Last updated: 11/04/2018 08:21:21
A Phase I, Dose-Escalation Study to Assess the Safety and Biological Activity of Recombinant Human Interleukin-18
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A Phase I, Dose-Escalation Study to Assess the Safety and Biological Activity of Recombinant Human Interleukin-18 (SB-485232) Administered by Intravenous Infusion in Combinationwith Rituximab in Adult Patients with B Cell Non-Hodgkin'sLymphoma"
Trial description: The purpose is to identify a dose of SB-485232 which is safe, tolerable and effective when used in combination with Rituximab in patients with non-Hodgkin’s lymphoma (NHL). This study will use a standard treatment regimen of Rituximab in combination with rising doses of SB-485232. The dose selected from this study will be used in a future studies.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:
safety/tolerability of combination treatment for 4 weeks safety/tolerability of SB-485232 for additional 8 weeks
Timeframe: 12 weeks
Secondary outcomes:
assess blood values of combination treatment for 4 weeks assess blood values of SB-485232 for additional 8 weeks
Timeframe: 12 weeks
Pharmacokinetic parameters for SB-485232 and Rituxan: AUCtau, Cmax, and Cmin.
Timeframe: 12 weeks
Pharmacodynamic biomarker responses:
Timeframe: 12 weeks
Plasma IFN-γ, GMCSF, IP-10, MIG, and MCP-1 changes
Timeframe: from baseline and predose
Plasma IL-18BP change
Timeframe: from baseline
PBMC phenotype changes
Timeframe: from baseline and pre-dose
Activated NK cells (CD16+/CD56+/CD3-/CD69+/FasL+ or IL-18Ra+)
Timeframe: 12 weeks
Activated cytolytic T cells (CD8+/CD4-/CD3+/CD69+ FasL+ or IL- 18Ra+)
Timeframe: 12 weeks
Activated B cells (CD19+/CD25-/CD3-/CD69+)
Timeframe: 12 weeks
Activated Neutrophils/Monocytes (CD11b+/CD16+/CD64+/CD14+/CD45+/CD69+)
Timeframe: 12 weeks
Regulatory T-cells (FoxP3+/CD25+/CD4+/CD127+)
Timeframe: 12 weeks
Immunogenicity (anti-SB-485232 and anti-Rituximab antibodies)
Timeframe: 12 weeks
Anti-tumor activity (Radiographic tumor assessments)
Timeframe: 12 weeks
CD16 (FcγRIIIA) 158V/F genotyping
Timeframe: 12 weeks
Interventions:
Enrollment:
24
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Robertson MJ, Kline J, Struemper H, Koch KM, Bauman JW, Gardner OS, Murray SC, Weisenbach J, Jonak Z, Toso JF, Germaschewski F. A dose-escalation study of recombinant human interleukin-18 in combination with rituximab in patients with non-hodgkin's. J Immunother. 2013;36(6):331-341.
Medical condition
Lymphoma, Non-Hodgkin
Product
iboctadekin
Collaborators
Not applicable
Study date(s)
July 2007 to March 2010
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- Histologically confirmed diagnosis of any subtype of CD20+ B cell NHL. Subjects must have disease that progressed after standard therapy or for which there is no effective standard therapy (including high-dose therapy and autologous stem cell transplantation). NOTE: If the subject has had a prior autologous stem cell transplant, it must have occurred at least three months prior to screening and the subject must be fully recovered from any acute toxicities.
- Prior treatment with Rituximab is allowed, provided it was completed at least six months before study enrollment.
- Women who are pregnant or are breast-feeding.
- Significant cardiac, pulmonary, metabolic, renal, hepatic, gastrointestinal or autoimmune conditions that in the opinion of the investigator and/or GSK medical monitor, places the subject at an unacceptable risk as participant in this trial.
Inclusion and exclusion criteria
Inclusion criteria:
- Histologically confirmed diagnosis of any subtype of CD20+ B cell NHL. Subjects must have disease that progressed after standard therapy or for which there is no effective standard therapy (including high-dose therapy and autologous stem cell transplantation). NOTE: If the subject has had a prior autologous stem cell transplant, it must have occurred at least three months prior to screening and the subject must be fully recovered from any acute toxicities.
- Prior treatment with Rituximab is allowed, provided it was completed at least six months before study enrollment.
- Male or female ≥ 18 years of age.
- Measurable or evaluable disease.
- Predicted life expectancy of at least 12 weeks.
- ECOG Performance Status of 0 or 1.
- No chemotherapy, immunotherapy, hormonal therapy, or biological therapy for cancer, radiotherapy, or surgical procedures (except for minor surgical procedures) within four weeks before beginning treatment with SB-485232 (6 weeks for nitrosoureas and mitomycin C). Subjects must have recovered from toxicities (incurred as a result of previous therapy) sufficiently to be entered into a Phase I study.
- A signed and dated written informed consent form is obtained from the subject.
- The subject is able to understand and comply with protocol requirements, timetables, instructions and protocol-stated restrictions. The subject is likely to maintain good venous blood access for PK and PD sampling throughout the study.
- A female is eligible to enter and participate in the study if she is of: a. non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including any female who:
- has had a hysterectomy,
- has had a bilateral oophorectomy (ovariectomy),
- has had a bilateral tubal ligation,
- is post-menopausal (demonstrate total cessation of menses for greater than 1year), If amenorrheic for less than one year, post-menopausal status will be confirmed by serum follicle stimulating hormone (FSH) and oestradiol concentrations at screening. or, b. childbearing potential, has a negative serum pregnancy test at the Screen Visit, and agrees to one of the following GSK acceptable contraceptive methods:
- any intrauterine device (IUD) with a documented failure rate of less than 1% per year.
- vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner for that female.
- oral contraceptive (either combined or progesterone only).
- because of the unacceptable failure rate of barrier (chemical and/or physical) methods, the barrier method of contraception must only be used in combination with other acceptable methods described above.
- Adequate organ function,
Exclusion criteria:
- Women who are pregnant or are breast-feeding.
- Significant cardiac, pulmonary, metabolic, renal, hepatic, gastrointestinal or autoimmune conditions that in the opinion of the investigator and/or GSK medical monitor, places the subject at an unacceptable risk as participant in this trial.
- The subject has diabetes mellitus with poor glycemic control.
- The subject has a history of human immunodeficiency virus (HIV) or other immunodeficiency disease.
- The subject has positive Hepatitis B surface antigen.
- Corrected QT interval (QTc) > 480msec.
- The subject has a history of a severe infusion related reaction or tumor lysis syndrome following treatment with Rituximab (Section 10.2.2).
- The subject has a circulating malignant cell count > 25,000/mm3 in peripheral blood.
- The subject has known anaphylaxis or IgE-mediated hypersensitivity to murine proteins.
- The subject has an acute infection or severe or uncontrolled infections requiring systemic antibiotic therapy.
- Any serious medical or psychiatric disorder that would interfere with subject safety or informed consent.
- Known leptomeningeal disease or evidence of prior or current metastatic brain disease. Routine screening with central nervous system (CNS) imaging studies (CT or MRI) is required only if clinically indicated.
- Receiving concurrent chemotherapy, immunotherapy, radiotherapy, or investigational therapy.
- Oral corticosteroids within 14 days of study entry.
- History of alcohol abuse within six months of screening or alcohol consumption in the past six months exceeding seven drinks/week for women and 14 drinks/week for men (where 1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor).
- History of ventricular arrhythmias requiring drug or device therapy.
- Any unresolved or unstable serious toxicity from prior administration of another investigational drug.
- Any investigational drug within 30 days or five half-lives (whichever is longer) preceding the first dose of SB-485232.
- Donation of blood in excess of 500 mL within a 56-day period prior to dosing.
Trial location(s)
Location
GSK Investigational Site
Indianapolis, Indiana, United States, 46202
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Chicago, Illinois, United States, 60637
Status
Terminated/Withdrawn
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Study complete
Actual primary completion date
Not applicable
Actual study completion date
2010-04-03
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Results for study ILI105618 can be found on the GSK Clinical Study Register.
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