Salmonella-Based Cancer Vaccine for Multiple Myeloma

(MAPSS Trial)

Overseen By Wendy Callejas

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: Systemic corticosteroids

Disqualifiers: Severe infection, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 11

Duration: 4 weeks

Trial Summary

What is the purpose of this trial?

This trial tests a new cancer vaccine called TXSVN, made from a weakened Salmonella bacteria, in patients with multiple myeloma. The vaccine aims to boost the immune system to fight cancer cells by targeting a specific protein found in these cells. The study will determine the safest dose and monitor side effects and effectiveness.

Will I have to stop taking my current medications?

The trial requires that you stop taking any other investigational therapy for one month and anti-bacterial therapy for 14 days before starting. You also need to be off conventional therapy for at least 1 week before joining, except for immunomodulator drugs.

What data supports the effectiveness of the treatment CVD908ssb-TXSVN for multiple myeloma?

Research shows that Salmonella-based vaccines can activate the body's immune cells to fight cancer, as seen in studies where they helped control tumor growth and even caused tumor regression in different cancer models. This suggests that similar approaches, like the CVD908ssb-TXSVN treatment, might also be effective in treating multiple myeloma by boosting the immune response against cancer cells. ^{1 2 3 4 5}

Is the Salmonella-based cancer vaccine generally safe for humans?

Research on Salmonella-based cancer vaccines, using attenuated (weakened) strains, shows they are not toxic to mice and can effectively stimulate immune responses. While these studies are promising, they primarily involve animal models, so more research is needed to confirm safety in humans. ^{2 3 4 6 7}

How does the treatment CVD908ssb-TXSVN differ from other treatments for multiple myeloma?

This treatment is unique because it uses a weakened form of Salmonella bacteria to deliver cancer-fighting agents directly into the body's immune cells, helping them recognize and attack cancer cells. Unlike traditional treatments, it is administered orally and aims to stimulate a strong immune response against the cancer. ^{1 2 4 6 8}

Research Team

Premal Lulla, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for adults over 18 with multiple myeloma who've had at least two prior treatments, including possibly a stem cell transplant. They must be able to swallow medication, have decent organ function and blood counts, not be pregnant or breastfeeding, and agree to use effective birth control. Those with severe infections or on high-dose steroids can't join.

Inclusion Criteria

My bilirubin levels are normal or slightly high, and my hemoglobin is at least 7.0.

My kidney function, measured by creatinine, is within twice the normal limit for my age.

Patients with life expectancy greater than or equal to 6 weeks

Exclusion Criteria

Pregnant or breast feeding

People in your household who are pregnant, have a weak immune system, or are under 2 years old.

I am HIV positive.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive two doses of the TXSVN vaccine, two weeks apart, with monitoring for side effects and disease assessment

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including blood and stool cultures, and imaging studies

8 weeks

Weekly visits (in-person) for 8 weeks

Long-term follow-up

Participants are contacted annually for up to 4 additional years to evaluate long-term disease response

4 years

Annual contact

Treatment Details

Interventions

• CVD908ssb-TXSVN

Trial Overview The study tests TXSVN, an investigational cancer vaccine derived from genetically modified Salmonella that targets Survivin in cancer cells. It aims to find the highest safe dose of TXSVN, understand side effects, and assess its potential effectiveness against multiple myeloma.

Participant Groups

Group I: CVD908ssb-TXSVN Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Findings from Research

The attenuated strain of Salmonella typhimurium, SL3235, demonstrated significant antitumor activity against a rapidly growing murine plasmacytoma, TEPC-183, leading to prolonged survival in tumor-bearing mice when administered intralesionally or intraperitoneally.

The effectiveness of the Salmonella treatment was influenced by the timing of administration and the dosage, with lower doses proving more effective than higher doses, suggesting a potential for this genetically engineered strain as a novel immunotherapeutic agent in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy of a plasmacytoma with attenuated salmonella. Eisenstein, TK., Bushnell, B., Meissler, JJ., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Tumor relapse prevented by combining adoptive T cell therapy with Salmonella typhimurium. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Effective cancer vaccine platform based on attenuated salmonella and a type III secretion system. [2021]

3. England pubmed.ncbi.nlm.nih.gov

A therapeutic vaccine using Salmonella-modified tumor cells combined with interleukin-2 induces enhanced antitumor immunity in B-cell lymphoma. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Combining DNA Vaccine and AIDA-1 in Attenuated Salmonella Activates Tumor-Specific CD4+ and CD8+ T-cell Responses. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

Intra-tumoral Salmonella typhimurium induces a systemic anti-tumor immune response that is directed by low-dose radiation to treat distal disease. [2008]

6. United States pubmed.ncbi.nlm.nih.gov

Novel cancer vaccine based on genes of Salmonella pathogenicity island 2. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Recombinant Salmonella-based 4-1BBL vaccine enhances T cell immunity and inhibits the development of colorectal cancer in rats: in vivo effects of vaccine containing 4-1BBL. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Immunotherapy of a plasmacytoma with attenuated salmonella. [2019]