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

NCT00500058 | Completed Phase 1

• 1 other identifier: ILI105618
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Lymphoma, Non-Hodgkin

Keywords

Rituximab,; oncology; IL-18,; combination study,; cytokine,

Outcome Measures

Primary Outcomes (1)

• safety/tolerability of combination treatment for 4 weeks safety/tolerability of SB-485232 for additional 8 weeks

  12 weeks

Secondary Outcomes (14)

• 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

• 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

Study Arms (1)

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.

Drug: SB-485232; Drug: Rituximab

Interventions

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.

SB-485232+Rituximab

Rituximab DRUG

Rituximab 375 mg/m\^2 will be administered by IV infusion.

SB-485232+Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,

You may not qualify if:

• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Chicago, Illinois, 60637, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46202, United States

Location

Related Publications (1)

• 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.

  PMID: 23799412 BACKGROUND

Related Links

• Results for study ILI105618 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Neoplasms

Interventions

Interleukin-18; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2007
• First Posted: July 12, 2007
• Study Start: July 31, 2007
• Primary Completion: March 4, 2010
• Study Completion: March 4, 2010
• Last Updated: July 26, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share

Locations

US (2)