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

NCT ID: NCT02851056

Last Updated: 2022-11-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-27
• Study Completion Date: 2018-08-09

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Survivin Vaccine

Intervention Type: BIOLOGICAL

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.

Autologous Hematopoietic Cell Transplantation

Intervention Type: PROCEDURE

The participant's own cells are collected from their blood, frozen, and then given back to them after they receive chemotherapy.

Prevnar 13

Intervention Type: BIOLOGICAL

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.

Granulocyte-colony Stimulating Factor

Intervention Type: DRUG

After the first survivin vaccination, participants will be mobilized with G-CSF.

Interventions

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.

Intervention Type: BIOLOGICAL

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.

Intervention Type: PROCEDURE

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.

Intervention Type: BIOLOGICAL

Granulocyte-colony Stimulating Factor

After the first survivin vaccination, participants will be mobilized with G-CSF.

Intervention Type: DRUG

Other Intervention Names

HCT; PCV13; G-CSF

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Frederick Locke, M.D.

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Countries

United States

References

Freeman CL, Atkins R, Varadarajan I, Menges M, Edelman J, Baz R, Brayer J, Castaneda Puglianini O, Ochoa-Bayona JL, Nishihori T, Shain KH, Shah B, Chen DT, Kelley L, Coppola D, Alsina M, Antonia S, Anasetti C, Locke FL. Survivin Dendritic Cell Vaccine Safely Induces Immune Responses and Is Associated with Durable Disease Control after Autologous Transplant in Patients with Myeloma. Clin Cancer Res. 2023 Nov 14;29(22):4575-4585. doi: 10.1158/1078-0432.CCR-22-3987.

Reference Type: DERIVED

PMID: 37735756 (View on PubMed)

Other Identifiers

MCC-18346

Identifier Type: -

Identifier Source: org_study_id