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

• ClinicalTrials.gov Identifier: NCT02038946
• Recruitment Status: Completed
• First Posted: January 17, 2014
• Results First Posted: June 12, 2018
• Last Update Posted: January 4, 2022
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lymphoma
• Intervention: Drug: Nivolumab
• Enrollment: 116

Participant Flow

Recruitment Details
Pre-assignment Details	116 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 Title	Arm 1: Nivolumab
Arm/Group Description	Nivolumab 3mg/kg intravenously every 2 weeks until disease progression or discontinuation due to toxicity
Period Title: Overall Study
Started	92
Completed [1]	80
Not Completed	12
Reason Not Completed
Death	5
Withdrawal by Subject	3
Lost to Follow-up	2
Other reasons	2
[1] Completed = Participants continuing in the Follow-up period

Baseline Characteristics

Arm/Group Title		Arm 1: Nivolumab
Arm/Group Description		Nivolumab 3mg/kg intravenously every 2 weeks until disease progression or discontinuation due to toxicity
Overall Number of Baseline Participants		92
Baseline Analysis Population Description		All treated participants
Age, Continuous [1]; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	92 participants
		65.2 (10.50)
		[1] Measure Analysis Population Description: All treated participants
Sex: Female, Male [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	92 participants
	Female	44 47.8%
	Male	48 52.2%
		[1] Measure Analysis Population Description: All treated participants
Ethnicity (NIH/OMB) [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	92 participants
	Hispanic or Latino	5 5.4%
	Not Hispanic or Latino	49 53.3%
	Unknown or Not Reported	38 41.3%
		[1] Measure Analysis Population Description: All treated participants
Race (NIH/OMB) [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	92 participants
	American Indian or Alaska Native	0 0.0%
	Asian	3 3.3%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	1 1.1%
	White	87 94.6%
	More than one race	0 0.0%
	Unknown or Not Reported	1 1.1%
		[1] Measure Analysis Population Description: All treated participants

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR) as Determined by IRRC
Description	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)
Time Frame	From 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 Title	Arm 1: Nivolumab
Arm/Group Description:	Nivolumab 3mg/kg intravenously every 2 weeks until disease progression or discontinuation due to toxicity
Overall Number of Participants Analyzed	92
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	4.3; (1.2 to 10.8)

2. Secondary Outcome

Title	Duration of Response (DOR) Based on IRRC Assessments
Description	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
Time Frame	From 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 Title	Arm 1: Nivolumab
Arm/Group Description:	Nivolumab 3mg/kg intravenously every 2 weeks until disease progression or discontinuation due to toxicity
Overall Number of Participants Analyzed	92
Median (95% Confidence Interval); Unit of Measure: months
	10.94; (8.31 to 13.57)

3. Secondary Outcome

Title	Complete Remission Rate (CRR) Based on IRRC Assessment
Description	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.
Time Frame	From 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 Title	Arm 1: Nivolumab
Arm/Group Description:	Nivolumab 3mg/kg intravenously every 2 weeks until disease progression or discontinuation due to toxicity
Overall Number of Participants Analyzed	92
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	1.1; (0.0 to 5.9)

4. Secondary Outcome

Title	Partial Remission (PR) Rate Based on IRRC Assessment
Description	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)
Time Frame	From 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 Title	Arm 1: Nivolumab
Arm/Group Description:	Nivolumab 3mg/kg intravenously every 2 weeks until disease progression or discontinuation due to toxicity
Overall Number of Participants Analyzed	92
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	3.3; (0.7 to 9.2)

5. Secondary Outcome

Title	Progression Free Survival (PFS) Based on IRRC Assessment
Description	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.
Time Frame	From 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 Title	Arm 1: Nivolumab
Arm/Group Description:	Nivolumab 3mg/kg intravenously every 2 weeks until disease progression or discontinuation due to toxicity
Overall Number of Participants Analyzed	92
Median (95% Confidence Interval); Unit of Measure: months
	2.20; (1.91 to 3.58)

6. Secondary Outcome

Title	Overall Response Rate (ORR) Based on Investigator Assessments
Description	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)
Time Frame	From 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 Title	Arm 1: Nivolumab
Arm/Group Description:	Nivolumab 3mg/kg intravenously every 2 weeks until disease progression or discontinuation due to toxicity
Overall Number of Participants Analyzed	92
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	10.9; (5.3 to 19.1)

Adverse Events

Time Frame	AEs 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	[Not Specified]
Arm/Group Title	Nivolumab 3 mg/kg
Arm/Group Description	Nivolumab 3mg/kg intravenously every 2 weeks until disease progression or discontinuation due to toxicity
All-Cause Mortality
	Nivolumab 3 mg/kg
	Affected / at Risk (%)
Total	36/92 (39.13%)
Serious Adverse Events
	Nivolumab 3 mg/kg
	Affected / at Risk (%)
Total	46/92 (50.00%)
Blood and lymphatic system disorders
Autoimmune haemolytic anaemia † 1	1/92 (1.09%)
Cytopenia † 1	1/92 (1.09%)
Febrile neutropenia † 1	4/92 (4.35%)
Pancytopenia † 1	1/92 (1.09%)
Cardiac disorders
Cardiac failure † 1	1/92 (1.09%)
Cardiac failure acute † 1	1/92 (1.09%)
Cardiac failure congestive † 1	1/92 (1.09%)
Myocardial infarction † 1	1/92 (1.09%)
Gastrointestinal disorders
Abdominal discomfort † 1	1/92 (1.09%)
Abdominal pain † 1	3/92 (3.26%)
Ascites † 1	1/92 (1.09%)
Colitis † 1	1/92 (1.09%)
Constipation † 1	1/92 (1.09%)
Diarrhoea † 1	3/92 (3.26%)
Diverticulum intestinal haemorrhagic † 1	1/92 (1.09%)
Dysphagia † 1	1/92 (1.09%)
Gastrointestinal pain † 1	1/92 (1.09%)
Intestinal obstruction † 1	1/92 (1.09%)
Pancreatitis acute † 1	1/92 (1.09%)
Small intestinal obstruction † 1	1/92 (1.09%)
Vomiting † 1	1/92 (1.09%)
General disorders
Asthenia † 1	1/92 (1.09%)
Fatigue † 1	1/92 (1.09%)
General physical health deterioration † 1	1/92 (1.09%)
Multiple organ dysfunction syndrome † 1	1/92 (1.09%)
Pyrexia † 1	6/92 (6.52%)
Immune system disorders
Anaphylactic shock † 1	1/92 (1.09%)
Hypersensitivity † 1	1/92 (1.09%)
Infections and infestations
Appendicitis † 1	1/92 (1.09%)
Bacteraemia † 1	2/92 (2.17%)
Erysipelas † 1	1/92 (1.09%)
Fungal infection † 1	1/92 (1.09%)
Herpes zoster † 1	2/92 (2.17%)
Lower respiratory tract infection † 1	3/92 (3.26%)
Pneumonia † 1	2/92 (2.17%)
Pulmonary sepsis † 1	1/92 (1.09%)
Pyelonephritis † 1	1/92 (1.09%)
Skin infection † 1	2/92 (2.17%)
Staphylococcal sepsis † 1	1/92 (1.09%)
Urinary tract infection † 1	1/92 (1.09%)
Viral infection † 1	1/92 (1.09%)
Injury, poisoning and procedural complications
Infusion related reaction † 1	1/92 (1.09%)
Investigations
Influenza B virus test positive † 1	1/92 (1.09%)
Transaminases increased † 1	1/92 (1.09%)
Metabolism and nutrition disorders
Dehydration † 1	1/92 (1.09%)
Hypercalcaemia † 1	1/92 (1.09%)
Hyperglycaemia † 1	2/92 (2.17%)
Hypokalaemia † 1	1/92 (1.09%)
Musculoskeletal and connective tissue disorders
Bone pain † 1	1/92 (1.09%)
Muscular weakness † 1	1/92 (1.09%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphoma † 1	1/92 (1.09%)
Malignant neoplasm progression † 1	8/92 (8.70%)
Myelodysplastic syndrome † 1	1/92 (1.09%)
Squamous cell carcinoma † 1	1/92 (1.09%)
Nervous system disorders
Sciatica † 1	1/92 (1.09%)
Syncope † 1	1/92 (1.09%)
Psychiatric disorders
Confusional state † 1	1/92 (1.09%)
Renal and urinary disorders
Acute kidney injury † 1	1/92 (1.09%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	1/92 (1.09%)
Aspiration † 1	1/92 (1.09%)
Dyspnoea † 1	1/92 (1.09%)
Immune-mediated pneumonitis † 1	1/92 (1.09%)
Pleural effusion † 1	2/92 (2.17%)
Pneumonitis † 1	1/92 (1.09%)
Respiratory failure † 1	1/92 (1.09%)
Skin and subcutaneous tissue disorders
Erythema multiforme † 1	1/92 (1.09%)
Rash † 1	1/92 (1.09%)
Toxic epidermal necrolysis † 1	1/92 (1.09%)
1 Term from vocabulary, 23.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Nivolumab 3 mg/kg
	Affected / at Risk (%)
Total	89/92 (96.74%)
Blood and lymphatic system disorders
Anaemia † 1	15/92 (16.30%)
Neutropenia † 1	10/92 (10.87%)
Thrombocytopenia † 1	8/92 (8.70%)
Gastrointestinal disorders
Abdominal pain † 1	15/92 (16.30%)
Constipation † 1	14/92 (15.22%)
Diarrhoea † 1	22/92 (23.91%)
Dysphagia † 1	5/92 (5.43%)
Nausea † 1	23/92 (25.00%)
Vomiting † 1	12/92 (13.04%)
General disorders
Asthenia † 1	9/92 (9.78%)
Fatigue † 1	23/92 (25.00%)
Oedema peripheral † 1	10/92 (10.87%)
Pyrexia † 1	25/92 (27.17%)
Infections and infestations
Nasopharyngitis † 1	8/92 (8.70%)
Pneumonia † 1	6/92 (6.52%)
Upper respiratory tract infection † 1	11/92 (11.96%)
Urinary tract infection † 1	9/92 (9.78%)
Metabolism and nutrition disorders
Decreased appetite † 1	14/92 (15.22%)
Hypokalaemia † 1	6/92 (6.52%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	6/92 (6.52%)
Back pain † 1	11/92 (11.96%)
Muscle spasms † 1	5/92 (5.43%)
Myalgia † 1	6/92 (6.52%)
Nervous system disorders
Dizziness † 1	7/92 (7.61%)
Headache † 1	5/92 (5.43%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	25/92 (27.17%)
Dyspnoea † 1	13/92 (14.13%)
Oropharyngeal pain † 1	5/92 (5.43%)
Skin and subcutaneous tissue disorders
Pruritus † 1	11/92 (11.96%)
Rash † 1	8/92 (8.70%)
Skin lesion † 1	5/92 (5.43%)
1 Term from vocabulary, 23.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Armand P, Janssens A, Gritti G, Radford J, Timmerman J, Pinto A, Mercadal Vilchez S, Johnson P, Cunningham D, Leonard JP, Rodig SJ, Martin-Regueira P, Sumbul A, Samakoglu S, Tang H, Ansell SM. Efficacy and safety results from CheckMate 140, a phase 2 study of nivolumab for relapsed/refractory follicular lymphoma. Blood. 2021 Feb 4;137(5):637-645. doi: 10.1182/blood.2019004753.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02038946
• Other Study ID Numbers: CA209-140; 2013-003645-42 ( EudraCT Number )
• First Submitted: January 15, 2014
• First Posted: January 17, 2014
• Results First Submitted: May 16, 2018
• Results First Posted: June 12, 2018
• Last Update Posted: January 4, 2022