NCT01716806

A Study of Brentuximab Vedotin With Hodgkin Lymphoma (HL) and CD30-expressing Peripheral T-cell Lymphoma (PTCL)

Completed Phase 2 Results posted Last updated 11 June 2024

What this trial tests

Phase 2 trial testing brentuximab vedotin in Hodgkin Disease in 131 participants. Completed in 12 September 2023.

Timeline

31 October 2012

Primary endpoint
7 April 2023

12 September 2023

Quick facts

Lead sponsor	Seagen Inc.
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	131
Start date	31 October 2012
Primary completion	7 April 2023
Estimated completion	12 September 2023
Sites	54 locations across Canada, United States

Drugs / interventions tested

• brentuximab vedotin
• bendamustine (BENDAMUSTINE) — full drug profile →
• dacarbazine (dacarbazine) — full drug profile →
• nivolumab (nivolumab) — full drug profile →

Conditions studied

• Hodgkin Disease — all drugs for Hodgkin Disease →
• Peripheral T Cell Lymphoma — all drugs for Peripheral T Cell Lymphoma →

Sponsor

Seagen Inc. — full company profile →

Who can join

18 and older, any sex, with Hodgkin Disease or Peripheral T Cell Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response Rate (ORR) According to the Revised Response Criteria for Malignant Lymphoma (Parts A, B, and C) Primary · Up to 81 months

Objective response rate (ORR) per investigator was defined as the percentage of subjects with complete response (CR) or partial response (PR) through the end of study or prior to the start of new anti-cancer treatment (including stem cell transplant, and excluding consolidative radiotherapy) other than the study treatment. For Parts A, B, and C the response was assessed using the Revised Response Criteria for Malignant Lymphoma (Cheson 2007).

Group	Value	95% CI
Part A	93	75.7 – 99.1
Part B	95	77.2 – 99.9
Part C	85	62.1 – 96.8

ORR According to the Lugano Classification Revised Staging System for Nodal Non-Hodgkin and Hodgkin Lymphomas (Lugano Criteria) and the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) (Part D) Primary · Up to 60 months

Objective response rate (ORR) per investigator was defined as the percentage of subjects with CR or PR through the end of study or prior to the start of new anti-cancer treatment (including stem cell transplant, and excluding consolidative radiotherapy) other than the study treatment. For Part D, the response was assessed using the Lugano Classification Revised Staging System for nodal non-Hodgkin and cHL (Lugano criteria) and the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC).

Group	Value	95% CI
Part D	86	63.7 – 97.0

ORR According to Modified Lugano Criteria Per Blinded Independent Central Review (BICR) (Parts E and F) Primary · Up to 31 months

Objective response rate (ORR) per investigator was defined as the percentage of subjects with CR or PR through the end of study or prior to the start of new anti-cancer treatment (including stem cell transplant, and excluding consolidative radiotherapy) other than the study treatment. For Parts E and F, the response was assessed per blinded independent central review (BICR) using the modified Lugano criteria.

Group	Value	95% CI
Part E	60	40.6 – 77.3
Part F	43	9.9 – 81.6

Number of Participants With Adverse Events Secondary · Up to 122 months

A treatment-emergent AE (TEAE) is defined as a newly occurring or worsening AE after the first dose of any study drug component. Treatment-related AEs are defined as treatment-emergent AEs that are determined by the investigator to be related to the treatment on study. TEAEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.03). The CTCAE displays Grades 1 through 5, where Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe or medically significant but not immediately life-threatening, Grade 4: Life-threatening consequenc

Any TEAE

Group	Value	95% CI
Part A	27
Part B	22
Part C	20
Part D	21
Part E	30
Part F	7

Treatment-related TEAE

Group	Value	95% CI
Part A	25
Part B	22
Part C	19
Part D	18
Part E	24
Part F	6

Any grade 3 or higher TEAE

Group	Value	95% CI
Part A	17
Part B	10
Part C	18
Part D	16
Part E	18
Part F	7

Treatment-related grade 3 or higher TEAE

Group	Value	95% CI
Part A	13
Part B	9
Part C	16
Part D	12
Part E	8
Part F	4

Any treatment-emergent (TE) serious adverse event (SAE)

Group	Value	95% CI
Part A	5
Part B	4
Part C	13
Part D	4
Part E	14
Part F	4

Treatment-related TE SAE

Group	Value	95% CI
Part A	3
Part B	3
Part C	9
Part D	0
Part E	3
Part F	1

TEAE leading to treatment discontinuation

Group	Value	95% CI
Part A	11
Part B	11
Part C	12
Part D	5
Part E	9
Part F	3

Treatment-related TEAE leading to treatment discontinuation

Group	Value	95% CI
Part A	11
Part B	9
Part C	8
Part D	2
Part E	5
Part F	2

Number of Participants With Laboratory Abnormalities Secondary · Up to 30 months

Laboratory values were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.03). The CTCAE displays Grades 1 through 5, where Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe or medically significant but not immediately life-threatening, Grade 4: Life-threatening consequences, Grade 5: Death related to AE.

Hemoglobin High, Grade 1

Group	Value	95% CI
Part A	2
Part B	1
Part C	0
Part D	1
Part E	1
Part F	0

Hemoglobin High. Grade 2

Group	Value	95% CI
Part A	0
Part B	0
Part C	0
Part D	0
Part E	0
Part F	0

Hemoglobin High. Grade 3

Group	Value	95% CI
Part A	0
Part B	0
Part C	0
Part D	0
Part E	0
Part F	0

Hemoglobin High. Grade 4

Group	Value	95% CI
Part A	0
Part B	0
Part C	0
Part D	0
Part E	0
Part F	0

Hemoglobin Low, Grade 1

Group	Value	95% CI
Part A	10
Part B	6
Part C	10
Part D	9
Part E	13
Part F	4

Hemoglobin Low, Grade 2

Group	Value	95% CI
Part A	5
Part B	6
Part C	6
Part D	5
Part E	6
Part F	1

Hemoglobin Low, Grade 3

Group	Value	95% CI
Part A	1
Part B	0
Part C	1
Part D	2
Part E	0
Part F	0

Hemoglobin Low, Grade 4

Group	Value	95% CI
Part A	0
Part B	0
Part C	0
Part D	0
Part E	0
Part F	0

Complete Response Rate Secondary · Up to 81 months

Complete response rate is defined as the percentage of patients with CR

Group	Value	95% CI
Part A	70	49.8 – 86.2
Part B	64	40.7 – 82.8
Part C	75	50.9 – 91.3
Part D	67	43.0 – 85.4
Part E	30	14.7 – 49.4
Part F	43	9.9 – 81.6

Duration of Complete Response Secondary · Up to 81 months

Duration of CR per investigator was defined as the time from start of the first documentation of CR to the first documentation of tumor progression or to death due to any cause, whichever came first. For Parts E and F, the assessment was per BICR.

Group	Value	95% CI
Part A	7.4	5.1 – NA
Part B	NA	14.7 – NA
Part C	NA	2.8 – NA
Part D	NA	6.6 – NA
Part E	NA	7.4 – NA
Part F	NA	NA – NA

Duration of Objective Response Secondary · Up to 81 months

Duration of response per investigator was defined as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression (PD) based on radiographic evidence of progression or to death due to any cause, whichever came first. For Parts E and F, the assessment was per BICR.

Group	Value	95% CI
Part A	7.6	5.1 – 67.7
Part B	46.0	8.5 – NA
Part C	NA	3.6 – NA
Part D	NA	12.7 – NA
Part E	7.4	7.4 – NA
Part F	NA	11.3 – NA

Progression-free Survival Secondary · Up to 83 months

Progression-free survival (PFS) per investigator was defined as the time from start of study treatment to first documentation of tumor progression or to death due to any cause, whichever came first. For Parts E and F, the assessment was per BICR.

Group	Value	95% CI
Part A	8.6	6.3 – 40.1
Part B	47.2	10.8 – NA
Part C	32.5	4.0 – NA
Part D	NA	9.4 – NA
Part E	8.7	5.1 – NA
Part F	10.5	0.5 – NA

Disease Control Rate Secondary · Up to 81 months

Disease control rate (DCR) per investigator was defined as the percentage of subjects with CR, PR, or SD, per investigator assessment of best clinical response per Cheson 2007. For Parts E and F, the assessment was per BICR.

Group	Value	95% CI
Part A	100	87.2 – 100.0
Part B	95	77.2 – 99.9
Part C	85	62.1 – 96.8
Part D	90	69.6 – 98.8
Part E	77	57.7 – 90.1
Part F	57	18.4 – 90.1

ORR According to Lugano Criteria Per BICR (Parts E and F) Secondary · Up to 31 months

Objective response rate (ORR) per investigator was defined as the percentage of subjects with CR or PR through the end of study or prior to the start of new anti-cancer treatment (including stem cell transplant, and excluding consolidative radiotherapy) other than the study treatment.

Group	Value	95% CI
Part E	67	47.2 – 82.7
Part F	43	9.9 – 81.6

B Symptom Resolution Rate Secondary · Up to 42 weeks

B symptom resolution rate per investigator was defined as the percentage of subjects with lymphoma-related B symptoms at baseline who achieved resolution of all B symptoms at any time during the treatment period.

Group	Value	95% CI
Part A	100	47.8 – 100.0
Part B	100	54.1 – 100.0
Part C	86	42.1 – 99.6
Part D	67	22.3 – 95.7
Part E	0	NA – NA
Part F	0	NA – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: Non-serious Adverse Events, Serious Adverse Events, and All-Cause Mortality were followed for up to 122 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part A

Serious: 5/27 (19%)

Deaths: 13/27

Part B

Serious: 4/22 (18%)

Deaths: 9/22

Part C

Serious: 13/20 (65%)

Deaths: 12/20

Part D

Serious: 4/21 (19%)

Deaths: 4/21

Part E

Serious: 14/30 (47%)

Deaths: 10/30

Part F

Serious: 4/7 (57%)

Deaths: 5/7

Serious adverse events (72 terms)

Reaction	System	Part A	Part B	Part C	Part D	Part E	Part F
Nausea	Gastrointestinal disorders	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—
Acute kidney injury	Renal and urinary disorders	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—
Disseminated intravascular coagulation	Blood and lymphatic system disorders	—	—	—	—	—	—
Acute myocardial infarction	Cardiac disorders	—	—	—	—	—	—
Angina pectoris	Cardiac disorders	—	—	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—	—	—
Atrial flutter	Cardiac disorders	—	—	—	—	—	—
Cardiac failure	Cardiac disorders	—	—	—	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—	—	—	—
Tachycardia	Cardiac disorders	—	—	—	—	—	—
Inappropriate antidiuretic hormone secretion	Endocrine disorders	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—
Erosive oesophagitis	Gastrointestinal disorders	—	—	—	—	—	—
Haematochezia	Gastrointestinal disorders	—	—	—	—	—	—
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	—	—	—	—	—	—
Small intestinal obstruction	Gastrointestinal disorders	—	—	—	—	—	—
Gait disturbance	General disorders	—	—	—	—	—	—
General physical health deterioration	General disorders	—	—	—	—	—	—

Other adverse events (103 terms — click to expand)

Reaction	System	Part A	Part B	Part C	Part D	Part E	Part F
Peripheral sensory neuropathy	Nervous system disorders	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—
Chills	General disorders	—	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Infusion related reaction	Injury, poisoning and procedural complications	—	—	—	—	—	—
Weight decreased	Investigations	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—	—	—	—
Lipase increased	Investigations	—	—	—	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—
Peripheral motor neuropathy	Nervous system disorders	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Hypotension	Vascular disorders	—	—	—	—	—	—
Oral candidiasis	Infections and infestations	—	—	—	—	—	—
Amylase increased	Investigations	—	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—
Hypomagnesaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Muscular weakness	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Dry skin	Skin and subcutaneous tissue disorders	—	—	—	—	—	—

Most-reported serious reactions: Nausea, Vomiting, Febrile neutropenia, Asthenia, Pneumonia, Urinary tract infection, Acute kidney injury, Anaemia.

Data from ClinicalTrials.gov NCT01716806 adverse events section.

Sponsor's own description

This trial will study brentuximab vedotin to find out whether it is an effective treatment for Hodgkin lymphoma (HL) and peripheral T-cell lymphoma (PTCL). Participants in this study will be older or will have other conditions that make them unable to have standard chemotherapy treatment. The study will look at brentuximab vedotin alone and combined with other drugs.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Phase 2 study of frontline brentuximab vedotin monotherapy in Hodgkin lymphoma patients aged 60 years and older.
   Forero-Torres A, Holkova B, Goldschmidt J, Chen R, et al · · 2015 · cited 104× · PMID 26377597 · DOI 10.1182/blood-2015-06-644336
2. The efficacy and tolerability of adriamycin, bleomycin, vinblastine, dacarbazine and Stanford V in older Hodgkin lymphoma patients: a comprehensive analysis from the North American intergroup trial E2496.
   Evens AM, Hong F, Gordon LI, Fisher RI, et al · · 2013 · cited 103× · PMID 23356491 · DOI 10.1111/bjh.12222
3. Checkpoint blockade in Hodgkin and non-Hodgkin lymphoma.
   Merryman RW, Armand P, Wright KT, Rodig SJ. · · 2017 · cited 87× · PMID 29296917 · DOI 10.1182/bloodadvances.2017012534
4. Frontline brentuximab vedotin in combination with dacarbazine or bendamustine in patients aged ≥60 years with HL.
   Friedberg JW, Forero-Torres A, Bordoni RE, Cline VJM, et al · · 2017 · cited 69× · PMID 29038340 · DOI 10.1182/blood-2017-06-787200
5. Treatment Options for Paediatric Anaplastic Large Cell Lymphoma (ALCL): Current Standard and beyond.
   Prokoph N, Larose H, Lim MS, Burke GAA, et al · · 2018 · cited 58× · PMID 29601554 · DOI 10.3390/cancers10040099
6. Brentuximab vedotin for treatment of non-Hodgkin lymphomas: A systematic review.
   Berger GK, McBride A, Lawson S, Royball K, et al · · 2017 · cited 58× · PMID 28010897 · DOI 10.1016/j.critrevonc.2016.11.009
7. Latest advances in the management of classical Hodgkin lymphoma: the era of novel therapies.
   Mohty R, Dulery R, Bazarbachi AH, Savani M, et al · · 2021 · cited 34× · PMID 34244478 · DOI 10.1038/s41408-021-00518-z
8. Brentuximab vedotin with dacarbazine or nivolumab as frontline cHL therapy for older patients ineligible for chemotherapy.
   Friedberg JW, Bordoni R, Patel-Donnelly D, Larson T, et al · · 2024 · cited 28× · PMID 37946283 · DOI 10.1182/blood.2022019536