Brief Title
A Phase 1 Study of Mixed Bacteria Vaccine (MBV) in Patients With Tumors Expressing NY-ESO-1 Antigen
Official Title
A Phase 1 Study of Mixed Bacteria Vaccine (MBV) in Patients With Tumors Expressing NY-ESO-1 Antigen.
Brief Summary
This was a phase 1, open-label, multiple dose, single-arm study. The mixed bacteria vaccine
(MBV) was administered at a starting dose of 250 EU (1 µL) and escalated in each subject to a
dose inducing the desired pyrogenic effect, defined as a body temperature of 38°C to 39.5°C.
The primary objective was to determine the safety profile of MBV in subjects with malignant
tumors that expressed the NY-ESO-1 antigen and to identify the dose that induced the desired
pyrogenic effect. Secondary objectives were to evaluate the immunological effects and tumor
response of subjects following vaccination.
Detailed Description
Subjects in Cohort 1 were enrolled to receive MBV subcutaneously at a starting dose of 250 EU
(1 µL; dose level 1) administered twice weekly. In the absence of a dose-limiting toxicity
(DLT), the MBV dose was escalated in each subject to the MBV dose that elicited the desired
pyrogenic effect, or up to the maximum dose of 547,000 EU (dose level 8). Once the desired
pyrogenic effect was observed, subjects received MBV twice weekly for 4 doses at the
pyrogenic dose level.
Subjects in Cohort 2 were enrolled to receive MBV at the pyrogenic dose level (determined to
be 60,800 EU [dose level 6]) twice weekly for 6 weeks. Vaccinations were injected
intralesionally if possible and subcutaneously if intralesional injection was not possible.
If a fever of 39.5°C to 40°C was observed, the subject's dose was reduced to dose level 5
(20,300 EU [81 μL]).
Subjects were observed at the clinic for up to 6 hours following each vaccination, with vital
signs measured hourly. At baseline and throughout the study, subjects were assessed for
NY-ESO-1-specific humoral and cellular immunity, chemistry, hematology, and cytokine analysis
(interleukin [IL]-1, IL-6, interferon [IFN]-γ, and tumor necrosis factor [TNF]-α). Safety was
monitored continuously throughout the study.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Secondary Outcome
Number of Participants With Serum NY-ESO-1-specific Immune Responses
Condition
Melanoma
Intervention
Mixed bacterial vaccine
Study Arms / Comparison Groups
Cohort 1
Description: Subjects received MBV at a starting dose of 250 EU (dose level 1) twice weekly, with intrasubject dose escalations for each subsequent administration in the absence of a DLT until the desired pyrogenic effect was observed. The maximum possible dose to be investigated was 547,000 EU (dose level 8).
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
17
Start Date
May 2007
Completion Date
May 2013
Primary Completion Date
May 2012
Eligibility Criteria
Inclusion Criteria:
1. Histologically confirmed metastatic melanoma, head and neck cancer, transitional cell
carcinoma, sarcoma, gastrointestinal stroma tumor (GIST) or prostate cancer.
2. Tumor expression of NY-ESO-1 by reverse transcriptase and polymerase chain reaction
(RT-PCR) analysis, preferably, or immunohistochemistry.
3. Expected survival of at least 6 months.
4. Karnofsky performance status ≥ 70%.
5. Fully recovered from surgery.
6. Declined, intolerated or completed standard therapy defined as follows for each tumor
entity:
1. Melanoma - resistance or intolerance to dacarbazine.
2. Sarcoma - resistance or intolerance to anthracyclines and to one
platinum-containing chemotherapy regimen, no indication for irradiation.
3. GIST - failure or intolerance of imatinib and sunitinib.
4. Head and neck cancer - no indication for irradiation, resistance or intolerance
to platinum-containing chemotherapy.
5. Transitional cell carcinoma - resistance or intolerance to cisplatin combined
with gemcitabine.
6. Prostate cancer- failure of antihormonal treatment and resistance or intolerance
to docetaxel.
7. Ovarian carcinoma - failure of standard chemotherapy consisting of a platinum
agent combined with a taxane and of an anthracycline.
8. Esophageal cancer - failure of standard chemotherapy consisting of a platinum
agent.
9. Breast cancer- failure or intolerance of standard first-, second- and third-line
chemotherapy consisting of a taxane and anthracycline. No indication or
resistance to standard antihormonal treatment. No indication or resistance to
human epidermal growth factor receptor (HER)-2-neu targeted therapy. No
indication or resistance to irradiation and/or surgery.
7. Within the last 2 weeks prior to study day 1, vital laboratory parameters must have
been within the normal range, except for the following laboratory parameters, which
must have been within the ranges specified:
- Absolute neutrophil count (ANC): ≥ 1,000/mm3
- Platelet count: ≥ 75,000/mm3
- Alanine aminotransferase (ALT): ≤ 5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST): ≤ 5 x ULN
- Total bilirubin: ≤ 2.5 x ULN
- Creatinine: ≤ 2 mg/dL
8. Age ≥ 18 years.
9. Able and willing to give written informed consent.
Exclusion Criteria:
1. Clinically significant heart disease (New York Heart Association Class III or IV).
2. Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding
disorders.
3. Subjects with serious intercurrent illness requiring hospitalization.
4. Known human immunodeficiency virus positivity.
5. Chemotherapy, radiation therapy or immunotherapy within 4 weeks prior to first dose of
study agent (6 weeks for nitrosoureas).
6. Known autoimmune disease (rheumatoid arthritis, systemic lupus erythematosus), as
these conditions might have interfered with the evaluation of the induced immune
response. Subjects with vitiligo or melanoma-associated hypopigmentation were not
excluded.
7. Chronic use of immunosuppressive drugs such as systemic corticosteroids.
8. Other malignancy within 3 years prior to entry into the study, except for treated
non-melanoma skin cancer and cervical carcinoma in situ.
9. Mental impairment that may have compromised the ability to give informed consent and
comply with the requirements of the study.
10. Lack of availability for immunological and clinical follow-up assessments.
11. Participation in any other clinical trial involving another investigational agent
within 4 weeks prior to first dosing of study agent.
12. Pregnancy or breastfeeding.
13. Women of childbearing potential: Refusal or inability to use effective means of
contraception.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Elke Jager, MD, ,
Location Countries
Germany
Location Countries
Germany
Administrative Informations
NCT ID
NCT00623831
Organization ID
LUD2005-003
Secondary IDs
2006-002015-27
Responsible Party
Sponsor
Study Sponsor
Ludwig Institute for Cancer Research
Collaborators
Krankenhaus Nordwest
Study Sponsor
Elke Jager, MD, Principal Investigator, Krankenhaus Nordwest
Verification Date
October 2022