IL-2 Expressing, Attenuated Salmonella Typhimurium in Unresectable Hepatic Spread

• Sponsor: Masonic Cancer Center, University of Minnesota (Other)
• Overall Status: Completed
• CT.gov ID: NCT01099631
• Collaborator: (none)
• Enrollment: 22
• Location: 1
• Arms: 6
• Duration (Months): 50
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The working hypothesis is that oral administration of an attenuated strain of Salmonella typhimurium is safe and efficacious for patients with unresectable hepatic metastasis from a solid tumor cancer. The primary objective of the study is to determine the MTD of Salmonella typhimurium in the treatment.

Condition or Disease	Intervention/Treatment	Phase
Cancer of the Liver; Liver Cancer; Hepatoma; Liver Neoplasms; Biliary Cancer	Biological: Salmonella typhimurium	Phase 1

Detailed Description

This phase I study will be done to evaluate a dose escalation scheme of oral administration of an attenuated strain of Salmonella typhimurium expressing human interleukin-2 (IL-2) in patients with unresectable hepatic metastases from a solid tumor cancer. Standard Phase I dose escalation scheme will be used to determine the MTD of Salmonella Typhimurium. Six dose levels of Salmonella will be studied with a minimum of 3 patients enrolled in a dose level.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study of an IL-2 Expressing, Attenuated Salmonella Typhimurium in Patients With Unresectable Hepatic Spread From Any Non-Hematologic Primary
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Salmonella typhimurium 10 to the 5th - Level 1 Patients will receive (a minimum of 3 patients) escalating doses of Salmonella typhimurium to achieve a maximum tolerated dose (MTD).	Biological: Salmonella typhimurium; Attenuated Salmonella typhimurium (virulent strain x4550) will be given orally in escalating dose groups: Level 1 = 10^5, Level 2 = 10^6, Level 3 = 10^7, Level 4 = 10^8, Level 5 = 10^9, Level 6 = 10^10.
Experimental: Salmonella typhimurium 10 to the 6th -- Level 2 Patients will receive (a minimum of 3 patients) escalating doses of Salmonella typhimurium to achieve a maximum tolerated dose (MTD).	Biological: Salmonella typhimurium; Attenuated Salmonella typhimurium (virulent strain x4550) will be given orally in escalating dose groups: Level 1 = 10^5, Level 2 = 10^6, Level 3 = 10^7, Level 4 = 10^8, Level 5 = 10^9, Level 6 = 10^10.
Experimental: Salmonella typhimurium 10 to the 7th -- Level 3 Patients will receive (a minimum of 3 patients) escalating doses of Salmonella typhimurium to achieve a maximum tolerated dose (MTD).	Biological: Salmonella typhimurium; Attenuated Salmonella typhimurium (virulent strain x4550) will be given orally in escalating dose groups: Level 1 = 10^5, Level 2 = 10^6, Level 3 = 10^7, Level 4 = 10^8, Level 5 = 10^9, Level 6 = 10^10.
Experimental: Salmonella typhimurium 10 to the 8th - Level 4 Patients will receive (a minimum of 3 patients) escalating doses of Salmonella typhimurium to achieve a maximum tolerated dose (MTD).	Biological: Salmonella typhimurium; Attenuated Salmonella typhimurium (virulent strain x4550) will be given orally in escalating dose groups: Level 1 = 10^5, Level 2 = 10^6, Level 3 = 10^7, Level 4 = 10^8, Level 5 = 10^9, Level 6 = 10^10.
Experimental: Salmonella typhimurium 10 to the 9th - Level 5 Patients will receive (a minimum of 3 patients) escalating doses of Salmonella typhimurium to achieve a maximum tolerated dose (MTD).	Biological: Salmonella typhimurium; Attenuated Salmonella typhimurium (virulent strain x4550) will be given orally in escalating dose groups: Level 1 = 10^5, Level 2 = 10^6, Level 3 = 10^7, Level 4 = 10^8, Level 5 = 10^9, Level 6 = 10^10.
Experimental: Salmonella typhimurium 10 to the 10th - Level 1 Patients will receive (a minimum of 3 patients) escalating doses of Salmonella typhimurium to achieve a maximum tolerated dose (MTD).	Biological: Salmonella typhimurium; Attenuated Salmonella typhimurium (virulent strain x4550) will be given orally in escalating dose groups: Level 1 = 10^5, Level 2 = 10^6, Level 3 = 10^7, Level 4 = 10^8, Level 5 = 10^9, Level 6 = 10^10.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Dose Limiting Events to Determine the Maximum Tolerated Dose (MTD) of Salmonella Typhimurium [Up to 24 Weeks After Dose of Salmonella typhimurium]

   Maximum tolerated dose will be determined by the number of patients with Dose limiting toxicity (DLT) at a given dose level. DLT is defined as treatment related: Sepsis (salmonella) syndrome, Grade 4 vomiting or diarrhea, Other grade 3 or greater toxicity. If > or = 2 patients at a dose level has a DLT, this level will be declared the MTD.

Secondary Outcome Measures

1. Number of Participants With Complete Response to Treatment [8 Weeks After Treatment with Salmonella Typhimurium]

   Evaluation is performed using Response Evaluation Criteria in Solid Tumors (RECIST). Each patient will be assigned one of the following categories: Complete response (CR) the disappearance of all target lesion; Partial response (PR) at least a 30% decrease; Progressive disease (PD) at least a 20% increase, or the appearance of one or more new lesions; Stable disease (SD) neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease; early death from malignant disease; unknown (insufficient evaluation to determine response status).

2. Peripheral Blood NK Cells Count [Baseline and 5 Weeks After Dosing with Salmonella typhimurium]

   Patients receiving doses of 10^5 through 10^10 Colony forming units of Salmonella typhimurium had their peripheral blood flow cytometry performed to identify the NK (Natural killer) cells population (CD8-, CD4-, CD49b+) prior to administration and at 5 weeks post administration. The flow cytometry data below was gathered by gating on the lymphocyte population of cells in the patient's blood, as determined by FSC vs. SSC. The mean percentage of NK cells in sample's lymphocyte population is given.

3. Peripheral Blood T Cells Count [Baseline and 5 Weeks After Dosing with Salmonella typhimurium]

   Patients receiving doses of 10^5 through 10^10 Colony forming units of Salmonella typhimurium had their peripheral blood flow cytometry performed to identify the NK (Natural killer) cells population (CD25+, FoxP3+) prior to administration and at 5 weeks post administration. The flow cytometry data below was gathered by gating on the lymphocyte population of cells in the patient's blood, as determined by FSC vs. SSC. The mean percentage of T cells in sample's lymphocyte population is given.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologic documentation of malignancy (any solid tumor type) that has spread to the liver and deemed unresectable, and for which no effective standard therapies are available. Patients with additional disease outside of the liver will be allowed.

• Patients may have received any number of other prior therapies; however at least 3 weeks must have passed since last dose of chemotherapy or radiotherapy (6 weeks for Nitrosoureas or Mitomycin C) prior to study entry.

• Must have recovered from all acute toxicities (defined per National Cancer Institute's Common Toxicity Criteria for Adverse Events 3.0 ≤ grade 1) associated with previous treatment.

• Eastern Cooperative Oncology Group (ECOG) performance status ≤2.

• Life expectancy of greater than 2 months as determined by the enrolling investigator

• Adequate organ function within 1 week of treatment start defined as:

• Adequate bone marrow reserve: leukocytes ≥ 3,000/μl, absolute neutrophil count (ANC) ≥ 1,500/μl, platelets ≥ 100,000/μl

• Hepatic: bilirubin ≤1.5 times institutional upper limit of normal (×ULN), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN

• Renal: serum creatinine ≤ 1.5 x ULN

• Women of child-bearing potential and sexually active men must agree to use adequate contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

Exclusion Criteria:

• Unable to take oral drugs or clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to: malabsorption syndrome, major resection of stomach or small bowel

• Receiving any other investigational agents

• Known central nervous system metastases

• Residing in a household or having close contact with pregnant women, young children (under the age of 1 year) or immune compromised persons

• Engaged in activities that might pose a risk for widespread dissemination of this organism, including, but not limited to; health care, child care, or food service.

• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations.

• Pregnant or breastfeeding. Women of child bearing potential must have a negative serum or urine pregnancy test within 7 days of prior to the start of treatment. Pregnancy testing is not required for post-menopausal or surgically sterilized women. Breast-feeding mothers will be asked to discontinue feeding infants prior to enrolling in the study.

• Known HIV infection, need for chronic steroids or other immunosuppressant drugs, or other medical conditions that in the investigator's opinion result in a significant degree of immunosuppression. Patients without identified HIV risk factors are not required to have HIV testing to be eligible.

• Known active hepatitis B or C infection

• Known HLA B27

• Have permanent artificial implants (such as, but not limited to prosthetic valves and joints.)

• Any other condition which in the investigator's opinion renders the patient at high risk for overwhelming infection

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Edward W. Greeno, MD	Minneapolis	Minnesota	United States	55455

Sponsors and Collaborators

• Masonic Cancer Center, University of Minnesota

Investigators

• Principal Investigator: Edward W. Greeno, MD, Masonic Cancer Center, University of Minnesota

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT01099631
• Other Study ID Numbers: 2009LS003; 0906M68041; Protocol #0907-991
• First Posted: Apr 7, 2010
• Last Update Posted: Jul 20, 2020
• Last Verified: Jul 1, 2020

• Keywords provided by Masonic Cancer Center, University of Minnesota: Salmonella typhimurium; unresectable hepatic cancer; attenuated Salmonella typhimurium; IL-2
• Additional relevant MeSH terms: Liver Neoplasms

Study Results

Participant Flow

Arm/Group Title	Salmonella Typhimurium 10 to the 5 th - Level 1	Salmonella Typhimurium 10 to the 6 th - Level 2	Salmonella Typhimurium 10 to the 7 th - Level 3	Salmonella Typhimurium 10 to the 8 th - Level 4	Salmonella Typhimurium 10 to the 9th - Level 5	Salmonella Typhimurium 10 to the 10 th - Level 6
Arm/Group Description	Patients received Level 1 = 10^5 dose of of Salmonella typhimurium	Patients received Level 2 = 10^6th dose of Salmonella typhimurium	Patients received Level 3 = 10^7th dose of Salmonella typhimurium	Patients received Level 4 = 10^7th dose of Salmonella typhimurium	Patients received Level 5 = 10^9th dose of Salmonella typhimurium	Patients received Level 6 = 10^10th dose of Salmonella typhimurium
Period Title: Overall Study
STARTED	6	3	3	3	3	4
COMPLETED	6	3	3	3	3	4
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Salmonella Typhimurium 10 to the 5 th - Level 1	Salmonella Typhimurium 10 to the 6 th - Level 2	Salmonella Typhimurium 10 to the 7 th - Level 3	Salmonella Typhimurium 10 to the 8 th - Level 4	Salmonella Typhimurium 10 to the 9 th - Level 5	Salmonella Typhimurium 10 to the 10 th - Level 6	Total
Arm/Group Description	Patients received Level 1 = 10^5th dose of Salmonella typhimurium	Patients received Level 2 = 10^6th dose of Salmonella typhimurium	Patients received Level 3 = 10^7th dose of Salmonella typhimurium	Patients received Level 4 = 10^8th dose of Salmonella typhimurium	Patients received Level 5 = 10^9th dose of Salmonella typhimurium	Patients received Level 6 = 10^10th dose of Salmonella typhimurium	Total of all reporting groups
Overall Participants	6	3	3	3	3	4	22
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	4 66.7%	2 66.7%	2 66.7%	1 33.3%	0 0%	3 75%	12 54.5%
>=65 years	2 33.3%	1 33.3%	1 33.3%	2 66.7%	3 100%	1 25%	10 45.5%
Sex: Female, Male (Count of Participants)
Female	4 66.7%	1 33.3%	1 33.3%	1 33.3%	2 66.7%	2 50%	11 50%
Male	2 33.3%	2 66.7%	2 66.7%	2 66.7%	1 33.3%	2 50%	11 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	6 100%	3 100%	3 100%	3 100%	3 100%	4 100%	22 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	2 66.7%	0 0%	0 0%	1 33.3%	0 0%	3 13.6%
White	6 100%	1 33.3%	3 100%	3 100%	1 33.3%	4 100%	18 81.8%
More than one race	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	1 4.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Dose Limiting Events to Determine the Maximum Tolerated Dose (MTD) of Salmonella Typhimurium
Description	Maximum tolerated dose will be determined by the number of patients with Dose limiting toxicity (DLT) at a given dose level. DLT is defined as treatment related: Sepsis (salmonella) syndrome, Grade 4 vomiting or diarrhea, Other grade 3 or greater toxicity. If > or = 2 patients at a dose level has a DLT, this level will be declared the MTD.
Time Frame	Up to 24 Weeks After Dose of Salmonella typhimurium

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Salmonella Typhimurium 10 to the 5 th - Level 1	Salmonella Typhimurium 10 to the 6 th - Level 2	Salmonella Typhimurium 10 to the 7 th - Level 3	Salmonella Typhimurium 10 to the 8 th - Level 4	Salmonella Typhimurium 10 to the 9th - Level 5	Salmonella Typhimurium 10 to the 10 th - Level 6
Arm/Group Description	Patients received Level 1 = 10^5th dose of Salmonella typhimurium	Patients received Level 2 = 10^6th dose of Salmonella typhimurium	Patients received Level 3 = 10^7th dose of Salmonella typhimurium	Patients received Level 4 = 10^8th dose of Salmonella typhimurium	Patients received Level 5 = 10^9th dose of Salmonella typhimurium	Patients received Level 6 = 10^10th dose of Salmonella typhimurium
Measure Participants	6	3	3	3	3	4
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

2. Secondary Outcome

Title	Number of Participants With Complete Response to Treatment
Description	Evaluation is performed using Response Evaluation Criteria in Solid Tumors (RECIST). Each patient will be assigned one of the following categories: Complete response (CR) the disappearance of all target lesion; Partial response (PR) at least a 30% decrease; Progressive disease (PD) at least a 20% increase, or the appearance of one or more new lesions; Stable disease (SD) neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease; early death from malignant disease; unknown (insufficient evaluation to determine response status).
Time Frame	8 Weeks After Treatment with Salmonella Typhimurium

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Salmonella Typhimurium 10 to the 5 th - Level 1	Salmonella Typhimurium 10 to the 6 th - Level 2	Salmonella Typhimurium 10 to the 7 th - Level 3	Salmonella Typhimurium 10 to the 8 th - Level 4	Salmonella Typhimurium 10 to the 9th - Level 5	Salmonella Typhimurium 10 to the 10 th - Level 6
Arm/Group Description	Patients received Level 1 = 10^5th dose of Salmonella typhimurium	Patients received Level 2 = 10^6th dose of Salmonella typhimurium	Patients received Level 3 = 10^7th dose of Salmonella typhimurium	Patients received Level 4 = 10^8th dose of Salmonella typhimurium	Patients received Level 5 = 10^9th dose of Salmonella typhimurium	Patients received Level 6 = 10^10th dose of Salmonella typhimurium
Measure Participants	6	3	3	3	3	4
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

3. Secondary Outcome

Title	Peripheral Blood NK Cells Count
Description	Patients receiving doses of 10^5 through 10^10 Colony forming units of Salmonella typhimurium had their peripheral blood flow cytometry performed to identify the NK (Natural killer) cells population (CD8-, CD4-, CD49b+) prior to administration and at 5 weeks post administration. The flow cytometry data below was gathered by gating on the lymphocyte population of cells in the patient's blood, as determined by FSC vs. SSC. The mean percentage of NK cells in sample's lymphocyte population is given.
Time Frame	Baseline and 5 Weeks After Dosing with Salmonella typhimurium

Outcome Measure Data

Analysis Population Description

One patient in 10 to the 6 th - Level 2 arm was not evaluable. One patient in 10 to the 7 th - Level 3 arm was not evaluable. Two patients in 10 to the 8 th - Level 4 arm were not evaluable. Two patients in 10 to the 9th - Level 5 arm were not evaluable. Two patients in 10 to the 10th - Level 6 arm were not evaluable.

Arm/Group Title	Salmonella Typhimurium 10 to the 5 th - Level 1	Salmonella Typhimurium 10 to the 6 th - Level 2	Salmonella Typhimurium 10 to the 7 th - Level 3	Salmonella Typhimurium 10 to the 8 th - Level 4	Salmonella Typhimurium 10 to the 9th - Level 5	Salmonella Typhimurium 10 to the 10 th - Level 6
Arm/Group Description	Patients received Level 1 = 10^5th dose of Salmonella typhimurium	Patients received Level 2 = 10^6th dose of Salmonella typhimurium	Patients received Level 3 = 10^7th dose of Salmonella typhimurium	Patients received Level 4 = 10^8 th dose of Salmonella typhimurium	Patients received Level 5 = 10^9th dose of Salmonella typhimurium	Patients received Level 1 = 10^10 th dose of Salmonella typhimurium
Measure Participants	6	2	2	1	1	2
Before administration	10.52 (5.41)	8.2 (2.55)	17.1 (3.3)	23.5 (0)	19.6 (0)	6.55 (0.49)
After administration	13.75 (5.18)	9.3 (3.54)	19.7 (8.06)	28.8 (0)	23.9 (0)	5.65 (0.91)

4. Secondary Outcome

Title	Peripheral Blood T Cells Count
Description	Patients receiving doses of 10^5 through 10^10 Colony forming units of Salmonella typhimurium had their peripheral blood flow cytometry performed to identify the NK (Natural killer) cells population (CD25+, FoxP3+) prior to administration and at 5 weeks post administration. The flow cytometry data below was gathered by gating on the lymphocyte population of cells in the patient's blood, as determined by FSC vs. SSC. The mean percentage of T cells in sample's lymphocyte population is given.
Time Frame	Baseline and 5 Weeks After Dosing with Salmonella typhimurium

Outcome Measure Data

Analysis Population Description

One patient in 10 to the 6 th - Level 2 arm was not evaluable. One patient in 10 to the 7 th - Level 3 arm was not evaluable. Two patients in 10 to the 8 th - Level 4 arm were not evaluable. Two patients in 10 to the 9th - Level 5 arm were not evaluable. Two patients in 10 to the 10th - Level 6 arm were not evaluable.

Arm/Group Title	Salmonella Typhimurium 10 to the 5 th - Level 1	Salmonella Typhimurium 10 to the 6 th - Level 2	Salmonella Typhimurium 10 to the 7 th - Level 3	Salmonella Typhimurium 10 to the 8 th - Level 4	Salmonella Typhimurium 10 to the 9th - Level 5	Salmonella Typhimurium 10 to the 10 th - Level 6
Arm/Group Description	Patients received Level 1 = 10^5th dose of Salmonella typhimurium	Patients received Level 2 = 10^6 th dose of Salmonella typhimurium	Patients received Level 3 = 10^7 th dose of Salmonella typhimurium	Patients received Level 4 = 10^8 th dose of Salmonella typhimurium	Patients received Level 5 = 10^10 th dose of Salmonella typhimurium	Patients received Level 6 = 10^10 th dose of Salmonella typhimurium
Measure Participants	6	2	2	1	1	4
Before administration	51.77 (20.04)	50.25 (8.70)	63 (2.82)	56.3 (0)	50.1 (0)	70.6 (7.35)
After administration	53.92 (9.17)	64.25 (8.98)	45.3 (20.85)	42.4 (0)	53.2 (0)	77.65 (1.63)

Adverse Events

Time Frame	6 months
Arm/Group Title	Salmonella Typhimurium 10 to the 5 th - Level 1		Salmonella Typhimurium 10 to the 6 th - Level 2		Salmonella Typhimurium 10 to the 7 th - Level 3		Salmonella Typhimurium 10 to the 8 th - Level 4		Salmonella Typhimurium 10 to the 9 th - Level 5		Salmonella Typhimurium 10 to the 10 th - Level 6
Arm/Group Description	Patients received Level 1 = 10^5th dose of Salmonella typhimurium		Patients received Level 2 = 10^6th dose of Salmonella typhimurium		Patients received Level 3 = 10^7th dose of Salmonella typhimurium		Patients received Level 4 = 10^8th dose of Salmonella typhimurium		Patients received Level 5 = 10^9th dose of Salmonella typhimurium		Patients received Level 6 = 10^10th dose of Salmonella typhimurium
All Cause Mortality
	Salmonella Typhimurium 10 to the 5 th - Level 1		Salmonella Typhimurium 10 to the 6 th - Level 2		Salmonella Typhimurium 10 to the 7 th - Level 3		Salmonella Typhimurium 10 to the 8 th - Level 4		Salmonella Typhimurium 10 to the 9 th - Level 5		Salmonella Typhimurium 10 to the 10 th - Level 6
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/6 (66.7%)		2/3 (66.7%)		3/3 (100%)		3/3 (100%)		2/3 (66.7%)		4/4 (100%)
Serious Adverse Events
	Salmonella Typhimurium 10 to the 5 th - Level 1		Salmonella Typhimurium 10 to the 6 th - Level 2		Salmonella Typhimurium 10 to the 7 th - Level 3		Salmonella Typhimurium 10 to the 8 th - Level 4		Salmonella Typhimurium 10 to the 9 th - Level 5		Salmonella Typhimurium 10 to the 10 th - Level 6
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/6 (33.3%)		1/3 (33.3%)		3/3 (100%)		3/3 (100%)		2/3 (66.7%)		1/4 (25%)
Blood and lymphatic system disorders
Anemia	0/6 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/4 (0%)	0
Gastrointestinal disorders
GI bleeding	0/6 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/4 (25%)	1
Vomiting	0/6 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0
General disorders
Urosepsis	1/6 (16.7%)	1	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/4 (0%)	0
Hepatobiliary disorders
Gallbladder obstruction	0/6 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/4 (0%)	0
hyperkalemia	0/6 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/4 (0%)	0
Investigations
Creatinine increased	1/6 (16.7%)	1	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/4 (0%)	0
Musculoskeletal and connective tissue disorders
New compression fractures	0/6 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign	0/6 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	1	0/3 (0%)	0	0/4 (0%)	0
Tumor pain	0/6 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0
Nervous system disorders
Intracranial hemorrhage	0/6 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/4 (0%)	0
Other (Not Including Serious) Adverse Events
	Salmonella Typhimurium 10 to the 5 th - Level 1		Salmonella Typhimurium 10 to the 6 th - Level 2		Salmonella Typhimurium 10 to the 7 th - Level 3		Salmonella Typhimurium 10 to the 8 th - Level 4		Salmonella Typhimurium 10 to the 9 th - Level 5		Salmonella Typhimurium 10 to the 10 th - Level 6
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/6 (66.7%)		2/3 (66.7%)		3/3 (100%)		3/3 (100%)		2/3 (66.7%)		4/4 (100%)
Blood and lymphatic system disorders
Anemia	0/6 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	2	1/3 (33.3%)	1	1/3 (33.3%)	2	1/4 (25%)	4
Cardiac disorders
Pericardial effusion	0/6 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0
Eye disorders
Eye disorders - Other, specify	0/6 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	1/4 (25%)	1
Gastrointestinal disorders
Abdominal pain	1/6 (16.7%)	1	1/3 (33.3%)	1	1/3 (33.3%)	1	0/3 (0%)	0	2/3 (66.7%)	2	0/4 (0%)	0
Ascites	0/6 (0%)	0	0/3 (0%)	0	2/3 (66.7%)	2	0/3 (0%)	0	0/3 (0%)	0	0/4 (0%)	0
Constipation	2/6 (33.3%)	2	1/3 (33.3%)	1	2/3 (66.7%)	2	2/3 (66.7%)	2	1/3 (33.3%)	1	1/4 (25%)	1
Nausea	2/6 (33.3%)	2	1/3 (33.3%)	1	1/3 (33.3%)	2	0/3 (0%)	0	0/3 (0%)	0	1/4 (25%)	1
Vomiting	1/6 (16.7%)	1	0/3 (0%)	0	1/3 (33.3%)	2	0/3 (0%)	0	0/3 (0%)	0	0/4 (0%)	0
General disorders
Edema limbs	2/6 (33.3%)	2	2/3 (66.7%)	2	3/3 (100%)	3	0/3 (0%)	0	2/3 (66.7%)	2	3/4 (75%)	4
Fatigue	0/6 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0	1/4 (25%)	2
Fever	3/6 (50%)	3	1/3 (33.3%)	1	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	1/4 (25%)	1
Pain	1/6 (16.7%)	1	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	1/3 (33.3%)	1	1/4 (25%)	1
Infections and infestations
Mucosal infection	0/6 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/4 (25%)	2
Investigations
Alanine aminotransferase increased	0/6 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	2/3 (66.7%)	3	0/3 (0%)	0	0/4 (0%)	0
Alkaline phosphatase increased	0/6 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	3	2/3 (66.7%)	2	1/3 (33.3%)	2	1/4 (25%)	1
Aspartate aminotransferase increased	0/6 (0%)	0	0/3 (0%)	0	2/3 (66.7%)	2	2/3 (66.7%)	2	1/3 (33.3%)	1	1/4 (25%)	2
Blood bilirubin increased	0/6 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	2	0/3 (0%)	0	1/4 (25%)	3
Investigations - Other, specify	0/6 (0%)	0	0/3 (0%)	0	2/3 (66.7%)	2	0/3 (0%)	0	0/3 (0%)	0	0/4 (0%)	0
Metabolism and nutrition disorders
Anorexia	2/6 (33.3%)	2	1/3 (33.3%)	1	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/4 (0%)	0
Hyperkalemia	0/6 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	2	0/3 (0%)	0	0/3 (0%)	0	0/4 (0%)	0
Hypoalbuminemia	0/6 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0	1/4 (25%)	1
Hyponatremia	0/6 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	2	0/3 (0%)	0	0/3 (0%)	0	0/4 (0%)	0
Metabolism and nutrition disorders - Other, specify	0/6 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	1	0/3 (0%)	0	0/4 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/6 (0%)	0	2/3 (66.7%)	2	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0
Back pain	1/6 (16.7%)	1	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	1/4 (25%)	1
Generalized muscle weakness	2/6 (33.3%)	2	0/3 (0%)	0	1/3 (33.3%)	2	0/3 (0%)	0	0/3 (0%)	0	0/4 (0%)	0
Muscle weakness lower limb	1/6 (16.7%)	1	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/4 (25%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	0/6 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	1/3 (33.3%)	3	0/3 (0%)	0	0/4 (0%)	0
Nervous system disorders
Headache	0/6 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	2	1/3 (33.3%)	1	0/3 (0%)	0	0/4 (0%)	0
Peripheral sensory neuropathy	1/6 (16.7%)	1	0/3 (0%)	0	0/3 (0%)	0	2/3 (66.7%)	3	2/3 (66.7%)	2	3/4 (75%)	3
Psychiatric disorders
Confusion	1/6 (16.7%)	1	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	2	0/3 (0%)	0	0/4 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/6 (16.7%)	1	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/4 (0%)	0
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, specify	2/6 (33.3%)	3	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	1	0/4 (0%)	0
Vascular disorders
Hypertension	0/6 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	2	0/3 (0%)	0	0/4 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.