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CheckMate 647: A Study of Nivolumab in Relapsed/Refractory Primary Central Nervous System Lymphoma (PCNSL) and Relapsed/Refractory Primary Testicular Lymphoma (PTL)

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT02857426
Collaborator
Ono Pharmaceutical Co. Ltd (Industry)
66
Enrollment
50
Locations
2
Arms
49.1
Actual Duration (Months)
1.3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether Nivolumab is effective in the treatment of Relapsed/Refractory Primary Central Nervous System Lymphoma (PCNSL) and Relapsed/Refractory Primary Testicular Lymphoma (PTL)

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
66 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Open-label, Single-arm, Two-cohort Study of Nivolumab in Relapsed/Refractory Primary Central Nervous System Lymphoma (PCNSL) or Relapsed/Refractory Primary Testicular Lymphoma (PTL)
Actual Study Start Date :
Oct 21, 2016
Actual Primary Completion Date :
Jun 11, 2019
Actual Study Completion Date :
Nov 24, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Nivolumab for population with PCNSL

Specified dose on specified days

Drug: Nivolumab
Other Names:
  • BMS-936558
  • Opdivo

    		•
    Experimental: Nivolumab for population with PTL

    Specified dose on specified days

    Drug: Nivolumab
    Other Names:
  • BMS-936558
  • Opdivo

    		•

    Outcome Measures

    Primary Outcome Measures

    1. BICR-Assessed Objective Response Rate (ORR) [Up to approximately 51 months]

      Percentage of participants with a confirmed objective response rate (ORR) by blinded independent central review (BICR) assessment was analyzed and reported for both PCNSL and PTL patient populations. This endpoint is further defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR), based on the IPCG Criteria for PCNSL and Lugano 2014 response evaluation for PTL, divided by the number of treated participants within each cohort.

    Secondary Outcome Measures

    1. BICR-Assessed Progression Free Survival (PFS) [Up to approximately 51 months]

      Progression-free survival (PFS) is defined as the time from first dosing date to the date of the first documented progression using the IPCG Criteria for PCNSL and Lugano 2014 response evaluation for PTL, as determined by BICR, or death due to any cause, whichever occurs first.

    2. Investigator-Assessed Objective Response Rate (ORR) [Up to approximately 51 months]

      Percentage of participants with a confirmed objective response rate (ORR) by investigator assessment was analyzed and reported for both PCNSL and PTL patient populations. This endpoint is further defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR), based on the IPCG Criteria for PCNSL and Lugano 2014 response evaluation for PTL, divided by the number of treated participants within each cohort.

    3. Investigator-Assessed Duration of Response (DOR) [Up to approximately 51 months]

      Duration of response (DOR) by investigator assessment was analyzed and reported for both PCNSL and PTL patient populations. This endpoint is further defined as the time from first response (CR or PR) to the date of initial objectively documented progression as determined using the IPCG Criteria for PCNSL and Lugano 2014 response evaluation for PTL, as determined by BICR, or death due to any cause, whichever occurs first.

    4. Overall Survival (OS) [Up to approximately 51 months]

      Overall survival (OS) was analyzed and reported for both PCNSL and PTL patient populations. OS is defined as the time from first dosing date to the date of death. For participants without documentation of death, OS will be censored on the last date the participant was known to be alive.

    Eligibility Criteria

    Criteria

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

    For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

    Inclusion Criteria:

    • Pathologically confirmed PCNSL or PTL who failed or did not respond to at least 1 line of systemic therapy

    • Measurable disease requirements on scans:

    PCNSL subjects should have at least one measurable extranodal brain lesion; PTL subjects should have at least 1 measurable extranodal lesion or nodal lesion

    • Have tumor tissue for PD-L1 expression testing

    • Must have a Karnofsky performance status of 70-100

    Exclusion Criteria:
      1. Intraocular PCNSL without evidence of brain disease b) PCNSL patients who cannot undergo MRI assessments c) PCNSL patients with systemic disease

    • Patients with certain diseases such as active autoimmune disease, type I diabetes, hypothyroidism that needs hormone replacement, active infection, psychiatric disorder

    • Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast

    • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways

    PCNSL, and PTL subjects with brain or spinal cord lesion who have received doses of more than 2 mg/day of dexamethasone or equivalent within the 14 days period prior to the first dose of nivolumab are excluded

    Other protocol defined inclusion/exclusion criteria could apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35294-3410
    2 City Of Hope Medical Center Duarte California United States 91010
    3 Mayo Clinic Jacksonville Jacksonville Florida United States 32224
    4 H. Lee Moffitt Cancer Center & Research Inst, Inc Tampa Florida United States 33612
    5 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    6 Massachusetts General Hospital Boston Massachusetts United States 02215
    7 Karmanos Cancer Institute Detroit Michigan United States 48201
    8 Mayo Clinic Rochester Rochester Minnesota United States 55905
    9 Hackensack University Medical Center Hackensack New Jersey United States 07601
    10 Columbia University New York New York United States 10032
    11 Fox Chase Cancer Center Philadelphia Pennsylvania United States 19111
    12 Baylor Research Institute Dallas Texas United States 75246
    13 Swedish Medical Center Seattle Washington United States 98122
    14 Instituto Do Cancer Mae De Deus / Cor Hospital Mae De Deus Porto Alegre Rio Grande Do Sul Brazil 90470-340
    15 Fundacao Pio Xii Hosp Cancer De Barretos Barretos Sao Paulo Brazil 14784-400
    16 Hospital Das Clinicas - Fmusp Sao Paulo Brazil 05403-000
    17 BC Cancer Agency - Vancouver Centre Vancouver British Columbia Canada V5Z 4E6
    18 Princess Margaret Cancer Centre Toronto Ontario Canada M5G 2M9
    19 CHU de Quebec Quebec Canada G1J 1Z4
    20 I. interni klinika - klinika hematologie 1. LF UK a VFN v Praze Praha 2 Czechia 128 08
    21 Local Institution Bordeaux France 33076
    22 Local Institution Caen France 14000
    23 Local Institution La Tronche France 3870
    24 Local Institution Lille Cedex France 59037
    25 Local Institution Paris cedex 13 France 75651
    26 Centre Hospitalier Lyon Sud - UPCO Pierre Benite France 69495
    27 Local Institution Rennes Cedex 9 France 35033
    28 Local Institution St. Cloud France 92210
    29 Local Institution Tours Cedex 9 France 37044
    30 Klinikum Stuttgart Stuttgart Germany 70174
    31 Local Institution Hong Kong Hong Kong
    32 Local Institution Budapest Hungary 1083
    33 Belgyogyaszati Onkologia OOI Budapest Hungary 1122
    34 Local Institution Debrecen Hungary 4032
    35 Local Institution Haifa Israel 3109601
    36 Local Institution Jerusalem Israel 91120
    37 Local Institution Petah Tikva Israel 4941492
    38 Local Institution Tel Aviv Israel 64239
    39 Irccs Ospedale S. Raffaele Milano Italy 20132
    40 Fondazione Policlinico Universitario A. Gemelli Roma Italy 00168
    41 Istituto Clinico Humanitas Rozzano (milano) Italy 20089
    42 Local Institution Nagoya Aichi Japan 4648681
    43 Local Institution Fukuoka-shi Fukuoka Japan 811-1395
    44 Local Institution Hidaka-shi Saitama Japan 3501298
    45 Local Institution Chuo-ku Tokyo Japan 1040045
    46 Local Institution Kotoku Tokyo Japan 1358550
    47 Local Institution Mitaka-shi Tokyo Japan 181-8611
    48 Local Institution Yamagata Japan 9909585
    49 Local Institution Moscow Russian Federation 121309
    50 Local Institution Singapore Singapore 169610

    Sponsors and Collaborators

    • Bristol-Myers Squibb
    • Ono Pharmaceutical Co. Ltd

    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:
    NCT02857426
    Other Study ID Numbers:
    • CA209-647
    • 2016-000894-19
    First Posted:
    Aug 5, 2016
    Last Update Posted:
    Dec 23, 2021
    Last Verified:
    Nov 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Lymphoma
    Nivolumab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 47 PCNSL participants treated. 19 PTL participants treated.
    Arm/Group Title PCNSL Cohort PTL Cohort
    Arm/Group Description Nivolumab dosed to participants with relapsed/refractory Primary Central Nervous System Lymphoma (PCNSL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion. Nivolumab dosed to participants with relapsed/refractory Primary Testicular Lymphoma (PTL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.
    Period Title: Overall Study
    STARTED 47 19
    COMPLETED 0 0
    NOT COMPLETED 47 19

    Baseline Characteristics

    Arm/Group Title PCNSL Cohort PTL Cohort Total
    Arm/Group Description Nivolumab dosed to participants with relapsed/refractory Primary Central Nervous System Lymphoma (PCNSL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion. Nivolumab dosed to participants with relapsed/refractory Primary Testicular Lymphoma (PTL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion. Total of all reporting groups
    Overall Participants 47 19 66
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    65.9
    (10.1)
    66.7
    (8.6)
    66.1
    (9.6)
    Sex: Female, Male (Count of Participants)
    Female
    20
    42.6%
    0
    0%
    20
    30.3%
    Male
    27
    57.4%
    19
    100%
    46
    69.7%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    2.1%
    0
    0%
    1
    1.5%
    Not Hispanic or Latino
    33
    70.2%
    11
    57.9%
    44
    66.7%
    Unknown or Not Reported
    13
    27.7%
    8
    42.1%
    21
    31.8%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    10
    21.3%
    5
    26.3%
    15
    22.7%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    White
    37
    78.7%
    12
    63.2%
    49
    74.2%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    2
    10.5%
    2
    3%

    Outcome Measures

    1. Primary Outcome
    Title BICR-Assessed Objective Response Rate (ORR)
    Description Percentage of participants with a confirmed objective response rate (ORR) by blinded independent central review (BICR) assessment was analyzed and reported for both PCNSL and PTL patient populations. This endpoint is further defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR), based on the IPCG Criteria for PCNSL and Lugano 2014 response evaluation for PTL, divided by the number of treated participants within each cohort.
    Time Frame Up to approximately 51 months

    Outcome Measure Data

    Analysis Population Description
    All treated PCNSL and PTL participants
    Arm/Group Title PCNSL Cohort PTL Cohort
    Arm/Group Description Nivolumab dosed to participants with relapsed/refractory Primary Central Nervous System Lymphoma (PCNSL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion. Nivolumab dosed to participants with relapsed/refractory Primary Testicular Lymphoma (PTL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.
    Measure Participants 47 19
    Number (95% Confidence Interval) [Percentage of participants]
    6.4
    13.6%
    26.3
    138.4%
    2. Secondary Outcome
    Title BICR-Assessed Progression Free Survival (PFS)
    Description Progression-free survival (PFS) is defined as the time from first dosing date to the date of the first documented progression using the IPCG Criteria for PCNSL and Lugano 2014 response evaluation for PTL, as determined by BICR, or death due to any cause, whichever occurs first.
    Time Frame Up to approximately 51 months

    Outcome Measure Data

    Analysis Population Description
    All treated PCNSL and PTL participants
    Arm/Group Title PCNSL Cohort PTL Cohort
    Arm/Group Description Nivolumab dosed to participants with relapsed/refractory Primary Central Nervous System Lymphoma (PCNSL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion. Nivolumab dosed to participants with relapsed/refractory Primary Testicular Lymphoma (PTL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.
    Measure Participants 47 19
    Median (95% Confidence Interval) [Months]
    1.41
    1.72
    3. Secondary Outcome
    Title Investigator-Assessed Objective Response Rate (ORR)
    Description Percentage of participants with a confirmed objective response rate (ORR) by investigator assessment was analyzed and reported for both PCNSL and PTL patient populations. This endpoint is further defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR), based on the IPCG Criteria for PCNSL and Lugano 2014 response evaluation for PTL, divided by the number of treated participants within each cohort.
    Time Frame Up to approximately 51 months

    Outcome Measure Data

    Analysis Population Description
    All treated PCNSL and PTL participants
    Arm/Group Title PCNSL Cohort PTL Cohort
    Arm/Group Description Nivolumab dosed to participants with relapsed/refractory Primary Central Nervous System Lymphoma (PCNSL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion. Nivolumab dosed to participants with relapsed/refractory Primary Testicular Lymphoma (PTL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.
    Measure Participants 47 19
    Number (95% Confidence Interval) [Percentage of participants]
    10.6
    22.6%
    26.3
    138.4%
    4. Secondary Outcome
    Title Investigator-Assessed Duration of Response (DOR)
    Description Duration of response (DOR) by investigator assessment was analyzed and reported for both PCNSL and PTL patient populations. This endpoint is further defined as the time from first response (CR or PR) to the date of initial objectively documented progression as determined using the IPCG Criteria for PCNSL and Lugano 2014 response evaluation for PTL, as determined by BICR, or death due to any cause, whichever occurs first.
    Time Frame Up to approximately 51 months

    Outcome Measure Data

    Analysis Population Description
    All responders PCNSL and PTL participants
    Arm/Group Title PCNSL Cohort PTL Cohort
    Arm/Group Description Nivolumab dosed to participants with relapsed/refractory Primary Central Nervous System Lymphoma (PCNSL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion. Nivolumab dosed to participants with relapsed/refractory Primary Testicular Lymphoma (PTL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.
    Measure Participants 5 5
    Median (95% Confidence Interval) [Months]
    1.71
    20.63
    5. Secondary Outcome
    Title Overall Survival (OS)
    Description Overall survival (OS) was analyzed and reported for both PCNSL and PTL patient populations. OS is defined as the time from first dosing date to the date of death. For participants without documentation of death, OS will be censored on the last date the participant was known to be alive.
    Time Frame Up to approximately 51 months

    Outcome Measure Data

    Analysis Population Description
    All treated PCNSL and PTL participants
    Arm/Group Title PCNSL Cohort PTL Cohort
    Arm/Group Description Nivolumab dosed to participants with relapsed/refractory Primary Central Nervous System Lymphoma (PCNSL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion. Nivolumab dosed to participants with relapsed/refractory Primary Testicular Lymphoma (PTL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.
    Measure Participants 47 19
    Median (95% Confidence Interval) [Months]
    6.77
    11.17

    Adverse Events

    Time Frame From first dose to 100 days post last dose (up to approximately 48 months)
    Adverse Event Reporting Description
    Arm/Group Title PCNSL Cohort Nivolumab 240 mg (Q2W) PTL Cohort Nivolumab 240 mg (Q2W)
    Arm/Group Description Nivolumab dosed to participants with relapsed/refractory Primary Central Nervous System Lymphoma (PCNSL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion. Nivolumab dosed to participants with relapsed/refractory Primary Testicular Lymphoma (PTL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.
    All Cause Mortality
    PCNSL Cohort Nivolumab 240 mg (Q2W) PTL Cohort Nivolumab 240 mg (Q2W)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 32/47 (68.1%) 13/19 (68.4%)
    Serious Adverse Events
    PCNSL Cohort Nivolumab 240 mg (Q2W) PTL Cohort Nivolumab 240 mg (Q2W)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 33/47 (70.2%) 15/19 (78.9%)
    Blood and lymphatic system disorders
    Anaemia 0/47 (0%) 1/19 (5.3%)
    Febrile neutropenia 1/47 (2.1%) 1/19 (5.3%)
    Leukopenia 1/47 (2.1%) 0/19 (0%)
    Pancytopenia 1/47 (2.1%) 0/19 (0%)
    Gastrointestinal disorders
    Dysphagia 1/47 (2.1%) 0/19 (0%)
    General disorders
    Asthenia 1/47 (2.1%) 0/19 (0%)
    Fatigue 1/47 (2.1%) 0/19 (0%)
    Gait disturbance 1/47 (2.1%) 0/19 (0%)
    General physical health deterioration 2/47 (4.3%) 1/19 (5.3%)
    Mucosal inflammation 1/47 (2.1%) 0/19 (0%)
    Pyrexia 1/47 (2.1%) 1/19 (5.3%)
    Sudden death 1/47 (2.1%) 0/19 (0%)
    Hepatobiliary disorders
    Hepatitis 0/47 (0%) 1/19 (5.3%)
    Hepatitis acute 1/47 (2.1%) 0/19 (0%)
    Infections and infestations
    Cystitis 0/47 (0%) 1/19 (5.3%)
    Influenza 1/47 (2.1%) 0/19 (0%)
    Meningitis viral 1/47 (2.1%) 0/19 (0%)
    Pneumonia 0/47 (0%) 1/19 (5.3%)
    Pulmonary sepsis 1/47 (2.1%) 0/19 (0%)
    Sepsis 3/47 (6.4%) 0/19 (0%)
    Septic shock 1/47 (2.1%) 0/19 (0%)
    Urinary tract infection 1/47 (2.1%) 0/19 (0%)
    Vascular device infection 0/47 (0%) 1/19 (5.3%)
    Injury, poisoning and procedural complications
    Cervical vertebral fracture 1/47 (2.1%) 0/19 (0%)
    Fall 2/47 (4.3%) 1/19 (5.3%)
    Hip fracture 1/47 (2.1%) 0/19 (0%)
    Infusion related reaction 1/47 (2.1%) 0/19 (0%)
    Investigations
    Lymphocyte count decreased 1/47 (2.1%) 0/19 (0%)
    Neutrophil count decreased 1/47 (2.1%) 0/19 (0%)
    Platelet count decreased 1/47 (2.1%) 0/19 (0%)
    Metabolism and nutrition disorders
    Dehydration 2/47 (4.3%) 0/19 (0%)
    Failure to thrive 1/47 (2.1%) 0/19 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/47 (0%) 1/19 (5.3%)
    Muscular weakness 1/47 (2.1%) 0/19 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon 0/47 (0%) 1/19 (5.3%)
    Lung adenocarcinoma 0/47 (0%) 1/19 (5.3%)
    Malignant neoplasm progression 13/47 (27.7%) 8/19 (42.1%)
    Tumour flare 2/47 (4.3%) 0/19 (0%)
    Tumour pseudoprogression 1/47 (2.1%) 0/19 (0%)
    Nervous system disorders
    Brain oedema 1/47 (2.1%) 0/19 (0%)
    Cognitive disorder 1/47 (2.1%) 0/19 (0%)
    Depressed level of consciousness 2/47 (4.3%) 0/19 (0%)
    Encephalopathy 2/47 (4.3%) 0/19 (0%)
    Epilepsy 1/47 (2.1%) 0/19 (0%)
    Haemorrhage intracranial 3/47 (6.4%) 0/19 (0%)
    Headache 2/47 (4.3%) 0/19 (0%)
    Hemianopia homonymous 1/47 (2.1%) 0/19 (0%)
    Hemiparesis 1/47 (2.1%) 0/19 (0%)
    Hemiplegia 1/47 (2.1%) 0/19 (0%)
    Mental impairment 1/47 (2.1%) 0/19 (0%)
    Nervous system disorder 1/47 (2.1%) 0/19 (0%)
    Neurological decompensation 2/47 (4.3%) 0/19 (0%)
    Optic neuritis 0/47 (0%) 1/19 (5.3%)
    Seizure 4/47 (8.5%) 1/19 (5.3%)
    Syncope 1/47 (2.1%) 0/19 (0%)
    Psychiatric disorders
    Confusional state 2/47 (4.3%) 0/19 (0%)
    Mental status changes 1/47 (2.1%) 0/19 (0%)
    Renal and urinary disorders
    Acute kidney injury 0/47 (0%) 1/19 (5.3%)
    Renal failure 1/47 (2.1%) 2/19 (10.5%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism 1/47 (2.1%) 0/19 (0%)
    Skin and subcutaneous tissue disorders
    Erythema multiforme 1/47 (2.1%) 0/19 (0%)
    Other (Not Including Serious) Adverse Events
    PCNSL Cohort Nivolumab 240 mg (Q2W) PTL Cohort Nivolumab 240 mg (Q2W)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 40/47 (85.1%) 16/19 (84.2%)
    Blood and lymphatic system disorders
    Anaemia 13/47 (27.7%) 1/19 (5.3%)
    Thrombocytopenia 4/47 (8.5%) 1/19 (5.3%)
    Cardiac disorders
    Bradycardia 2/47 (4.3%) 1/19 (5.3%)
    Tachycardia 0/47 (0%) 1/19 (5.3%)
    Ear and labyrinth disorders
    Tinnitus 1/47 (2.1%) 1/19 (5.3%)
    Vertigo 3/47 (6.4%) 0/19 (0%)
    Eye disorders
    Conjunctival hyperaemia 0/47 (0%) 1/19 (5.3%)
    Dry eye 0/47 (0%) 1/19 (5.3%)
    Eye irritation 1/47 (2.1%) 1/19 (5.3%)
    Glaucoma 0/47 (0%) 2/19 (10.5%)
    Pupils unequal 0/47 (0%) 1/19 (5.3%)
    Vision blurred 1/47 (2.1%) 1/19 (5.3%)
    Gastrointestinal disorders
    Constipation 8/47 (17%) 4/19 (21.1%)
    Diarrhoea 5/47 (10.6%) 2/19 (10.5%)
    Dry mouth 0/47 (0%) 2/19 (10.5%)
    Dysphagia 3/47 (6.4%) 0/19 (0%)
    Haematochezia 0/47 (0%) 1/19 (5.3%)
    Nausea 6/47 (12.8%) 2/19 (10.5%)
    Stomatitis 3/47 (6.4%) 0/19 (0%)
    Vomiting 7/47 (14.9%) 0/19 (0%)
    General disorders
    Asthenia 2/47 (4.3%) 2/19 (10.5%)
    Fatigue 12/47 (25.5%) 2/19 (10.5%)
    Gait disturbance 6/47 (12.8%) 1/19 (5.3%)
    Mucosal inflammation 2/47 (4.3%) 1/19 (5.3%)
    Non-cardiac chest pain 3/47 (6.4%) 1/19 (5.3%)
    Oedema peripheral 3/47 (6.4%) 2/19 (10.5%)
    Pyrexia 9/47 (19.1%) 5/19 (26.3%)
    Hepatobiliary disorders
    Hepatic steatosis 0/47 (0%) 1/19 (5.3%)
    Hepatitis 0/47 (0%) 1/19 (5.3%)
    Hepatotoxicity 0/47 (0%) 1/19 (5.3%)
    Infections and infestations
    Bronchitis 0/47 (0%) 1/19 (5.3%)
    Cellulitis 1/47 (2.1%) 1/19 (5.3%)
    Clostridium difficile infection 1/47 (2.1%) 1/19 (5.3%)
    Gastroenteritis 1/47 (2.1%) 1/19 (5.3%)
    Herpes simplex 0/47 (0%) 1/19 (5.3%)
    Influenza 0/47 (0%) 1/19 (5.3%)
    Oral candidiasis 1/47 (2.1%) 1/19 (5.3%)
    Pneumonia 2/47 (4.3%) 1/19 (5.3%)
    Upper respiratory tract infection 1/47 (2.1%) 1/19 (5.3%)
    Urinary tract infection 5/47 (10.6%) 0/19 (0%)
    Injury, poisoning and procedural complications
    Ankle fracture 0/47 (0%) 1/19 (5.3%)
    Clavicle fracture 0/47 (0%) 1/19 (5.3%)
    Fall 9/47 (19.1%) 3/19 (15.8%)
    Infusion related reaction 2/47 (4.3%) 1/19 (5.3%)
    Procedural pain 0/47 (0%) 1/19 (5.3%)
    Recall phenomenon 0/47 (0%) 1/19 (5.3%)
    Upper limb fracture 0/47 (0%) 1/19 (5.3%)
    Investigations
    Alanine aminotransferase increased 10/47 (21.3%) 1/19 (5.3%)
    Aspartate aminotransferase increased 7/47 (14.9%) 1/19 (5.3%)
    Blood creatinine increased 3/47 (6.4%) 1/19 (5.3%)
    Human rhinovirus test positive 0/47 (0%) 1/19 (5.3%)
    Lipase increased 3/47 (6.4%) 1/19 (5.3%)
    Lymphocyte count decreased 6/47 (12.8%) 0/19 (0%)
    Neutrophil count decreased 5/47 (10.6%) 1/19 (5.3%)
    Platelet count decreased 5/47 (10.6%) 1/19 (5.3%)
    Weight decreased 4/47 (8.5%) 0/19 (0%)
    White blood cell count decreased 3/47 (6.4%) 1/19 (5.3%)
    Metabolism and nutrition disorders
    Decreased appetite 5/47 (10.6%) 0/19 (0%)
    Dehydration 3/47 (6.4%) 0/19 (0%)
    Hyperglycaemia 6/47 (12.8%) 1/19 (5.3%)
    Hypernatraemia 3/47 (6.4%) 1/19 (5.3%)
    Hypoalbuminaemia 5/47 (10.6%) 0/19 (0%)
    Hypocalcaemia 5/47 (10.6%) 0/19 (0%)
    Hypokalaemia 5/47 (10.6%) 1/19 (5.3%)
    Hyponatraemia 7/47 (14.9%) 0/19 (0%)
    Hypophosphataemia 4/47 (8.5%) 0/19 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/47 (4.3%) 4/19 (21.1%)
    Arthritis 1/47 (2.1%) 1/19 (5.3%)
    Back pain 4/47 (8.5%) 0/19 (0%)
    Bursitis 0/47 (0%) 1/19 (5.3%)
    Muscular weakness 4/47 (8.5%) 2/19 (10.5%)
    Musculoskeletal chest pain 1/47 (2.1%) 1/19 (5.3%)
    Myalgia 1/47 (2.1%) 1/19 (5.3%)
    Pain in extremity 3/47 (6.4%) 1/19 (5.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant neoplasm progression 1/47 (2.1%) 1/19 (5.3%)
    Nervous system disorders
    Aphasia 5/47 (10.6%) 0/19 (0%)
    Ataxia 4/47 (8.5%) 0/19 (0%)
    Dizziness 4/47 (8.5%) 0/19 (0%)
    Dysaesthesia 0/47 (0%) 1/19 (5.3%)
    Facial paresis 3/47 (6.4%) 0/19 (0%)
    Headache 12/47 (25.5%) 1/19 (5.3%)
    Hemiparesis 5/47 (10.6%) 0/19 (0%)
    Paraesthesia 3/47 (6.4%) 0/19 (0%)
    Seizure 6/47 (12.8%) 0/19 (0%)
    Somnolence 3/47 (6.4%) 0/19 (0%)
    Psychiatric disorders
    Agitation 3/47 (6.4%) 0/19 (0%)
    Anxiety 4/47 (8.5%) 0/19 (0%)
    Confusional state 4/47 (8.5%) 1/19 (5.3%)
    Depression 3/47 (6.4%) 0/19 (0%)
    Insomnia 5/47 (10.6%) 1/19 (5.3%)
    Renal and urinary disorders
    Acute kidney injury 0/47 (0%) 1/19 (5.3%)
    Chronic kidney disease 1/47 (2.1%) 1/19 (5.3%)
    Urinary incontinence 5/47 (10.6%) 0/19 (0%)
    Reproductive system and breast disorders
    Testicular pain 0/47 (0%) 1/19 (5.3%)
    Testicular swelling 0/47 (0%) 1/19 (5.3%)
    Respiratory, thoracic and mediastinal disorders
    Cough 3/47 (6.4%) 2/19 (10.5%)
    Dyspnoea 3/47 (6.4%) 1/19 (5.3%)
    Pleural effusion 1/47 (2.1%) 1/19 (5.3%)
    Pneumonitis 1/47 (2.1%) 1/19 (5.3%)
    Skin and subcutaneous tissue disorders
    Dermal cyst 0/47 (0%) 1/19 (5.3%)
    Eczema asteatotic 0/47 (0%) 1/19 (5.3%)
    Hyperhidrosis 0/47 (0%) 1/19 (5.3%)
    Pruritus 7/47 (14.9%) 1/19 (5.3%)
    Rash 4/47 (8.5%) 2/19 (10.5%)
    Rash maculo-papular 1/47 (2.1%) 3/19 (15.8%)
    Skin ulcer 0/47 (0%) 1/19 (5.3%)
    Vascular disorders
    Hypotension 0/47 (0%) 1/19 (5.3%)

    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/Title Bristol-Myers Squibb Study Director
    Organization Bristol-Myers Squibb
    Phone Please Email:
    Email Clinical.Trials@bms.com
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT02857426
    Other Study ID Numbers:
    • CA209-647
    • 2016-000894-19
    First Posted:
    Aug 5, 2016
    Last Update Posted:
    Dec 23, 2021
    Last Verified:
    Nov 1, 2021