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Safety, Tolerability, Pharmacokinetics, and Immunoregulatory Study of Urelumab (BMS-663513) in Subjects With Advanced and/or Metastatic Solid Tumors and Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01471210
First received: November 10, 2011
Last updated: November 20, 2014
Last verified: July 2014

November 10, 2011
November 20, 2014
February 2012
February 2019   (final data collection date for primary outcome measure)
  • Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, physical examinations, and clinical laboratory tests [ Time Frame: Every 3 weeks from Baseline (Day 1) for up to 2 years ] [ Designated as safety issue: Yes ]
    The incidence of adverse events will be tabulated and reviewed for potential significance and clinical Importance.
  • Dose-limiting toxicity and maximum tolerated dose of Urelumab (BMS-663513) as determined by the incidence of dose-limiting toxicities [ Time Frame: Every 3 weeks from Baseline (Day 1) for up to 9 weeks of therapy ] [ Designated as safety issue: Yes ]
  • Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, physical examinations, and clinical laboratory tests [ Time Frame: Once weekly upto 9 weeks of treatment phase ] [ Designated as safety issue: Yes ]
    The incidence of adverse events will be tabulated and reviewed for potential significance and clinical Importance.
  • Dose-limiting toxicity and maximum tolerated dose of BMS-663513 as determined by the incidence of dose-limiting toxicities [ Time Frame: 9 weeks of therapy ] [ Designated as safety issue: Yes ]
  • Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, physical examinations, and clinical laboratory tests [ Time Frame: 60 days after last dose of study therapy ] [ Designated as safety issue: Yes ]
    The incidence of adverse events will be tabulated and reviewed for potential significance and clinical Importance
  • Dose-limiting toxicity and maximum tolerated dose of BMS-663513 as determined by the incidence of dose-limiting toxicities [ Time Frame: Up to 2 years if subject remains on study therapy ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01471210 on ClinicalTrials.gov Archive Site
  • Maximum observed serum concentrations (Cmax) of Urelumab (BMS-663513) [ Time Frame: Cycle 1 Day 1 ] [ Designated as safety issue: No ]
  • Minimum observed serum concentrations (Cmin) of Urelumab (BMS-663513) [ Time Frame: Cycle 2 Day 1, Cycle 3 Day 1, every 12 weeks thereafter up to 2 years ] [ Designated as safety issue: No ]
  • Time of maximum observed serum concentration (Tmax) of Urelumab (BMS-663513) [ Time Frame: Cycle 1 Day 1 ] [ Designated as safety issue: No ]
  • Area under the concentration-time curve in 1 dosing interval [AUC(TAU)] of Urelumab (BMS-663513) [ Time Frame: Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years ] [ Designated as safety issue: No ]
  • Plasma half-life (T-HALF) of Urelumab (BMS-663513) [ Time Frame: Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years ] [ Designated as safety issue: No ]
  • Total body clearance (CLT) of Urelumab (BMS-663513) [ Time Frame: Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years ] [ Designated as safety issue: No ]
  • Volume of distribution at steady-state (Vss) of Urelumab (BMS-663513) [ Time Frame: Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years ] [ Designated as safety issue: No ]
  • Human Anti-human Antibodies [ Time Frame: Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years ] [ Designated as safety issue: No ]
    Immunogenicity of Urelumab (BMS-663513), as determined by blood sample measurements of human antihuman antibodies (HAHA)
  • Tumor response and progression as determined by proportion of patients with best overall response (BOR), progression-free survival (PFS), objective response rate (ORR), time to response, and duration of response [ Time Frame: 9 weeks from Baseline (Day 1) and every 9 weeks until disease progression, death or last tumor assessment (Approximately up to 2 years) ] [ Designated as safety issue: No ]
  • Maximum observed serum concentrations (Cmax) of BMS-663513 [ Time Frame: Cycle 1 Day 1 ] [ Designated as safety issue: No ]
  • Minimum observed serum concentrations (Cmin) of BMS-663513 [ Time Frame: Cycle 2 Day 1, Cycle 3 Day 1, every 12 weeks thereafter up to 2 years ] [ Designated as safety issue: No ]
  • Time of maximum observed serum concentration (Tmax) of BMS-663513 [ Time Frame: Cycle 1 Day 1 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time 0 extrapolated to infinite time [AUC(INF)] of BMS-663513 [ Time Frame: Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years ] [ Designated as safety issue: No ]
  • Area under the concentration-time curve in 1 dosing interval [AUC(TAU)] of BMS-663513 [ Time Frame: Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years ] [ Designated as safety issue: No ]
  • Plasma half-life (T-HALF) of BMS-663513 [ Time Frame: Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years ] [ Designated as safety issue: No ]
  • Total body clearance (CLT) of BMS-663513 [ Time Frame: Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years ] [ Designated as safety issue: No ]
  • Volume of distribution at steady-state (Vss) of BMS-663513 [ Time Frame: Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years ] [ Designated as safety issue: No ]
  • Human Anti-human Antibodies [ Time Frame: Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years ] [ Designated as safety issue: No ]
    Immunogenicity of BMS-663513, as determined by blood sample measurements of human antihuman antibodies (HAHA)
  • Tumor response and progression as determined by proportion of patients with best overall response, progression-free survival, time to response, and duration of response [ Time Frame: Every 9 weeks until disease progression, death or last tumor assessment ] [ Designated as safety issue: No ]
  • Whole Blood RNA expression [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, Cycle 2 Day 1 ] [ Designated as safety issue: No ]
  • Peripheral blood mononuclear cell (PBMC) Flow cytometry data [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, Cycle 2 Day 1, Cycle 2 Day 8 ] [ Designated as safety issue: No ]
  • Serum Cytokines level [ Time Frame: Cycle 1 Day 1 - Day 4, Cycle 2 Day 1, Cycle 2 Day 8 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Safety, Tolerability, Pharmacokinetics, and Immunoregulatory Study of Urelumab (BMS-663513) in Subjects With Advanced and/or Metastatic Solid Tumors and Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma
A Phase 1 Study of the Safety, Tolerability, Pharmacokinetics and Immunoregulatory Activity of Urelumab (BMS-663513) in Subjects With Advanced and/or Metastatic Solid Tumors and Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma (B-NHL)

The purpose of the study is to assess the safety, tolerability, pharmacokinetics and immunoregulatory activity of urelumab (BMS-663513) in cancer subjects with advanced and/or metastatic tumors and relapsed/refractory B-Cell Non-Hodgkin's Lymphoma

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Cancer - Solid Tumors and B-Cell Non-Hodgkin's Lymphoma
Drug: Urelumab (BMS-663513)
  • Experimental: Part 1 : Urelumab (BMS-663513) Dose escalation
    Urelumab (BMS-663513) solution administered intravenously on specified days
    Intervention: Drug: Urelumab (BMS-663513)
  • Experimental: Part 2 : Urelumab (BMS-663513) Cohort Expansion
    Urelumab (BMS-663513) solution administered intravenously on specified days
    Intervention: Drug: Urelumab (BMS-663513)
  • Experimental: Part 3:Urelumab (BMS-663513) Tumor-specific Cohort Expansions
    Enrollment of subjects of three specific tumor types [(colorectal cancer (CRC), head and neck squamous cell carcinoma (SCCHN), and B-Cell non-Hodgkin's lymphoma (B-NHL)] who will be treated at the Maximum Tolerated Dose (MTD) (or highest dose tested)
    Intervention: Drug: Urelumab (BMS-663513)
  • Experimental: Part 4:Urelumab (BMS-663513) Cohort Expansion in B-NHL
    Arm A and Arm B: Urelumab (BMS-663513) liquid administered intravenously on specified days exploring q3w and q6w dosing regimen
    Intervention: Drug: Urelumab (BMS-663513)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
122
March 2019
February 2019   (final data collection date for primary outcome measure)

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

  1. Signed Written Informed Consent

    • The signed informed consent form
  2. Target Population

    • Subjects with advanced and/or metastatic solid tumors or B-NHL who are either refractory to or have relapsed from standard therapies, or for whom a standard therapy does not exist with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
    • Life expectancy of 12 weeks or greater
    • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
    • Adequate organ and marrow function
    • For certain subjects, willing and able to provide pre- and post-treatment fresh tumor biopsies
  3. Age and Reproductive Status

    • Women of childbearing potential (WOCBP) and men must be using an acceptable method of contraception to avoid pregnancy throughout the study and for at least 4 weeks prior to initiation of dosing, and for at least 60 days after the last dose of investigational product in such a manner that the risk of pregnancy is minimized
    • WOCBP must have a negative serum or urine pregnancy test [minimum sensitivity 25 UI/L or equivalent units of human chorionic gonadotrophin (HCG)] within 24 hours prior to the start of investigational product
    • Women must not be breastfeeding

Exclusion Criteria:

  1. Target Disease Exceptions

    • Subjects with known or suspected brain metastasis unless previously treated and without evidence of progression
    • Subjects with a history of prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured
    • Subjects with hepatocellular carcinoma
  2. Medical History and Concurrent Diseases

    • Any active autoimmune disease or documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo, psoriasis inactive within past 2 years, resolved childhood asthma/atopy, or thyroid disease controlled by replacement therapy without the need for immunosuppression
    • Known or suspected human immunodeficiency virus (HIV) or hepatitis A(acute), B or C infection
    • History of any hepatitis (e.g., alcohol or non-alcohol steatohepatitis (NASH), drug-related, auto-immune)
    • Evidence of active infection, requiring parenteral anti-bacterial, anti-viral or anti-fungal therapy < 7 days prior to administration of study medication
    • History of clinically significant cardiac disease, including but not limited to a history (personal or family) of congenital long QT syndrome
    • Grade > 1 QTc prolongation at baseline (> 450 msec by Bazett formula) confirmed by a repeat electrocardiogram (ECG)
    • History of myocardial infarction or uncontrolled angina within 12 months prior to administration of study drug
  3. Physical and Laboratory Test Findings

    • WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 12 weeks after the last dose of investigational product
    • Women who are pregnant or breastfeeding
    • Women with a positive pregnancy test on enrollment or prior to investigational product administration
    • Sexually active fertile men not using effective birth control if their partners are WOCBP
    • Positive blood screen for hepatitis A IgM, hepatitis C antibody, hepatitis B surface antigen, or HIV-1, -2 antibody
  4. Allergies and Adverse Drug Reaction

    • History of allergy to Urelumab (BMS-663513) or related compounds
    • History of significant drug allergy (such as anaphylaxis or hepatotoxicity) to a prior biologic therapy
  5. Prohibited Treatments and/or Therapies

    • The systemic use of the following therapies are prohibited within 28 days of first dose of study medication, or longer where indicated:

      1. Use of anti-cancer treatment (including investigational drugs) within 28 days
      2. Immunosuppressive medications or immunosuppressive doses of systemic corticosteroids
      3. Surgery (except minor surgeries,e.g., biopsies) or radiotherapy
      4. Any non-oncology live viral vaccine therapies used for the prevention of infectious diseases.
    • Prior treatment with anti-programmed death 1 (anti-PD-1)/Programmed cell death 1 ligand 1 (PD-L1) or anti-CD137
    • Any subject with the following reported drug-related adverse events on anti- Cytotoxic T-Lymphocyte Antigen 4 (anti-CTLA4) will not be permitted on study: hepatic, diarrhea/colitis or endocrine adverse events (AE)s Grade ≥ 2, any other non-laboratory immune-related AE ≥ Grade 3. Subjects must have minimum 9 week washout period between the last dose of anti-CTLA4 and the first dose Urelumab (BMS-663513)
    • Prior organ allograft or allogeneic bone marrow transplantation
  6. Other Exclusion Criteria

    • Prisoners or subjects who are involuntarily incarcerated
Both
18 Years and older
No
Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT# and Site #.
United States,   France,   Spain,   United Kingdom
 
NCT01471210
CA186-011, 2012-000170-28
No
Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
July 2014

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