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

• Sponsor: Academic and Community Cancer Research United (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02758717
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 46
• Locations: 9
• Arm: 1
• Anticipated Duration (Months): 96
• Patients Per Site: 5.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This phase II trial studies how well nivolumab and brentuximab vedotin work in treating older patients with untreated Hodgkin lymphoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Biological therapies, such as brentuximab vedotin, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Nivolumab and brentuximab vedotin may work better in treating older patients with untreated Hodgkin lymphoma.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Brentuximab Vedotin; Biological: Nivolumab	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

1. To determine the efficacy based on overall metabolic response rate (partial metabolic response [PMR] + complete metabolic remission [CMR]) of brentuximab vedotin/nivolumab in previously untreated Hodgkin lymphoma patients 60 years of age or older, or those considered unsuitable for standard chemotherapy because of a low cardiac ejection fraction (< 50%) or impaired pulmonary or renal function.

SECONDARY OBJECTIVES:

1. The complete metabolic response (CMR) rate. II. Safety and tolerability of the regimen in this patient population. III. Duration of response (DOR). IV. Progression-free survival (PFS). V. Overall survival (OS).

CORRELATIVE RESEARCH OBJECTIVES:

1. T-cell/cytokine - peripheral blood specimens will be used to assess T-cell activation and cytokine up regulation as measures of treatment effect.

2. Biomarkers - intratumoral cell populations, genetic variability, serum cytokines and T-cell activation will be evaluated to identify potential biomarkers that correlate with response to therapy.

OUTLINE:

Patients receive brentuximab vedotin intravenously (IV) over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for 7 cycles and 6-8 weeks in cycle 8 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 30 days for 90 days, every 90 days for 2.5 years, and then every 6 months until 5 years from registration.

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II, Multi-Center Trial of Nivolumab and Brentuximab Vedotin in Patients With Untreated Hodgkin Lymphoma Over the Age of 60 Years or Unable to Receive Standard Adriamycin, Bleomycin, Vinblastine, and Dacarbazine (ABVD) Chemotherapy
• Actual Study Start Date: May 13, 2016
• Actual Primary Completion Date: Aug 13, 2019
• Anticipated Study Completion Date: May 13, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (brentuximab vedotin, nivolumab) Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for 7 cycles and 6-8 weeks in cycle 8 in the absence of disease progression or unacceptable toxicity.	Drug: Brentuximab Vedotin; Given IV; Other Names: ADC SGN-35 Adcetris Anti-CD30 Antibody-Drug Conjugate SGN-35 Anti-CD30 Monoclonal Antibody-MMAE SGN-35 Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35 cAC10-vcMMAE SGN-35 ; Biological: Nivolumab; Given IV; Other Names: BMS-936558 MDX-1106 NIVO ONO-4538 Opdivo

Outcome Measures

Primary Outcome Measures

1. Overall Metabolic Response Rate [Up to 8 cycles of treatment (approximately 29 weeks)]

   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.

Secondary Outcome Measures

1. Number of Participants With an Overall Response of Complete Metabolic Response [Up to end of course 8]

   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.

2. Duration of Response (DOR) [Assessed up to 5 years]

   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)

3. Progression-free Survival [assessed up to 5 years]

   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)

4. Overall Survival [Time from registration to death due to any cause, assessed up to 5 years]

   The distribution of overall survival will be estimated using the method of Kaplan-Meier.

5. Number of Participants Experiencing at Least One Adverse Events Graded 3 or Higher Deemed at Least Possibly Related to Treatment [Up to 8 cycles of treatment (approximately 29 weeks)]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Classical Hodgkin lymphoma determined by local hematopathology review

• One of the following:

• Age >= 60 years

• Age < 60 years but unsuitable for standard chemotherapy because of a cardiac ejection fraction of < 50%, a pulmonary diffusion capacity < 80%, or a creatinine clearance >= 30 and < 60 mL/min, or refused standard chemotherapy despite efforts to convince them otherwise

• Requirement for systemic chemotherapy: all stages except IA (not bulky disease), if involved field is considered radiotherapy (RT) curative

• Previously untreated with either chemotherapy, radiation therapy or either brentuximab vedotin or nivolumab, or another check point inhibitor

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

• Absolute neutrophil count (ANC) >= 1500/mm^3, unless secondary to bone marrow involvement; obtained =< 7 days prior to registration

• Leukocytes >= 3,000/mm^3, obtained =< 7 days prior to registration

• Platelet count >= 100,000/mm^3, obtained =< 7 days prior to registration

• Hemoglobin > 9.0 g/dL - unless determined by treating physician to be disease related, obtained =< 7 days prior to registration

• Total bilirubin =< 1.5 x upper limit of normal (ULN), obtained =< 7 days prior to registration

• Aspartate aminotransferase (aspartate transaminase [AST]) =< 2.5 x ULN, obtained =< 7 days prior to registration

• Alanine aminotransferase (alanine transaminase [ALT]) =< 2.5 x ULN, obtained =< 7 days prior to registration

• Creatinine =< 2.0 mg/dL, obtained =< 7 days prior to registration

• Amylase and/or lipase =< 1.5 x ULN, obtained =< 7 days prior to registration

• Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to registration

• Note: women of child-bearing potential (WOCBP) must use appropriate method(s) of contraception; WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug; men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year; men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product; women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)

• Note: during the active monitoring phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up

• Ability to understand and willingness to sign an informed written consent

• Provide blood and tissue samples for mandatory correlative research purposes

Exclusion Criteria:

• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:

• Pregnant women

• Nursing women

• Men or women of childbearing potential who are unwilling to employ adequate contraception

• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

• Active, known or suspected autoimmune disease; note: subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger

• Use of systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications =< 14 days of registration; Note: Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease

• Immunocompromised patients, patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) and currently receiving antiretroviral therapy, patients with a prior history of known or suspected autoimmune disease, active hepatitis B virus surface antigen (HBV sAg+), active hepatitis C (if antibody [Ab]+ then polymerase chain reaction [PCR]+) indicating acute or chronic infection, and/or history of interstitial lung disease

• Allergy to brentuximab vedotin and/or nivolumab

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm

• Have had prior chemotherapy or radiotherapy for Hodgkin lymphoma

• Have received either of the study drugs

• < 60 years who are considered candidates for standard chemotherapy

• = grade 2 peripheral neuropathy

• Other active malignancy =< 2 years prior to registration, unless treated with curative intent; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer

• Active central nervous system (CNS) involvement or leptomeningeal metastases involvement

• Known history of pancreatitis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Cancer Institute Palo Alto	Palo Alto	California	United States	94304
2	MedStar Georgetown University Hospital	Washington	District of Columbia	United States	20007
3	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia	United States	30322
4	Mayo Clinic	Rochester	Minnesota	United States	55905
5	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
6	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
7	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
8	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
9	M D Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• Academic and Community Cancer Research United
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Bruce D Cheson, Academic and Community Cancer Research United

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 29, 2020

More Information

Publications

None provided.

• Responsible Party: Academic and Community Cancer Research United
• ClinicalTrials.gov Identifier: NCT02758717
• Other Study ID Numbers: RU051505I; NCI-2016-00468; RU051505I; P30CA015083
• First Posted: May 2, 2016
• Last Update Posted: Jul 22, 2022
• Last Verified: Jan 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Lymphoma; Hodgkin Disease; Antineoplastic Agents, Immunological; Nivolumab; Brentuximab Vedotin; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoconjugates

Study Results

Participant Flow

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 Participants	46
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	71.5
Sex: Female, Male (Count of Participants)
Female	21 45.7%
Male	25 54.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 4.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 4.3%
White	39 84.8%
More than one race	0 0%
Unknown or Not Reported	3 6.5%
ECOG Performance Status (Count of Participants)
0	14 30.4%
1	26 56.5%
2	6 13%

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.
Measure Participants	46
Number (95% Confidence Interval) [percentage of participants]	60.9 132.4%

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.
Measure Participants	46
Count of Participants [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	Assessed up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

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	assessed up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Overall Survival
Description	The distribution of overall survival will be estimated using the method of Kaplan-Meier.
Time Frame	Time from registration to death due to any cause, assessed up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

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.
Measure Participants	46
Count of Participants [Participants]	30 65.2%

Adverse Events

Time Frame	Up to 8 cycles of treatment (approximately 29 weeks)
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 (%)	# Events
Total	4/46 (8.7%)
Serious Adverse Events
	Treatment (Brentuximab Vedotin, Nivolumab)
	Affected / at Risk (%)	# Events
Total	21/46 (45.7%)
Cardiac disorders
Cardiac arrest	1/46 (2.2%)	1
Cardiac disorders - Other, specify	1/46 (2.2%)	1
Sinus tachycardia	1/46 (2.2%)	1
Gastrointestinal disorders
Abdominal pain	2/46 (4.3%)	3
Colitis	1/46 (2.2%)	1
Diarrhea	1/46 (2.2%)	2
Mucositis oral	1/46 (2.2%)	1
Pancreatitis	1/46 (2.2%)	1
General disorders
Death NOS	1/46 (2.2%)	1
Fatigue	1/46 (2.2%)	1
Fever	4/46 (8.7%)	4
Gen disord and admin site conds-Oth spec	1/46 (2.2%)	1
Non-cardiac chest pain	1/46 (2.2%)	1
Hepatobiliary disorders
Cholecystitis	1/46 (2.2%)	1
Infections and infestations
Infections and infestations - Oth spec	2/46 (4.3%)	2
Lung infection	2/46 (4.3%)	2
Sepsis	1/46 (2.2%)	1
Upper respiratory infection	2/46 (4.3%)	2
Urinary tract infection	1/46 (2.2%)	1
Investigations
Creatinine increased	1/46 (2.2%)	1
Lipase increased	2/46 (4.3%)	2
Platelet count decreased	1/46 (2.2%)	1
Serum amylase increased	2/46 (4.3%)	2
Weight loss	1/46 (2.2%)	1
White blood cell decreased	1/46 (2.2%)	1
Metabolism and nutrition disorders
Hypercalcemia	1/46 (2.2%)	1
Hyperglycemia	1/46 (2.2%)	1
Metabolism, nutrition disord - Oth spec	1/46 (2.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, mal, uncpec - Oth spec	1/46 (2.2%)	1
Nervous system disorders
Syncope	2/46 (4.3%)	2
Psychiatric disorders
Confusion	1/46 (2.2%)	1
Hallucinations	1/46 (2.2%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/46 (4.3%)	2
Pleural effusion	1/46 (2.2%)	1
Resp, thoracic, mediastinal - Oth spec	1/46 (2.2%)	1
Skin and subcutaneous tissue disorders
Rash maculo-papular	2/46 (4.3%)	2
Vascular disorders
Hypotension	1/46 (2.2%)	1
Superior vena cava syndrome	1/46 (2.2%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Brentuximab Vedotin, Nivolumab)
	Affected / at Risk (%)	# Events
Total	46/46 (100%)
Blood and lymphatic system disorders
Anemia	4/46 (8.7%)	6
Cardiac disorders
Atrial fibrillation	1/46 (2.2%)	1
Heart failure	1/46 (2.2%)	1
Endocrine disorders
Adrenal insufficiency	1/46 (2.2%)	1
Hypothyroidism	4/46 (8.7%)	9
Gastrointestinal disorders
Abdominal pain	2/46 (4.3%)	2
Constipation	4/46 (8.7%)	8
Diarrhea	5/46 (10.9%)	5
Dysphagia	1/46 (2.2%)	1
Gastroesophageal reflux disease	1/46 (2.2%)	4
Gastrointestinal disorders - Oth spec	1/46 (2.2%)	1
Mucositis oral	2/46 (4.3%)	5
Nausea	8/46 (17.4%)	10
Rectal fistula	1/46 (2.2%)	2
General disorders
Fatigue	15/46 (32.6%)	34
Fever	2/46 (4.3%)	2
Pain	1/46 (2.2%)	1
Infections and infestations
Infections and infestations - Oth spec	3/46 (6.5%)	4
Papulopustular rash	1/46 (2.2%)	3
Sepsis	1/46 (2.2%)	1
Sinusitis	1/46 (2.2%)	1
Upper respiratory infection	1/46 (2.2%)	1
Urinary tract infection	3/46 (6.5%)	6
Injury, poisoning and procedural complications
Infusion related reaction	5/46 (10.9%)	8
Investigations
Alanine aminotransferase increased	4/46 (8.7%)	9
Aspartate aminotransferase increased	3/46 (6.5%)	8
Creatinine increased	12/46 (26.1%)	35
Ejection fraction decreased	1/46 (2.2%)	1
GGT increased	1/46 (2.2%)	1
INR increased	2/46 (4.3%)	4
Investigations - Other, specify	1/46 (2.2%)	1
Lipase increased	6/46 (13%)	16
Lymphocyte count decreased	5/46 (10.9%)	24
Neutrophil count decreased	19/46 (41.3%)	57
Platelet count decreased	15/46 (32.6%)	61
Serum amylase increased	6/46 (13%)	10
Weight gain	1/46 (2.2%)	2
Weight loss	2/46 (4.3%)	8
White blood cell decreased	24/46 (52.2%)	76
Metabolism and nutrition disorders
Anorexia	2/46 (4.3%)	7
Dehydration	1/46 (2.2%)	1
Glucose intolerance	1/46 (2.2%)	8
Hypercalcemia	1/46 (2.2%)	1
Hyperglycemia	6/46 (13%)	22
Hyperkalemia	1/46 (2.2%)	1
Hypernatremia	1/46 (2.2%)	1
Hyperuricemia	1/46 (2.2%)	1
Hypoalbuminemia	1/46 (2.2%)	1
Hypoglycemia	1/46 (2.2%)	1
Hypokalemia	1/46 (2.2%)	1
Hypomagnesemia	1/46 (2.2%)	1
Hyponatremia	2/46 (4.3%)	2
Hypophosphatemia	1/46 (2.2%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	3/46 (6.5%)	6
Arthritis	1/46 (2.2%)	2
Bone pain	1/46 (2.2%)	4
Generalized muscle weakness	2/46 (4.3%)	6
Musculoskeletal, conn tissue - Oth spec	1/46 (2.2%)	1
Myalgia	4/46 (8.7%)	5
Pain in extremity	1/46 (2.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, mal, uncpec - Oth spec	1/46 (2.2%)	1
Nervous system disorders
Headache	1/46 (2.2%)	1
Memory impairment	1/46 (2.2%)	1
Peripheral motor neuropathy	17/46 (37%)	96
Peripheral sensory neuropathy	12/46 (26.1%)	40
Psychiatric disorders
Confusion	1/46 (2.2%)	1
Insomnia	1/46 (2.2%)	1
Psychosis	1/46 (2.2%)	1
Renal and urinary disorders
Acute kidney injury	1/46 (2.2%)	1
Respiratory, thoracic and mediastinal disorders
Cough	2/46 (4.3%)	2
Dyspnea	16/46 (34.8%)	62
Hoarseness	1/46 (2.2%)	1
Hypoxia	1/46 (2.2%)	1
Pneumonitis	1/46 (2.2%)	1
Pulmonary hypertension	1/46 (2.2%)	1
Sore throat	1/46 (2.2%)	1
Skin and subcutaneous tissue disorders
Alopecia	3/46 (6.5%)	17
Pruritus	2/46 (4.3%)	4
Rash maculo-papular	7/46 (15.2%)	19
Vascular disorders
Hot flashes	1/46 (2.2%)	1
Hypertension	10/46 (21.7%)	33
Hypotension	1/46 (2.2%)	1
Thromboembolic event	1/46 (2.2%)	1

Limitations/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.