Nivolumab and Brentuximab Vedotin in Treating Older Patients With Untreated Hodgkin Lymphoma

• ClinicalTrials.gov Identifier: NCT02758717
• Recruitment Status: Active, not recruiting
• First Posted: May 2, 2016
• Results First Posted: September 22, 2020
• Last Update Posted: May 6, 2024
• Sponsor: Academic and Community Cancer Research United
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Academic and Community Cancer Research United

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Ann Arbor Stage IB Hodgkin Lymphoma; Ann Arbor Stage II Hodgkin Lymphoma; Ann Arbor Stage IIA Hodgkin Lymphoma; Ann Arbor Stage IIB Hodgkin Lymphoma; Ann Arbor Stage III Hodgkin Lymphoma; Ann Arbor Stage IIIA Hodgkin Lymphoma; Ann Arbor Stage IIIB Hodgkin Lymphoma; Ann Arbor Stage IV Hodgkin Lymphoma; Ann Arbor Stage IVA Hodgkin Lymphoma; Ann Arbor Stage IVB Hodgkin Lymphoma; Classic Hodgkin Lymphoma
• Interventions: Drug: Brentuximab Vedotin; Biological: Nivolumab
• Enrollment: 46

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Treatment (Brentuximab Vedotin, Nivolumab)
Arm/Group Description	Patients receive 1.8 mg/kg (cap at 180 mg) in 100 to 250 mL NS to final concentration 0.4 mg/mL to 1.8 mg/mL brentuximab vedotin IV over 30 minutes and 3 mg/kg in 100 cc NS nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
Started	46
Completed	46
Not Completed	0

Baseline Characteristics

Arm/Group Title		Treatment (Brentuximab Vedotin, Nivolumab)
Arm/Group Description		Patients receive 1.8 mg/kg (cap at 180 mg) in 100 to 250 mL NS to final concentration 0.4 mg/mL to 1.8 mg/mL brentuximab vedotin IV over 30 minutes and 3 mg/kg in 100 cc NS nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Baseline Participants		46
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	46 participants
		71.5; (46.0 to 87)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	46 participants
	Female	21 45.7%
	Male	25 54.3%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	46 participants
	American Indian or Alaska Native	0 0.0%
	Asian	2 4.3%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	2 4.3%
	White	39 84.8%
	More than one race	0 0.0%
	Unknown or Not Reported	3 6.5%
ECOG Performance Status [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	46 participants
	0	14 30.4%
	1	26 56.5%
	2	6 13.0%
		[1] Measure Description: Eastern Cooperative Oncology Group PS Scale: 0)Fully active, able to carry on all pre-disease performance without restriction; 1)Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2)Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; 3)Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4)Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair.

Outcome Measures

1. Primary Outcome

Title	Overall Metabolic Response Rate
Description	The primary endpoint of this trial is the rate (percentage) of overall metabolic response. A metabolic response is defined as a participant who has achieved an objective status of Partial metabolic response (PMR) or Complete metabolic response (CMR) at the end of cycle 8. Response is based on PET/CT based on the revised 2014 Lugano Classification. (PMR: Score 4 (uptake moderately > liver) or 5 (uptake markedly higher than liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size CMR: Score 1 (no uptake above background), 2 (uptake<=mediastinum), or 3 (uptake > mediastinum but <= liver) with or without a residual mass on PET Deauville 5-Point-Scale. The scale ranges from 1 to 5, where 1 is best and 5 is the worst.
Time Frame	Up to 8 cycles of treatment (approximately 29 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Brentuximab Vedotin, Nivolumab)
Arm/Group Description:	Patients receive 1.8 mg/kg (cap at 180 mg) in 100 to 250 mL NS to final concentration 0.4 mg/mL to 1.8 mg/mL brentuximab vedotin IV over 30 minutes and 3 mg/kg in 100 cc NS nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	46
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	60.9; (45.4 to 74.9)

2. Secondary Outcome

Title	Number of Participants With an Overall Response of Complete Metabolic Response
Description	The number of participants with an overall response of Complete metabolic response. Response is based on PET/CT based on the revised 2014 Lugano Classification. (CMR: Score 1 (no uptake above background), 2 (uptake<=mediastinum), or 3 (uptake > mediastinum but <= liver) with or without a residual mass on PET Deauville 5-Point-Scale. The scale ranges from 1 to 5, where 1 is best and 5 is the worst.
Time Frame	Up to end of course 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Brentuximab Vedotin, Nivolumab)
Arm/Group Description:	Patients receive 1.8 mg/kg (cap at 180 mg) in 100 to 250 mL NS to final concentration 0.4 mg/mL to 1.8 mg/mL brentuximab vedotin IV over 30 minutes and 3 mg/kg in 100 cc NS nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	46
Measure Type: Count of Participants; Unit of Measure: Participants
	22 47.8%

3. Secondary Outcome

Title	Duration of Response (DOR)
Description	DOR is time from the date at which the patient's objective status is first noted to be a CMR or PMR to the earliest date progression (progressive metabolic disease [PMD] or progressive disease [PD]) is documented. Response is based on PET/CT based on the revised 2014 Lugano Classification. (PMR: Score 4 (uptake moderately > liver) or 5 (uptake markedly higher than liver and/or new lesions) CMR: Score 1 (no uptake above background), 2 (uptake<=mediastinum), or 3 (uptake > mediastinum but <= liver) with or without a residual mass on PET Deauville 5-Point-Scale. The scale ranges from 1 to 5, where 1 is best and 5 is the worst. PMD: Score 4 or 5 with an increase in intensity of uptake from baseline and/or New FDG-avid foci consistent with lymphoma at interim or end-of-treatment assessment PD: An individual node/lesion must be abnormal with: LDi > 1.5 cm and Increase by ≥ 50% from PPD nadir and, An increase in LDi or SDi from nadir, 0.5 cm for lesions ≤2 cm, 1.0 cm for lesions > 2 cm)
Time Frame	30 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Brentuximab Vedotin, Nivolumab)
Arm/Group Description:	Patients receive 1.8 mg/kg (cap at 180 mg) in 100 to 250 mL NS to final concentration 0.4 mg/mL to 1.8 mg/mL brentuximab vedotin IV over 30 minutes and 3 mg/kg in 100 cc NS nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	46
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (11.1 to NA)

[1]

Median and upper limit duration of response were not estimatable due to a lack of events. Insufficient number of participants with events

4. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival is defined as the time from registration to the earliest date of documentation of disease progression (Progressive metabolic disease (PMD) or Progressive disease (PD)) or death due to any cause. Response is based on PET/CT based on the revised 2014 Lugano Classification. (PMD: Score 4 or 5 with an increase in intensity of uptake from baseline and/or New FDG-avid foci consistent with lymphoma at interim or end-of-treatment assessment PD: An individual node/lesion must be abnormal with: LDi > 1.5 cm and Increase by ≥ 50% from PPD nadir and, An increase in LDi or SDi from nadir, 0.5 cm for lesions ≤2 cm, 1.0 cm for lesions > 2 cm)
Time Frame	30 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Brentuximab Vedotin, Nivolumab)
Arm/Group Description:	Patients receive 1.8 mg/kg (cap at 180 mg) in 100 to 250 mL NS to final concentration 0.4 mg/mL to 1.8 mg/mL brentuximab vedotin IV over 30 minutes and 3 mg/kg in 100 cc NS nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	46
Median (95% Confidence Interval); Unit of Measure: months
	18.3 [1]; (12.7 to NA)

[1]

The upper limit of the confidence interval was not reached due to a lack of events. Insufficient number of participants with events.

5. Secondary Outcome

Title	Overall Survival
Description	The distribution of overall survival will be estimated using the method of Kaplan-Meier.
Time Frame	30 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Brentuximab Vedotin, Nivolumab)
Arm/Group Description:	Patients receive 1.8 mg/kg (cap at 180 mg) in 100 to 250 mL NS to final concentration 0.4 mg/mL to 1.8 mg/mL brentuximab vedotin IV over 30 minutes and 3 mg/kg in 100 cc NS nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	46
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (NA to NA)

[1]

Median overall survival time was not estimatable due to the low number of patient deaths

6. Secondary Outcome

Title	Number of Participants Experiencing at Least One Adverse Events Graded 3 or Higher Deemed at Least Possibly Related to Treatment
Description	Number of participants experiencing at least one toxicity. Toxicity is defined as an adverse event graded 3 or higher by Common Terminology Criteria for Adverse Events version 4.0 deemed at least possibly related to treatment.
Time Frame	Up to 8 cycles of treatment (approximately 29 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Brentuximab Vedotin, Nivolumab)
Arm/Group Description:	Patients receive 1.8 mg/kg (cap at 180 mg) in 100 to 250 mL NS to final concentration 0.4 mg/mL to 1.8 mg/mL brentuximab vedotin IV over 30 minutes and 3 mg/kg in 100 cc NS nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	46
Measure Type: Count of Participants; Unit of Measure: Participants
	30 65.2%

Adverse Events

Time Frame	30 months
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Treatment (Brentuximab Vedotin, Nivolumab)
Arm/Group Description	Patients receive 1.8 mg/kg (cap at 180 mg) in 100 to 250 mL NS to final concentration 0.4 mg/mL to 1.8 mg/mL brentuximab vedotin IV over 30 minutes and 3 mg/kg in 100 cc NS nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
All-Cause Mortality
	Treatment (Brentuximab Vedotin, Nivolumab)
	Affected / at Risk (%)
Total	4/46 (8.70%)
Serious Adverse Events
	Treatment (Brentuximab Vedotin, Nivolumab)
	Affected / at Risk (%)	# Events
Total	21/46 (45.65%)
Cardiac disorders
Cardiac arrest † 1	1/46 (2.17%)	1
Cardiac disorders - Other, specify † 1	1/46 (2.17%)	1
Sinus tachycardia † 1	1/46 (2.17%)	1
Gastrointestinal disorders
Abdominal pain † 1	2/46 (4.35%)	3
Colitis † 1	1/46 (2.17%)	1
Diarrhea † 1	1/46 (2.17%)	2
Mucositis oral † 1	1/46 (2.17%)	1
Pancreatitis † 1	1/46 (2.17%)	1
General disorders
Death NOS † 1	1/46 (2.17%)	1
Fatigue † 1	1/46 (2.17%)	1
Fever † 1	4/46 (8.70%)	4
Gen disord and admin site conds-Oth spec † 1	1/46 (2.17%)	1
Non-cardiac chest pain † 1	1/46 (2.17%)	1
Hepatobiliary disorders
Cholecystitis † 1	1/46 (2.17%)	1
Infections and infestations
Infections and infestations - Oth spec † 1	2/46 (4.35%)	2
Lung infection † 1	2/46 (4.35%)	2
Sepsis † 1	1/46 (2.17%)	1
Upper respiratory infection † 1	2/46 (4.35%)	2
Urinary tract infection † 1	1/46 (2.17%)	1
Investigations
Creatinine increased † 1	1/46 (2.17%)	1
Lipase increased † 1	2/46 (4.35%)	2
Platelet count decreased † 1	1/46 (2.17%)	1
Serum amylase increased † 1	2/46 (4.35%)	2
Weight loss † 1	1/46 (2.17%)	1
White blood cell decreased † 1	1/46 (2.17%)	1
Metabolism and nutrition disorders
Hypercalcemia † 1	1/46 (2.17%)	1
Hyperglycemia † 1	1/46 (2.17%)	1
Metabolism, nutrition disord - Oth spec † 1	1/46 (2.17%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, mal, uncpec - Oth spec † 1	1/46 (2.17%)	1
Nervous system disorders
Syncope † 1	2/46 (4.35%)	2
Psychiatric disorders
Confusion † 1	1/46 (2.17%)	1
Hallucinations † 1	1/46 (2.17%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea † 1	2/46 (4.35%)	2
Pleural effusion † 1	1/46 (2.17%)	1
Resp, thoracic, mediastinal - Oth spec † 1	1/46 (2.17%)	1
Skin and subcutaneous tissue disorders
Rash maculo-papular † 1	2/46 (4.35%)	2
Vascular disorders
Hypotension † 1	1/46 (2.17%)	1
Superior vena cava syndrome † 1	1/46 (2.17%)	1
1 Term from vocabulary, MedDRA 12; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Treatment (Brentuximab Vedotin, Nivolumab)
	Affected / at Risk (%)	# Events
Total	46/46 (100.00%)
Blood and lymphatic system disorders
Anemia † 1	4/46 (8.70%)	6
Cardiac disorders
Atrial fibrillation † 1	1/46 (2.17%)	1
Heart failure † 1	1/46 (2.17%)	1
Endocrine disorders
Adrenal insufficiency † 1	1/46 (2.17%)	1
Hypothyroidism † 1	4/46 (8.70%)	9
Gastrointestinal disorders
Abdominal pain † 1	2/46 (4.35%)	2
Constipation † 1	4/46 (8.70%)	8
Diarrhea † 1	5/46 (10.87%)	5
Dysphagia † 1	1/46 (2.17%)	1
Gastroesophageal reflux disease † 1	1/46 (2.17%)	4
Gastrointestinal disorders - Oth spec † 1	1/46 (2.17%)	1
Mucositis oral † 1	2/46 (4.35%)	5
Nausea † 1	8/46 (17.39%)	10
Rectal fistula † 1	1/46 (2.17%)	2
General disorders
Fatigue † 1	15/46 (32.61%)	34
Fever † 1	2/46 (4.35%)	2
Pain † 1	1/46 (2.17%)	1
Infections and infestations
Infections and infestations - Oth spec † 1	3/46 (6.52%)	4
Papulopustular rash † 1	1/46 (2.17%)	3
Sepsis † 1	1/46 (2.17%)	1
Sinusitis † 1	1/46 (2.17%)	1
Upper respiratory infection † 1	1/46 (2.17%)	1
Urinary tract infection † 1	3/46 (6.52%)	6
Injury, poisoning and procedural complications
Infusion related reaction † 1	5/46 (10.87%)	8
Investigations
Alanine aminotransferase increased † 1	4/46 (8.70%)	9
Aspartate aminotransferase increased † 1	3/46 (6.52%)	8
Creatinine increased † 1	12/46 (26.09%)	35
Ejection fraction decreased † 1	1/46 (2.17%)	1
GGT increased † 1	1/46 (2.17%)	1
INR increased † 1	2/46 (4.35%)	4
Investigations - Other, specify † 1	1/46 (2.17%)	1
Lipase increased † 1	6/46 (13.04%)	16
Lymphocyte count decreased † 1	5/46 (10.87%)	24
Neutrophil count decreased † 1	19/46 (41.30%)	57
Platelet count decreased † 1	15/46 (32.61%)	61
Serum amylase increased † 1	6/46 (13.04%)	10
Weight gain † 1	1/46 (2.17%)	2
Weight loss † 1	2/46 (4.35%)	8
White blood cell decreased † 1	24/46 (52.17%)	76
Metabolism and nutrition disorders
Anorexia † 1	2/46 (4.35%)	7
Dehydration † 1	1/46 (2.17%)	1
Glucose intolerance † 1	1/46 (2.17%)	8
Hypercalcemia † 1	1/46 (2.17%)	1
Hyperglycemia † 1	6/46 (13.04%)	22
Hyperkalemia † 1	1/46 (2.17%)	1
Hypernatremia † 1	1/46 (2.17%)	1
Hyperuricemia † 1	1/46 (2.17%)	1
Hypoalbuminemia † 1	1/46 (2.17%)	1
Hypoglycemia † 1	1/46 (2.17%)	1
Hypokalemia † 1	1/46 (2.17%)	1
Hypomagnesemia † 1	1/46 (2.17%)	1
Hyponatremia † 1	2/46 (4.35%)	2
Hypophosphatemia † 1	1/46 (2.17%)	1
Musculoskeletal and connective tissue disorders
Arthralgia † 1	3/46 (6.52%)	6
Arthritis † 1	1/46 (2.17%)	2
Bone pain † 1	1/46 (2.17%)	4
Generalized muscle weakness † 1	2/46 (4.35%)	6
Musculoskeletal, conn tissue - Oth spec † 1	1/46 (2.17%)	1
Myalgia † 1	4/46 (8.70%)	5
Pain in extremity † 1	1/46 (2.17%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, mal, uncpec - Oth spec † 1	1/46 (2.17%)	1
Nervous system disorders
Headache † 1	1/46 (2.17%)	1
Memory impairment † 1	1/46 (2.17%)	1
Peripheral motor neuropathy † 1	17/46 (36.96%)	96
Peripheral sensory neuropathy † 1	12/46 (26.09%)	40
Psychiatric disorders
Confusion † 1	1/46 (2.17%)	1
Insomnia † 1	1/46 (2.17%)	1
Psychosis † 1	1/46 (2.17%)	1
Renal and urinary disorders
Acute kidney injury † 1	1/46 (2.17%)	1
Respiratory, thoracic and mediastinal disorders
Cough † 1	2/46 (4.35%)	2
Dyspnea † 1	16/46 (34.78%)	62
Hoarseness † 1	1/46 (2.17%)	1
Hypoxia † 1	1/46 (2.17%)	1
Pneumonitis † 1	1/46 (2.17%)	1
Pulmonary hypertension † 1	1/46 (2.17%)	1
Sore throat † 1	1/46 (2.17%)	1
Skin and subcutaneous tissue disorders
Alopecia † 1	3/46 (6.52%)	17
Pruritus † 1	2/46 (4.35%)	4
Rash maculo-papular † 1	7/46 (15.22%)	19
Vascular disorders
Hot flashes † 1	1/46 (2.17%)	1
Hypertension † 1	10/46 (21.74%)	33
Hypotension † 1	1/46 (2.17%)	1
Thromboembolic event † 1	1/46 (2.17%)	1
1 Term from vocabulary, MedDRA 12; † 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.

Results Point of Contact

• Name/Title: Bruce D. Cheson, M.D.
• Organization: Lombardi Comprehensive Cancer Center
• Phone: 507-266-0800
• EMail: bdc4@georgetown.edu

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

Cheson BD, Bartlett NL, LaPlant B, Lee HJ, Advani RJ, Christian B, Diefenbach CS, Feldman TA, Ansell SM. Brentuximab vedotin plus nivolumab as first-line therapy in older or chemotherapy-ineligible patients with Hodgkin lymphoma (ACCRU): a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2020 Nov;7(11):e808-e815. doi: 10.1016/S2352-3026(20)30275-1. Epub 2020 Oct 1.

• Responsible Party: Academic and Community Cancer Research United
• ClinicalTrials.gov Identifier: NCT02758717
• Other Study ID Numbers: RU051505I; NCI-2016-00468 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); RU051505I ( Other Identifier: Academic and Community Cancer Research United ); P30CA015083 ( U.S. NIH Grant/Contract )
• First Submitted: April 12, 2016
• First Posted: May 2, 2016
• Results First Submitted: June 24, 2020
• Results First Posted: September 22, 2020
• Last Update Posted: May 6, 2024