Study of Nivolumab in Subjects With Relapsed or Refractory Follicular Lymphoma (FL) (CheckMate 140)

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT02038946
Collaborator
(none)
116
Enrollment
45
Locations
1
Arm
81.1
Actual Duration (Months)
2.6
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the clinical benefit of Nivolumab, as measured by independent radiologic review committee (IRRC)-assessed objective response rate (ORR) in subjects with FL lymphoma who have failed therapy with both CD20 antibody and an alkylating agent.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
116 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Single Arm, Open-Label Phase 2 Study of Nivolumab (BMS-936558) in Subjects With Relapsed or Refractory Follicular Lymphoma (FL)
Actual Study Start Date :
Mar 26, 2014
Actual Primary Completion Date :
May 17, 2017
Actual Study Completion Date :
Dec 28, 2020

Arms and Interventions

ArmIntervention/Treatment
Experimental: Arm 1: Nivolumab

Nivolumab 3 mg/kg injection by Intravenous for every 2 weeks until disease progression or discontinuation due to toxicity

Drug: Nivolumab
Other Names:
  • BMS-936558
  • Outcome Measures

    Primary Outcome Measures

    1. Overall Response Rate (ORR) as Determined by IRRC [From Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months)]

      ORR is determined by an independent radiologic review committee (IRRC) according to the revised International Working Group Criteria for non-Hodgkin Lymphoma. ORR is defined as the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) and expressed as a percentage of all treated participants. CR=Disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of spleen, liver, and bone marrow involvement. PR=Regression of measurable disease and no new sites; no increase in size of liver or spleen. >=50% decrease in SPD of up to 6 largest dominant masses (index lesions); no increase in size of other nodes (non-index lesions)

    Secondary Outcome Measures

    1. Duration of Response (DOR) Based on IRRC Assessments [From Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months)]

      DOR is defined as the time from first remission (CR or PR) to the date of initial objectively documented progression as determined using the revised International Working Group Criteria for non-Hodgkin Lymphoma, or death due to any cause, whichever occurs first. CR definition includes the complete disappearance of all evidence of disease, the definition of PR includes at least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses, and PD is defined as any new lesion or increase by >50% of previously involved sites from nadir, as described in the IWG response criteria

    2. Complete Remission Rate (CRR) Based on IRRC Assessment [From Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months)]

      CRR is defined as the number of subjects with a BOR of CR according to the revised International Working Group Criteria for non-Hodgkin Lymphoma, divided by the number of treated participants and expressed as a percentage. CR=Disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of spleen, liver, and bone marrow involvement.

    3. Partial Remission (PR) Rate Based on IRRC Assessment [From Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months)]

      PR rate is defined as the number of participants with a best overall response (BOR) of PR according to the 2007 International Working Group (IWG) criteria, based on IRRC assessment, divided by the number of treated participants and expressed as a percentage. PR=Regression of measurable disease and no new sites; no increase in size of liver or spleen. >=50% decrease in SPD of up to 6 largest dominant masses (index lesions); no increase in size of other nodes (non-index lesions)

    4. Progression Free Survival (PFS) Based on IRRC Assessment [From Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months)]

      PFS was summarized descriptively using the Kaplan-Meier (KM) product-limit method. Median values of PFS, along with the two-sided 95% CIs were calculated using a method based on log-log transformation.

    5. Overall Response Rate (ORR) Based on Investigator Assessments [From Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months)]

      ORR is determined by investigator assessments according to the revised International Working Group Criteria for non-Hodgkin Lymphoma. ORR is defined as the number of subjects with a best overall response (BOR) of complete response (CR) or partial response (PR) and is expressed as a percentage of all treated participants. CR=Disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of spleen, liver, and bone marrow involvement. PR=Regression of measurable disease and no new sites; no increase in size of liver or spleen. >=50% decrease in SPD of up to 6 largest dominant masses (index lesions); no increase in size of other nodes (non-index lesions)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

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

    Inclusion Criteria:
    • Grade 1, 2, or 3a FL without pathologic evidence of transformation

    • Male and female, ages 18 and above, with relapsed or refractory FL lymphoma after > or =2 prior treatment lines; each of the 2 prior treatment lines must include at least CD20 antibody and/or an alkylating agent

    • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1

    Exclusion Criteria:
    • Known central nervous system lymphoma

    • History of interstitial lung disease

    • Subjects with active, known or suspected autoimmune disease

    • Prior allogeneic stem cell transplant

    • Prior autologous stem cell transplant ≤12 weeks prior to first dose of study drug

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Mayo Clinic ArizonaPhoenixArizonaUnited States85054
    2Division Of Hematology & Oncology Ctr. For Health SciencesLos AngelesCaliforniaUnited States90095
    3Winship Cancer Institute.AtlantaGeorgiaUnited States30322
    4Beth Israel Deaconess Medical Center (BIDMC)BostonMassachusettsUnited States02215
    5Dana Farber Cancer InstituteBostonMassachusettsUnited States02215
    6Massachusetts General HospitalBostonMassachusettsUnited States02215
    7Mayo ClinicRochesterMinnesotaUnited States55905
    8Weill Cornell Medical CollegeNew YorkNew YorkUnited States10021
    9Duke University Medical CenterDurhamNorth CarolinaUnited States27710
    10Vanderbilt University Medical CenterNashvilleTennesseeUnited States37232
    11MD Anderson Cancer CenterHoustonTexasUnited States77030
    12Huntsman Cancer InstituteSalt Lake CityUtahUnited States84112
    13Local InstitutionWoodvilleSouth AustraliaAustralia5011
    14Local InstitutionParkvilleVictoriaAustralia3050
    15Local InstitutionB-leuvenBelgium3000
    16Local InstitutionBruxellesBelgium1200
    17Local InstitutionGentBelgium9000
    18Jewish General HospitalMontrealQuebecCanadaH3T 1E2
    19CISSS du Bas-Saint-Laurent Hopital Regional de RimouskiRimouskiQuebecCanadaG5L 5T1
    20Local InstitutionCreteilFrance94010
    21Local InstitutionMontpellier Cedex 05France34295
    22Local InstitutionPierre Benite CedexFrance69495
    23Local InstitutionRennesFrance35033
    24Universitaetsklinikum EssenEssenGermany45147
    25Universitaetsklinikum d. SaarlandesHomburgGermany66424
    26Universitaetsklinikum Des SaarlandesHomburgGermany66424
    27Local InstitutionRegensburgGermany93053
    28Universitaetsklinikum UlmUlmGermany89081
    29Local InstitutionBergamoItaly24127
    30Local InstitutionBolognaItaly40138
    31Local InstitutionMilanoItaly20133
    32Local InstitutionNapoliItaly80131
    33Local InstitutionRomaItaly00161
    34Local InstitutionOsloNorway0424
    35Local InstitutionSingaporeSingapore169865
    36Local InstitutionSingaporeSingapore308433
    37Hospital Duran I ReynalsHospitalet Llobregat- BarcelonaSpain9908
    38Local InstitutionMadridSpain28009
    39Hospital Universitario La PazMadridSpain28046
    40Local InstitutionSalamancaSpain37007
    41Local InstitutionGothenbergSweden413 45
    42Local InstitutionGothenburgSweden413 45
    43Local InstitutionSouthamptonHampshireUnited KingdomSO16 6YD
    44Local InstitutionWithingtonManchesterUnited KingdomM20 4BX
    45Local InstitutionSuttonSurreyUnited KingdomSM2 5PT

    Sponsors and Collaborators

    • Bristol-Myers Squibb

    Investigators

    • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT02038946
    Other Study ID Numbers:
    • CA209-140
    • 2013-003645-42
    First Posted:
    Jan 17, 2014
    Last Update Posted:
    Jan 4, 2022
    Last Verified:
    Dec 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail116 participants were enrolled; 92 received study treatment. Participants were enrolled but not treated because they no longer met study criteria (n=20), withdrew consent (n=1), or for other reasons (n=3).
    Arm/Group TitleArm 1: Nivolumab
    Arm/Group DescriptionNivolumab 3mg/kg intravenously every 2 weeks until disease progression or discontinuation due to toxicity
    Period Title: Overall Study
    STARTED92
    COMPLETED80
    NOT COMPLETED12

    Baseline Characteristics

    Arm/Group TitleArm 1: Nivolumab
    Arm/Group DescriptionNivolumab 3mg/kg intravenously every 2 weeks until disease progression or discontinuation due to toxicity
    Overall Participants92
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    65.2
    (10.50)
    Sex: Female, Male (Count of Participants)
    Female
    44
    47.8%
    Male
    48
    52.2%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    5
    5.4%
    Not Hispanic or Latino
    49
    53.3%
    Unknown or Not Reported
    38
    41.3%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    3
    3.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    1
    1.1%
    White
    87
    94.6%
    More than one race
    0
    0%
    Unknown or Not Reported
    1
    1.1%

    Outcome Measures

    1. Primary Outcome
    TitleOverall Response Rate (ORR) as Determined by IRRC
    DescriptionORR is determined by an independent radiologic review committee (IRRC) according to the revised International Working Group Criteria for non-Hodgkin Lymphoma. ORR is defined as the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) and expressed as a percentage of all treated participants. CR=Disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of spleen, liver, and bone marrow involvement. PR=Regression of measurable disease and no new sites; no increase in size of liver or spleen. >=50% decrease in SPD of up to 6 largest dominant masses (index lesions); no increase in size of other nodes (non-index lesions)
    Time FrameFrom Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months)

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group TitleArm 1: Nivolumab
    Arm/Group DescriptionNivolumab 3mg/kg intravenously every 2 weeks until disease progression or discontinuation due to toxicity
    Measure Participants92
    Number (95% Confidence Interval) [Percentage of participants]
    4.3
    4.7%
    2. Secondary Outcome
    TitleDuration of Response (DOR) Based on IRRC Assessments
    DescriptionDOR is defined as the time from first remission (CR or PR) to the date of initial objectively documented progression as determined using the revised International Working Group Criteria for non-Hodgkin Lymphoma, or death due to any cause, whichever occurs first. CR definition includes the complete disappearance of all evidence of disease, the definition of PR includes at least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses, and PD is defined as any new lesion or increase by >50% of previously involved sites from nadir, as described in the IWG response criteria
    Time FrameFrom Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months)

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group TitleArm 1: Nivolumab
    Arm/Group DescriptionNivolumab 3mg/kg intravenously every 2 weeks until disease progression or discontinuation due to toxicity
    Measure Participants92
    Median (95% Confidence Interval) [months]
    10.94
    3. Secondary Outcome
    TitleComplete Remission Rate (CRR) Based on IRRC Assessment
    DescriptionCRR is defined as the number of subjects with a BOR of CR according to the revised International Working Group Criteria for non-Hodgkin Lymphoma, divided by the number of treated participants and expressed as a percentage. CR=Disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of spleen, liver, and bone marrow involvement.
    Time FrameFrom Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months)

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group TitleArm 1: Nivolumab
    Arm/Group DescriptionNivolumab 3mg/kg intravenously every 2 weeks until disease progression or discontinuation due to toxicity
    Measure Participants92
    Number (95% Confidence Interval) [Percentage of participants]
    1.1
    1.2%
    4. Secondary Outcome
    TitlePartial Remission (PR) Rate Based on IRRC Assessment
    DescriptionPR rate is defined as the number of participants with a best overall response (BOR) of PR according to the 2007 International Working Group (IWG) criteria, based on IRRC assessment, divided by the number of treated participants and expressed as a percentage. PR=Regression of measurable disease and no new sites; no increase in size of liver or spleen. >=50% decrease in SPD of up to 6 largest dominant masses (index lesions); no increase in size of other nodes (non-index lesions)
    Time FrameFrom Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months)

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group TitleArm 1: Nivolumab
    Arm/Group DescriptionNivolumab 3mg/kg intravenously every 2 weeks until disease progression or discontinuation due to toxicity
    Measure Participants92
    Number (95% Confidence Interval) [Percentage of participants]
    3.3
    3.6%
    5. Secondary Outcome
    TitleProgression Free Survival (PFS) Based on IRRC Assessment
    DescriptionPFS was summarized descriptively using the Kaplan-Meier (KM) product-limit method. Median values of PFS, along with the two-sided 95% CIs were calculated using a method based on log-log transformation.
    Time FrameFrom Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months)

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group TitleArm 1: Nivolumab
    Arm/Group DescriptionNivolumab 3mg/kg intravenously every 2 weeks until disease progression or discontinuation due to toxicity
    Measure Participants92
    Median (95% Confidence Interval) [months]
    2.20
    6. Secondary Outcome
    TitleOverall Response Rate (ORR) Based on Investigator Assessments
    DescriptionORR is determined by investigator assessments according to the revised International Working Group Criteria for non-Hodgkin Lymphoma. ORR is defined as the number of subjects with a best overall response (BOR) of complete response (CR) or partial response (PR) and is expressed as a percentage of all treated participants. CR=Disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of spleen, liver, and bone marrow involvement. PR=Regression of measurable disease and no new sites; no increase in size of liver or spleen. >=50% decrease in SPD of up to 6 largest dominant masses (index lesions); no increase in size of other nodes (non-index lesions)
    Time FrameFrom Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months)

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group TitleArm 1: Nivolumab
    Arm/Group DescriptionNivolumab 3mg/kg intravenously every 2 weeks until disease progression or discontinuation due to toxicity
    Measure Participants92
    Number (95% Confidence Interval) [Percentage of participants]
    10.9
    11.8%

    Adverse Events

    Time FrameAEs collected were reported between first dose and 100 days after last dose of study therapy (up to approximately 6 years 9 months)
    Adverse Event Reporting Description
    Arm/Group TitleNivolumab 3 mg/kg
    Arm/Group DescriptionNivolumab 3mg/kg intravenously every 2 weeks until disease progression or discontinuation due to toxicity
    All Cause Mortality
    Nivolumab 3 mg/kg
    Affected / at Risk (%)# Events
    Total36/92 (39.1%)
    Serious Adverse Events
    Nivolumab 3 mg/kg
    Affected / at Risk (%)# Events
    Total46/92 (50%)
    Blood and lymphatic system disorders
    Autoimmune haemolytic anaemia1/92 (1.1%)
    Cytopenia1/92 (1.1%)
    Febrile neutropenia4/92 (4.3%)
    Pancytopenia1/92 (1.1%)
    Cardiac disorders
    Cardiac failure1/92 (1.1%)
    Cardiac failure acute1/92 (1.1%)
    Cardiac failure congestive1/92 (1.1%)
    Myocardial infarction1/92 (1.1%)
    Gastrointestinal disorders
    Abdominal discomfort1/92 (1.1%)
    Abdominal pain3/92 (3.3%)
    Ascites1/92 (1.1%)
    Colitis1/92 (1.1%)
    Constipation1/92 (1.1%)
    Diarrhoea3/92 (3.3%)
    Diverticulum intestinal haemorrhagic1/92 (1.1%)
    Dysphagia1/92 (1.1%)
    Gastrointestinal pain1/92 (1.1%)
    Intestinal obstruction1/92 (1.1%)
    Pancreatitis acute1/92 (1.1%)
    Small intestinal obstruction1/92 (1.1%)
    Vomiting1/92 (1.1%)
    General disorders
    Asthenia1/92 (1.1%)
    Fatigue1/92 (1.1%)
    General physical health deterioration1/92 (1.1%)
    Multiple organ dysfunction syndrome1/92 (1.1%)
    Pyrexia6/92 (6.5%)
    Immune system disorders
    Anaphylactic shock1/92 (1.1%)
    Hypersensitivity1/92 (1.1%)
    Infections and infestations
    Appendicitis1/92 (1.1%)
    Bacteraemia2/92 (2.2%)
    Erysipelas1/92 (1.1%)
    Fungal infection1/92 (1.1%)
    Herpes zoster2/92 (2.2%)
    Lower respiratory tract infection3/92 (3.3%)
    Pneumonia2/92 (2.2%)
    Pulmonary sepsis1/92 (1.1%)
    Pyelonephritis1/92 (1.1%)
    Skin infection2/92 (2.2%)
    Staphylococcal sepsis1/92 (1.1%)
    Urinary tract infection1/92 (1.1%)
    Viral infection1/92 (1.1%)
    Injury, poisoning and procedural complications
    Infusion related reaction1/92 (1.1%)
    Investigations
    Influenza B virus test positive1/92 (1.1%)
    Transaminases increased1/92 (1.1%)
    Metabolism and nutrition disorders
    Dehydration1/92 (1.1%)
    Hypercalcaemia1/92 (1.1%)
    Hyperglycaemia2/92 (2.2%)
    Hypokalaemia1/92 (1.1%)
    Musculoskeletal and connective tissue disorders
    Bone pain1/92 (1.1%)
    Muscular weakness1/92 (1.1%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lymphoma1/92 (1.1%)
    Malignant neoplasm progression8/92 (8.7%)
    Myelodysplastic syndrome1/92 (1.1%)
    Squamous cell carcinoma1/92 (1.1%)
    Nervous system disorders
    Sciatica1/92 (1.1%)
    Syncope1/92 (1.1%)
    Psychiatric disorders
    Confusional state1/92 (1.1%)
    Renal and urinary disorders
    Acute kidney injury1/92 (1.1%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure1/92 (1.1%)
    Aspiration1/92 (1.1%)
    Dyspnoea1/92 (1.1%)
    Immune-mediated pneumonitis1/92 (1.1%)
    Pleural effusion2/92 (2.2%)
    Pneumonitis1/92 (1.1%)
    Respiratory failure1/92 (1.1%)
    Skin and subcutaneous tissue disorders
    Erythema multiforme1/92 (1.1%)
    Rash1/92 (1.1%)
    Toxic epidermal necrolysis1/92 (1.1%)
    Other (Not Including Serious) Adverse Events
    Nivolumab 3 mg/kg
    Affected / at Risk (%)# Events
    Total89/92 (96.7%)
    Blood and lymphatic system disorders
    Anaemia15/92 (16.3%)
    Neutropenia10/92 (10.9%)
    Thrombocytopenia8/92 (8.7%)
    Gastrointestinal disorders
    Abdominal pain15/92 (16.3%)
    Constipation14/92 (15.2%)
    Diarrhoea22/92 (23.9%)
    Dysphagia5/92 (5.4%)
    Nausea23/92 (25%)
    Vomiting12/92 (13%)
    General disorders
    Asthenia9/92 (9.8%)
    Fatigue23/92 (25%)
    Oedema peripheral10/92 (10.9%)
    Pyrexia25/92 (27.2%)
    Infections and infestations
    Nasopharyngitis8/92 (8.7%)
    Pneumonia6/92 (6.5%)
    Upper respiratory tract infection11/92 (12%)
    Urinary tract infection9/92 (9.8%)
    Metabolism and nutrition disorders
    Decreased appetite14/92 (15.2%)
    Hypokalaemia6/92 (6.5%)
    Musculoskeletal and connective tissue disorders
    Arthralgia6/92 (6.5%)
    Back pain11/92 (12%)
    Muscle spasms5/92 (5.4%)
    Myalgia6/92 (6.5%)
    Nervous system disorders
    Dizziness7/92 (7.6%)
    Headache5/92 (5.4%)
    Respiratory, thoracic and mediastinal disorders
    Cough25/92 (27.2%)
    Dyspnoea13/92 (14.1%)
    Oropharyngeal pain5/92 (5.4%)
    Skin and subcutaneous tissue disorders
    Pruritus11/92 (12%)
    Rash8/92 (8.7%)
    Skin lesion5/92 (5.4%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.

    Results Point of Contact

    Name/TitleBristol-Myers Squibb Study Director
    OrganizationBristol-Myers Squibb
    PhonePlease Email
    EmailClinical.Trials@bms.com
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT02038946
    Other Study ID Numbers:
    • CA209-140
    • 2013-003645-42
    First Posted:
    Jan 17, 2014
    Last Update Posted:
    Jan 4, 2022
    Last Verified:
    Dec 1, 2021