- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02851056
Survivin Vaccine : Multiple Myeloma Autologous Hematopoietic Cell Transplant (HCT)
Evaluating the Safety and Biological Activity of a Dendritic Cell Survivin Vaccine in Patients With Multiple Myeloma Undergoing Autologous Hematopoietic Cell Transplantation
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.
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
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Florida
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Tampa, Florida, United States, 33612
- H. Lee Moffitt Cancer Center and Research Institute
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Survivin Vaccine and Autologous HCT
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.
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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.
The participant's own cells are collected from their blood, frozen, and then given back to them after they receive chemotherapy.
Other Names:
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.
Other Names:
After the first survivin vaccination, participants will be mobilized with G-CSF.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of Complete Response (CR)
Time Frame: 90 days post treatment
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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.
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90 days post treatment
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Number of Participants With Treatment Emergent Adverse Events
Time Frame: Up to 6 months post treatment
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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.
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Up to 6 months post treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants With Improved Immunologic Response
Time Frame: 180 days (6 months) post vaccination
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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. |
180 days (6 months) post vaccination
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Collaborators and Investigators
Investigators
- Principal Investigator: Frederick Locke, M.D., H. Lee Moffitt Cancer Center and Research Institute
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Physiological Effects of Drugs
- Immunologic Factors
- Adjuvants, Immunologic
- Lenograstim
Other Study ID Numbers
- MCC-18346
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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