Survivin Vaccine : Multiple Myeloma Autologous Hematopoietic Cell Transplant (HCT)

• ClinicalTrials.gov Identifier: NCT02851056
• Recruitment Status: Completed
• First Posted: August 1, 2016
• Last Update Posted: November 14, 2022
• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Information provided by (Responsible Party): H. Lee Moffitt Cancer Center and Research Institute

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.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Biological: Survivin Vaccine; Procedure: Autologous Hematopoietic Cell Transplantation; Biological: Prevnar 13; Drug: Granulocyte-colony Stimulating Factor	Early Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluating the Safety and Biological Activity of a Dendritic Cell Survivin Vaccine in Patients With Multiple Myeloma Undergoing Autologous Hematopoietic Cell Transplantation
• Actual Study Start Date: September 27, 2016
• Actual Primary Completion Date: July 16, 2018
• Actual Study Completion Date: August 9, 2018

Arms and Interventions

Arm

Intervention/treatment

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.

Biological: Survivin Vaccine; 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.; Procedure: Autologous Hematopoietic Cell Transplantation; The participant's own cells are collected from their blood, frozen, and then given back to them after they receive chemotherapy.; Other Name: HCT; Biological: Prevnar 13; 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 Name: PCV13; Drug: Granulocyte-colony Stimulating Factor; After the first survivin vaccination, participants will be mobilized with G-CSF.; Other Name: G-CSF

Outcome Measures

Primary Outcome Measures :

1. Rate of Complete Response (CR) [ Time Frame: 90 days post treatment ]
   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.
2. Number of Participants With Treatment Emergent Adverse Events [ Time Frame: Up to 6 months post treatment ]
   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 :

1. Number of Participants With Improved Immunologic Response [ Time Frame: 180 days (6 months) post vaccination ]

   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Florida

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States, 33612

Sponsors and Collaborators

H. Lee Moffitt Cancer Center and Research Institute

Investigators

• Principal Investigator: Frederick Locke, M.D.; H. Lee Moffitt Cancer Center and Research Institute

More Information

Additional Information:

Moffitt Cancer Center Clinical Trials website 

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT02851056
• Other Study ID Numbers: MCC-18346
• First Posted: August 1, 2016
• Last Update Posted: November 14, 2022
• Last Verified: November 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:

Myeloma; Vaccine; Dendritic cell; autologous hematopoietic cell transplant; HCT

Additional relevant MeSH terms:

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; Lenograstim; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs