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A Phase I, Dose-Escalation Study to Assess the Safety and Biological Activity of Recombinant Human Interleukin-18

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00500058
First Posted: July 12, 2007
Last Update Posted: July 26, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
July 10, 2007
July 12, 2007
July 26, 2017
July 31, 2007
March 4, 2010   (Final data collection date for primary outcome measure)
safety/tolerability of combination treatment for 4 weeks safety/tolerability of SB-485232 for additional 8 weeks [ Time Frame: 12 weeks ]
  • safety/tolerability of combination treatment for 4 weeks [ Time Frame: for 4 weeks ]
  • Safety/tolerability of SB-485232 for additional 8 weeks [ Time Frame: for additional 8 weeks ]
Complete list of historical versions of study NCT00500058 on ClinicalTrials.gov Archive Site
  • assess blood values of combination treatment for 4 weeks assess blood values of SB-485232 for additional 8 weeks [ Time Frame: 12 weeks ]
  • Pharmacokinetic parameters for SB-485232 and Rituxan: AUCtau, Cmax, and Cmin. [ Time Frame: 12 weeks ]
  • Pharmacodynamic biomarker responses: [ Time Frame: 12 weeks ]
  • Plasma IFN-γ, GMCSF, IP-10, MIG, and MCP-1 changes [ Time Frame: from baseline and predose ]
  • Plasma IL-18BP change [ Time Frame: from baseline ]
  • PBMC phenotype changes [ Time Frame: from baseline and pre-dose ]
  • Activated NK cells (CD16+/CD56+/CD3-/CD69+/FasL+ or IL-18Ra+) [ Time Frame: 12 weeks ]
  • Activated cytolytic T cells (CD8+/CD4-/CD3+/CD69+ FasL+ or IL- 18Ra+) [ Time Frame: 12 weeks ]
  • Activated B cells (CD19+/CD25-/CD3-/CD69+) [ Time Frame: 12 weeks ]
  • Activated Neutrophils/Monocytes (CD11b+/CD16+/CD64+/CD14+/CD45+/CD69+) [ Time Frame: 12 weeks ]
  • Regulatory T-cells (FoxP3+/CD25+/CD4+/CD127+) [ Time Frame: 12 weeks ]
  • Immunogenicity (anti-SB-485232 and anti-Rituximab antibodies) [ Time Frame: 12 weeks ]
  • Anti-tumor activity (Radiographic tumor assessments) [ Time Frame: 12 weeks ]
  • CD16 (FcγRIIIA) 158V/F genotyping [ Time Frame: 12 weeks ]
  • assess blood values of combination treatment for 4 weeks [ Time Frame: for 4 weeks ]
  • assess blood values of SB-485232 for additional 8 weeks [ Time Frame: for additional 8 weeks ]
Not Provided
Not Provided
 
A Phase I, Dose-Escalation Study to Assess the Safety and Biological Activity of Recombinant Human Interleukin-18
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"
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.
Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Lymphoma, Non-Hodgkin
  • Drug: SB-485232
    SB-485232 for injection, 7 mg/vial, will be available as a lyophilized cake. It will be reconstituted with 1.4 mL of water for injection. Each vial of this drug product is a clear, colorless solution containing 5 mg/mL of SB-485232.
  • Drug: Rituximab
    Rituximab 375 mg/m^2 will be administered by IV infusion.
Experimental: SB-485232+Rituximab
Rituximab 375 milligrams per square meter (mg/m^2) will be administered to subjects with CD20+ B cell lymphoma by intravenous (IV) infusion once a week for four consecutive weeks on Day 1 of Weeks 1 to 4. SB-485232 will be administered by IV infusion over a 2 hour period, at doses ranging from 1 microgram (μg)/kilogram (kg) to 100 μg/kg. SB-485232 will be given once a week for 12 consecutive weeks on Day 2 of Weeks 1 to 4 and Day 2 (± 1 day) of Weeks 5 to 12. SB-485232 will be infused at least 24 hours after the Rituximab infusion was started.
Interventions:
  • Drug: SB-485232
  • Drug: Rituximab
Robertson MJ, Kline J, Struemper H, Koch KM, Bauman JW, Gardner OS, Murray SC, Germaschewski F, Weisenbach J, Jonak Z, Toso JF. A dose-escalation study of recombinant human interleukin-18 in combination with rituximab in patients with non-Hodgkin lymphoma. J Immunother. 2013 Jul-Aug;36(6):331-41. doi: 10.1097/CJI.0b013e31829d7e2e.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
March 4, 2010
March 4, 2010   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00500058
ILI105618
No
Not Provided
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
URL: http://
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP