Multiple Myeloma Trial of Orally Administered Salmonella Based Survivin Vaccine

NCT03762291 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: H-42712 MAPSS
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Multiple myeloma patients will receive a cancer vaccine, called TXSVN that has been derived from the bacteria Salmonella. TXSVN is a weakened form of a live vaccine strain of the Salmonella bacteria (also known as the CVD908ssb strain) that has been genetically modified in the laboratory to produce a protein known as Survivin that stimulates an immune response in the body to the Survivin tumor antigen. CVD908ssb has been administered to over 80 healthy donors as a Salmonella vaccine in reported clinical trials. This trial intends to explore administration of this vaccine at a lower dose than what was tested in healthy individuals. Survivin belongs to the group of proteins known as tumor-associated antigens (TAAs). These are cell proteins that are specific to the cancer cell. They either are not found or are found in low levels normal cells in the human body. More than 90% of myeloma cancer cells have been shown to possess large quantities of Survivin. TXSVN may activate the immune system which is your body's ability to fight disease, and help develop a response against cancer cells that express Survivin. Survivin has been safely targeted using immune cells, drugs or direct inhibitors in over 50 patients with cancers in published reports. TXSVN, the modified strain of CVD908ssb has not been tested in humans to this date. TXSVN is an investigational product not approved by the U.S. Food and Drug Administration. The purpose of this study is to find the largest safe dose of TXSVN, to learn what the side effects are, and to see whether this therapy might help participants with multiple myeloma.

Conditions

Multiple Myeloma

Keywords

hematologic malignancy; malignant proliferation of plasma cells; MM

Outcome Measures

Primary Outcomes (1)

• Number of patients with dose limiting toxicity (DLT) by CTCAE, v5.0

  Incidence of dose limiting toxicities (DLT) of CVD908ssb-TXSVN vaccine in patients with multiple myeloma.

  8 weeks

Secondary Outcomes (1)

• Overall response rate according to the modified International Myeloma Working Group (IMWG) Uniform Response criteria.

  8 weeks

Study Arms (1)

CVD908ssb-TXSVN

EXPERIMENTAL

3 different dosing schedules will be studied (3+3 design). At the beginning, patients will start on the lowest dose (1 of 3 different levels) of TXSVN. Once that dose schedule proves safe, the next group of patients will be started at a higher dose. This process will continue until all 3 dose levels are studied. If the side-effects are too severe, the dose will be lowered or the TXSVN administrations will be stopped. Each patient will receive 2 vaccinations at the same dose, 2 weeks apart, according to the following dosing schedules: The administration will be oral. Dose Level 1 Day 0: 2 x 10\^5 cfu Day 14: 2 x 10\^5 cfu Dose Level 2 Day 0: 2 x 10\^6 cfu Day 14: 2 x 10\^6 cfu Dose Level 3 Day 0: 2 x 10\^7 cfu Day 14: 2 x 10\^7 cfu

Biological: CVD908ssb-TXSVN

Interventions

CVD908ssb-TXSVN BIOLOGICAL

TXSVN may activate the immune system which is the participants body's ability to fight disease, and help develop a response against cancer cells that express Survivin. Survivin has been safely targeted using immune cells, drugs or direct inhibitors in over 50 patients with cancers in published reports. Survivin belongs to the group of proteins known as tumor-associated antigens (TAAs). These are cell proteins that are specific to the cancer cell. They either are not found or are found in low levels normal cells in the human body. More than 90% of myeloma cancer cells have been shown to possess large quantities of Survivin.

Also known as: TXSVN

CVD908ssb-TXSVN

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Any patient, greater than or equal to 18 yrs old regardless of sex, with a diagnosis of Myeloma after receiving at least two lines of conventional therapy which can include an autologous HSCT. If a patient has received an autologous or syngeneic SCT they must be greater than 90 days post-transplant
• Patients with life expectancy greater than or equal to 6 weeks.
• Pulse oximetry of greater than 90% on room air in patients who previously received radiation therapy to the chest. This is not required in patients who have not received radiation therapy to the chest in the past.
• Patients with a Karnofsky score of greater than or equal to 50
• Patients with bilirubin less than or equal to 2x upper limit of normal and Hgb greater than or equal to 7.0 (transfusion allowed).
• AST less than or equal to 3x upper limit of normal.
• ANC greater than 1000 at the time of vaccination and an ALC greater than 500.
• Patients with a creatinine less than or equal to 2x upper limit of normal for age.
• Patients should have been off other investigational therapy for one month prior to entry in this study.
• Patients should be off anti-bacterial therapy for 14 days prior to vaccination
• Patients should have been off conventional therapy for at least 1 week prior to entry in this study except immunomodulator drugs
• Informed consent explained to, understood by and signed by patient. Patient given copy of informed consent.
• Due to unknown effects of this therapy on a fetus, pregnant women are excluded from this research. The male partner should use a condom. Females of child-bearing potential must be willing to utilize one of the more effective birth control methods during the study unless female has had a hysterectomy or tubal ligation.
• Ability to swallow medications

You may not qualify if:

• Severe intercurrent infection.
• Patients receiving greater than 0.5 mg/kg/day (prednisone equivalent) of systemic corticosteroids
• Pregnant or breast feeding.
• Grade II or higher nausea, vomiting or diarrhea.
• History of allergy to prior vaccination with a Salmonella vaccine
• HIV infection
• Unable to tolerate Salmonella directed antibiotics
• Household contacts who are immunocompromised, pregnant or under 2 years of age.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• The Methodist Hospital Research Institute: collaborator

Study Sites (1)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site

Study Officials

• Premal Lulla, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professsor, Center for Cell and Gene Therapy

Study Record Dates

• First Submitted: September 11, 2018
• First Posted: December 3, 2018
• Study Start: August 6, 2021
• Primary Completion: March 22, 2022
• Study Completion: August 5, 2024
• Last Updated: February 5, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)