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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SB-485232+Rituximab | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SB-485232 | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| safety/tolerability of combination treatment for 4 weeks safety/tolerability of SB-485232 for additional 8 weeks | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| assess blood values of combination treatment for 4 weeks assess blood values of SB-485232 for additional 8 weeks | 12 weeks | |
| Pharmacokinetic parameters for SB-485232 and Rituxan: AUCtau, Cmax, and Cmin. | 12 weeks |
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Inclusion Criteria:
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:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Chicago | Illinois | 60637 | United States | ||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23799412 | Background | 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. |
| Label | URL |
|---|---|
| Results for study ILI105618 can be found on the GSK Clinical Study Register. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| ILI105618 | Study Protocol | View IPD |
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
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| ID | Term |
|---|---|
| D020382 | Interleukin-18 |
| D000069283 | Rituximab |
| ID | Term |
|---|---|
| D007378 | Interleukins |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
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| Rituximab | Drug | Rituximab 375 mg/m^2 will be administered by IV infusion. |
|
| Pharmacodynamic biomarker responses: | 12 weeks |
| Plasma IFN-γ, GMCSF, IP-10, MIG, and MCP-1 changes | from baseline and predose |
| Plasma IL-18BP change | from baseline |
| PBMC phenotype changes | from baseline and pre-dose |
| Activated NK cells (CD16+/CD56+/CD3-/CD69+/FasL+ or IL-18Ra+) | 12 weeks |
| Activated cytolytic T cells (CD8+/CD4-/CD3+/CD69+ FasL+ or IL- 18Ra+) | 12 weeks |
| Activated B cells (CD19+/CD25-/CD3-/CD69+) | 12 weeks |
| Activated Neutrophils/Monocytes (CD11b+/CD16+/CD64+/CD14+/CD45+/CD69+) | 12 weeks |
| Regulatory T-cells (FoxP3+/CD25+/CD4+/CD127+) | 12 weeks |
| Immunogenicity (anti-SB-485232 and anti-Rituximab antibodies) | 12 weeks |
| Anti-tumor activity (Radiographic tumor assessments) | 12 weeks |
| CD16 (FcγRIIIA) 158V/F genotyping | 12 weeks |
| Indianapolis |
| Indiana |
| 46202 |
| United States |
| Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. | View source |
For additional information about this study please refer to the GSK Clinical Study Register |
| ILI105618 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| ILI105618 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| ILI105618 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| ILI105618 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| ILI105618 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| ILI105618 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| D006425 |
| Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D000602 |
| Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |