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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new vaccine made from weakened Salmonella bacteria to help the immune system fight multiple myeloma, a type of blood cancer. The vaccine, known as CVD908ssb-TXSVN, targets a protein called Survivin, found in most myeloma cancer cells. The trial aims to determine the safest dose, assess potential side effects, and evaluate the vaccine's effectiveness. Individuals with multiple myeloma who have tried at least two standard treatments might be suitable for this study. Participants will receive two doses of the vaccine, administered orally two weeks apart. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new vaccine.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the Salmonella-based vaccine strain, CVD908ssb, has been tested in over 80 healthy individuals as a Salmonella vaccine. These tests used higher doses than those planned for the current study on multiple myeloma patients, suggesting the vaccine might be well-tolerated at lower doses.

Although TXSVN, the modified version of CVD908ssb, has not yet been tested in humans, similar methods have safely targeted the Survivin protein in over 50 cancer patients using immune cells or drugs. Survivin is a protein found in large amounts in cancer cells and is less common in healthy cells.

The current study aims to determine the safest dose of TXSVN for patients. The process begins with a low dose, increasing it only if the initial dose proves safe. If side effects become too severe, doses will be adjusted. This careful approach helps ensure safety as the trial progresses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Most treatments for multiple myeloma involve chemotherapy, corticosteroids, or targeted therapies, which aim to kill cancer cells or prevent their growth. However, CVD908ssb-TXSVN is unique because it's an experimental cancer vaccine derived from a modified strain of Salmonella. This innovative approach leverages the bacteria's natural ability to stimulate the immune system, potentially training it to recognize and attack myeloma cells more effectively. Additionally, this vaccine is administered orally, which is a less invasive method compared to traditional intravenous treatments. Researchers are excited about this treatment's potential to provide a new, immune-based strategy for fighting multiple myeloma.

What evidence suggests that this vaccine might be an effective treatment for multiple myeloma?

Studies have shown that a protein called Survivin is present in over 90% of myeloma cancer cells. Research suggests that targeting Survivin can help the immune system fight these cancer cells. In more than 50 cancer patients, researchers have safely and effectively targeted Survivin using immune cells and other methods. The vaccine TXSVN, which participants in this trial will receive, is designed to trigger an immune response against Survivin and is based on a weakened form of Salmonella. Although TXSVN hasn't been tested in humans yet, the type of Salmonella used has been safely given to over 80 healthy people in previous trials. These findings suggest that TXSVN might help the immune system target and fight multiple myeloma cells. ^{1 2 3 4 5}

Who Is on the Research Team?

Premal Lulla, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03762291

Study Details | NCT03762291 | Multiple Myeloma Trial of ...

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 ...

2.

cancer.gov

cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-01232

A Vaccine (CVD908ssb-TXSVN) Trial for the Treatment of ...

This phase I/II trial tests the safety, side effects, and best dose and whether a cancer vaccine, called CVD908ssb-TXSVN, work to shrink tumors in patients ...

3.

withpower.com

withpower.com/trial/phase-1-multiple-myeloma-7-2021-469be

Salmonella-Based Cancer Vaccine for Multiple Myeloma

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 ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03762291?term=NCT03762291&ra

Multiple Myeloma Trial of Orally Administered 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 ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11331005/

Advances and challenges in anti-cancer vaccines for multiple ...

The vaccine demonstrated promising anti-tumor effects and immunogenicity in prophylactic and therapeutic models of murine MM. The NACH vaccine inhibited tumor ...