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Lymphoma, Non-HodgkinPhase 1NCT00500058

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

A Phase 1 study testing SB-485232 and Rituximab in people with Lymphoma, Non-Hodgkin, run by GlaxoSmithKline at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma, Non-Hodgkin
What is being tested?
SB-485232 and Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
2 sitesUnited States
Study dates
31 Jul 2007to 4 Mar 2010
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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:
  • 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,

Who cannot join

  • 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.
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  • 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 locations and contacts

2 sites in 1 country.

United States2 sites

  • GSK Investigational Site

    Chicago, Illinois, 60637

  • GSK Investigational Site

    Indianapolis, Indiana, 46202

Other trials in United States

About this study

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"

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.

Being tested
SB-485232, Rituximab
Keywords
Rituximab,, oncology, IL-18,, combination study,, cytokine,
Medical subject headings
Lymphoma, Non-Hodgkin, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SB-485232Drug

    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.

  • RituximabDrug

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

Study groups in NCT00500058
Study groupRoleWhat they receive
SB-485232+RituximabExperimentalRituximab 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.
Receives: Drug: SB-485232; Drug: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 12 weeks

Secondary outcomes (14)

  1. assess blood values of combination treatment for 4 weeks assess blood values of SB-485232 for additional 8 weeks

    Measured: 12 weeks

  2. Pharmacokinetic parameters for SB-485232 and Rituxan: AUCtau, Cmax, and Cmin.

    Measured: 12 weeks

  3. Pharmacodynamic biomarker responses:

    Measured: 12 weeks

  4. Plasma IFN-γ, GMCSF, IP-10, MIG, and MCP-1 changes

    Measured: from baseline and predose

  5. Plasma IL-18BP change

    Measured: from baseline

  6. PBMC phenotype changes

    Measured: from baseline and pre-dose

  7. Activated NK cells (CD16+/CD56+/CD3-/CD69+/FasL+ or IL-18Ra+)

    Measured: 12 weeks

  8. Activated cytolytic T cells (CD8+/CD4-/CD3+/CD69+ FasL+ or IL- 18Ra+)

    Measured: 12 weeks

  9. Activated B cells (CD19+/CD25-/CD3-/CD69+)

    Measured: 12 weeks

  10. Activated Neutrophils/Monocytes (CD11b+/CD16+/CD64+/CD14+/CD45+/CD69+)

    Measured: 12 weeks

  11. Regulatory T-cells (FoxP3+/CD25+/CD4+/CD127+)

    Measured: 12 weeks

  12. Immunogenicity (anti-SB-485232 and anti-Rituximab antibodies)

    Measured: 12 weeks

  13. Anti-tumor activity (Radiographic tumor assessments)

    Measured: 12 weeks

  14. CD16 (FcγRIIIA) 158V/F genotyping

    Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jul 2007 (estimated)
  2. Study start31 Jul 2007
  3. Primary completion4 Mar 2010
  4. Study completion4 Mar 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00500058
Sponsor's protocol ID
ILI105618
Status last verified
Jul 2017
First submitted
10 Jul 2007
Last updated
26 Jul 2017
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Publications

  • 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.

    PubMed 23799412

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing SB-485232 and Rituximab in people with Lymphoma, Non-Hodgkin, run by GlaxoSmithKline at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

safety/tolerability of combination treatment for 4 weeks safety/tolerability of SB-485232 for additional 8 weeks (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00500058, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2017.

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