility.
Detailed Description
This study is designed to test the safety and efficacy of the survivin vaccine, as well as the biological activity. A total sample size of 30 patients will be used for the study. In the 1st stage, 10 patients will be used to evaluate the safety and futility of the vaccine. If it passes the 1st stage, investigators will enroll another 20 patients (as 2nd stage) to evaluate the efficacy. The two- stage experiment is based on Simon minmax two-stage design for efficacy. Vaccine will be administered in two stages. After the first survivin vaccination, participants will be mobilized with G-CSF and both in vivo-primed T cells and stem cells will be collected in the same apheresis (the graft). T cells and the CD34 progenitor cells will be transferred back to the participant at the time of autologous graft infusion. Participants will receive re-vaccination on, or near, day 21 after transplant.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Myeloma, Vaccine, Dendritic cell, autologous hematopoietic cell transplant, HCT
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Survivin Vaccine and Autologous HCT
Arm Type
Experimental
Arm Description
Dendritic Cell Survivin Vaccine (DC:AdmS) and Autologous Hematopoietic Cell Transplantation (HCT). Participants will receive 1 pre-transplant survivin vaccine, 7-30 days prior to stem cell apheresis collection. After the first survivin vaccination, participants will be mobilized with Granulocyte-colony Stimulating Factor (G-CSF). A second survivin vaccine will be administered on day +21 (between day+20 and +34) after HCT. All participants will be co-immunized with Prevnar 13 at each time they receive the survivin vaccine.
Intervention Type
Biological
Intervention Name(s)
Survivin Vaccine
Intervention Description
Pre-transplant vaccination : The target dose of Survivin+ Dendritic cells (survivin+, CD11c+, Human Leukocyte Antigen - antigen D Related (HLA-DR)+ by flow-cytometry) is 15 x 10^6 cells. A minimum of 1 x 10^6 cells and a maximum of 20 x 10^6 cells will be administered.
Post-transplant vaccination: The target dose of Survivin+ Dendritic cells (survivin+, CD11c+, HLA-DR+ by flow-cytometry) is 15 x 10^6 cells. A minimum of 1 x 10^6 cells and a maximum of 20 x 10^6 cells will be administered.
Intervention Type
Procedure
Intervention Name(s)
Autologous Hematopoietic Cell Transplantation
Other Intervention Name(s)
HCT
Intervention Description
The participant's own cells are collected from their blood, frozen, and then given back to them after they receive chemotherapy.
Intervention Type
Biological
Intervention Name(s)
Prevnar 13
Other Intervention Name(s)
PCV13
Intervention Description
13-Valent Pneumococcal Conjugate Vaccine (PCV13, Prevnar13). Co-Immunization: All participants will be co-immunized with Prevnar at each time they receive the survivin vaccine. This vaccine will be administered intramuscular (IM) 0.5cc.
Intervention Type
Drug
Intervention Name(s)
Granulocyte-colony Stimulating Factor
Other Intervention Name(s)
G-CSF
Intervention Description
After the first survivin vaccination, participants will be mobilized with G-CSF.
Primary Outcome Measure Information:
Title
Rate of Complete Response (CR)
Description
Complete Response: A treatment outcome where there are ≤5% plasma cells in the bone marrow and no evidence of myeloma proteins in the serum or urine as measured by standard laboratory techniques.
Time Frame
90 days post treatment
Title
Number of Participants With Treatment Emergent Adverse Events
Description
The safety of DC:AdmS when administered to patients with myeloma before and at day +21 after autologous hematopoietic stem cell transplant. The approach for assessing potential toxicity of survivin vaccination will focus predominantly on assessing hematopoietic reconstitution, including T cell repopulation and gastrointestinal toxicity. Investigators will also monitor for autoimmune disorders involving other tissues where survivin expression has been demonstrated: these include keratinocytes and melanocytes, myocardium, liver, breast, and brain. The most sensitive test to assess the potential toxicity of survivin vaccination on hematopoietic function is the time of neutrophil repopulation after autologous stem cell transplant (ASCT). Beginning on day of ASCT, participants will be monitored daily for engraftment, defined by an absolute neutrophil count of 500 cells per microliter that is sustained for at least 3 days.
Time Frame
Up to 6 months post treatment
Secondary Outcome Measure Information:
Title
Number of Participants With Improved Immunologic Response
Description
The ability of DC:AdmS to induce T cell immune responses against survivin when administered to patients with myeloma before and at day +21 after autologous hematopoietic stem cell transplant.
Immunologic responses: be measured at baseline prior to the first vaccination (i.e., baseline), after stem cell mobilization and collection (i.e., pre-transplant), and post-transplant at day +60, +90, and +180. Each time 100 cc of peripheral blood will be collected. Immune response evaluations will consist of the following: Determination of the survivin specific T cell frequency using limiting dilution analysis and freely available online software; Analysis of Interferon-γ producing T cells in ELISPOT assays in response to DC loaded survivin peptide pool; Measurement of anti-pneumococcal immunoglobulin G (IgG) antibody titers and T cell responses against cross-reacting material (CRM) adjuvant; Evaluation of immunomodulatory phenotypes by T cell subsets before and after vaccination.
Time Frame
180 days (6 months) post vaccination
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Screening:
As of protocol Version 2 there is no "screening phase".Patients previously consented to the screening phase could still be eligible for treatment if consented for treatment, based upon the updated eligibility criteria.
Treatment:
Patients with histologically confirmed Multiple Myeloma that are being considered for high dose chemotherapy and autologous stem cell transplant.
Patients must have a bone marrow biopsy available, or one scheduled to be performed for a clinical indication so that survivin expression could be determined (note: survivin staining in tumor need not be resulted prior to enrollment or treatment as it is obtained for correlative science).
Patients planned for treatment with high dose melphalan and autologous hematopoietic cell transplant (HCT).
Complete blood count (CBC) with an absolute neutrophil count (ANC) >= 1,000/uL, hemoglobin >= 8.0 g/dL and platelet count >= 50,000/uL.
Liver enzymes: total bilirubin less than or equal to 2 mg/dL (>2 mg/dL permitted if the patient has evidence of Gilbert's disease based upon prior bilirubin elevation or genetic testing); Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) less than 1.5 X the upper limit of normal (ULN).
Signed informed consent form in accordance with institutional and federal law policies.
Exclusion Criteria:
Treatment:
Patients with Complete Response (CR) or stringent CR after induction therapy as defined by International Response Criteria after most recent therapy.
Patients with progressive disease at time of transplant.
Pregnant or lactating woman (as evaluated by serum testing within 48 hours of administration of the first vaccine in women of child bearing potential).
HIV infection confirmed by nucleic acid tests (NAT).
Common variable immunodeficiency.
Active central nervous system (CNS) malignancy.
Active bacterial, fungal or viral infection.
Prior history of allogeneic hematopoietic cell transplantation
Prior malignancy within 5 years of enrollment excluding non-melanoma skin cancer or cervical carcinoma after curative resection, not requiring chemotherapy.
History of severe allergy (e.g., anaphylaxis) to any component of Prevnar or any diphtheria-toxoid containing vaccine.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frederick Locke, M.D.
Organizational Affiliation
H. Lee Moffitt Cancer Center and Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
12. IPD Sharing Statement
Links:
URL
https://moffitt.org/clinical-trials-research/
Description
Moffitt Cancer Center Clinical Trials website
Learn more about this trial
Survivin Vaccine : Multiple Myeloma Autologous Hematopoietic Cell Transplant (HCT)
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