Trial Outcomes & Findings for A Pivotal Open-Label Trial of Brentuximab Vedotin for Hodgkin Lymphoma (NCT NCT00848926)

NCT ID: NCT00848926

Last Updated: 2017-03-13

Results Overview

Percentage of participants who achieved a best response of complete remission (CR, disappearance of all evidence of disease) or partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 102 participants
• Primary outcome timeframe: up to 12 months
• Results posted on: 2017-03-13

Participant Flow

Enrollment period: Feb 2009 - Aug 2009

Participant milestones

Measure	Brentuximab Vedotin Brentuximab vedotin 1.8 mg/kg every 3 weeks by intravenous (IV) infusion
Treatment Period STARTED	102
Treatment Period COMPLETED	18
Treatment Period NOT COMPLETED	84
Follow-up Period STARTED	102
Follow-up Period COMPLETED	90
Follow-up Period NOT COMPLETED	12

Reasons for withdrawal

Measure	Brentuximab Vedotin Brentuximab vedotin 1.8 mg/kg every 3 weeks by intravenous (IV) infusion
Treatment Period Progressive disease	45
Treatment Period Adverse Event	20
Treatment Period Physician Decision	12
Treatment Period Withdrawal by Subject	7
Follow-up Period Lost to Follow-up	7
Follow-up Period Withdrawal by Subject	3
Follow-up Period Other	2

Baseline Characteristics

A Pivotal Open-Label Trial of Brentuximab Vedotin for Hodgkin Lymphoma

Baseline characteristics by cohort

Measure	Brentuximab Vedotin n=102 Participants Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Age, Customized	31.0 years n=93 Participants
Sex: Female, Male Female	54 Participants n=93 Participants
Sex: Female, Male Male	48 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	7 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	5 Participants n=93 Participants
Race (NIH/OMB) White	89 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants
Eastern Cooperative Oncology Group Performance Status 0	42 participants n=93 Participants
Eastern Cooperative Oncology Group Performance Status 1	60 participants n=93 Participants
Eastern Cooperative Oncology Group Performance Status 2-5	0 participants n=93 Participants

PRIMARY outcome

Timeframe: up to 12 months

Population: Intention to treat

Percentage of participants who achieved a best response of complete remission (CR, disappearance of all evidence of disease) or partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.

Outcome measures

Measure	Brentuximab Vedotin n=102 Participants Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Objective Response Rate by Independent Review Group	75 percent of participants Interval 64.9 to 82.6

SECONDARY outcome

Timeframe: up to 12 months

Population: Intention to treat

Percentage of participants who achieved a best response of CR (disappearance of all evidence of disease) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.

Outcome measures

Measure	Brentuximab Vedotin n=102 Participants Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Complete Remission Rate by Independent Review Group	33 percent of participants Interval 24.3 to 43.4

SECONDARY outcome

Timeframe: up to approximately 4 years

Population: Participants with objective response among the intention to treat population

Duration of objective response (CR + PR) by independent review group, defined as time of initial response until disease progression or death.

Outcome measures

Measure	Brentuximab Vedotin n=76 Participants Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Duration of Objective Response by Kaplan-Meier Analysis	6.7 months Interval 3.6 to 14.8

SECONDARY outcome

Timeframe: up to approximately 4 years

Population: Participants with complete remission among the intention to treat population

Duration of response from start of first objective tumor response (CR or PR) by independent review group to disease progression or death due to any cause in participants with CR.

Outcome measures

Measure	Brentuximab Vedotin n=34 Participants Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Duration of Objective Response in Participants With Complete Remission by Kaplan-Meier Analysis	27.9 months Interval 10.8 to Insufficient number of events to estimate upper bound

SECONDARY outcome

Timeframe: up to approximately 4 years

Population: Intention to treat

Time from start of study treatment to disease progression per independent review group or death due to any cause.

Outcome measures

Measure	Brentuximab Vedotin n=102 Participants Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Progression-free Survival by Kaplan-Meier Analysis	5.6 months Interval 5.0 to 9.0

SECONDARY outcome

Timeframe: up to approximately 6 years

Population: Intention to treat

Time from start of study treatment to date of death due to any cause.

Outcome measures

Measure	Brentuximab Vedotin n=102 Participants Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Overall Survival	40.5 months Interval 28.7 to 61.9

SECONDARY outcome

Timeframe: up to 12 months

Population: All participants who received treatment

Counts of participants who had adverse events or treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 3.0) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death). Relatedness to study drug was assessed by the investigator (Yes/No). Participants with multiple occurrences of an adverse event within a category are counted once within the category.

Outcome measures

Measure	Brentuximab Vedotin n=102 Participants Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Adverse Events by Severity, Seriousness, and Relationship to Treatment TEAE related to study drug	94 participants
Adverse Events by Severity, Seriousness, and Relationship to Treatment TEAE with severity grade >/=3	56 participants
Adverse Events by Severity, Seriousness, and Relationship to Treatment Any TEAE	100 participants
Adverse Events by Severity, Seriousness, and Relationship to Treatment Serious adverse event	25 participants
Adverse Events by Severity, Seriousness, and Relationship to Treatment Serious adverse event related to study drug	14 participants
Adverse Events by Severity, Seriousness, and Relationship to Treatment Discontinued treatment due to adverse event	20 participants

SECONDARY outcome

Timeframe: up to 12 months

Population: All participants who received treatment

Counts of study participants with post-baseline hematology laboratory abnormalities of Grade 3 or greater per NCI CTCAE version 3.0. Participants with multiple occurrences of a laboratory abnormality within a category are counted once in that category.

Outcome measures

Measure	Brentuximab Vedotin n=102 Participants Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Hematology Laboratory Abnormalities >/= Grade 3 Any >/= Grade 3 hematology laboratory abnormality	35 participants
Hematology Laboratory Abnormalities >/= Grade 3 Hemoglobin (low)	7 participants
Hematology Laboratory Abnormalities >/= Grade 3 Leukocytes (low)	6 participants
Hematology Laboratory Abnormalities >/= Grade 3 Lymphocytes (low)	20 participants
Hematology Laboratory Abnormalities >/= Grade 3 Neutrophils (low)	12 participants
Hematology Laboratory Abnormalities >/= Grade 3 Platelets (low)	7 participants

SECONDARY outcome

Timeframe: up to 12 months

Population: All participants who received treatment

Counts of study participants with post-baseline chemistry laboratory abnormalities of Grade 3 or greater per NCI CTCAE version 3.0. Participants with multiple occurrences of a laboratory abnormality within a category are counted once in that category.

Outcome measures

Measure	Brentuximab Vedotin n=102 Participants Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Chemistry Laboratory Abnormalities >/= Grade 3 Glucose (high)	7 participants
Chemistry Laboratory Abnormalities >/= Grade 3 Potassium (low)	2 participants
Chemistry Laboratory Abnormalities >/= Grade 3 Sodium (high)	1 participants
Chemistry Laboratory Abnormalities >/= Grade 3 Any >/= Grade 3 chemistry laboratory abnormality	14 participants
Chemistry Laboratory Abnormalities >/= Grade 3 Alanine aminotransferase (high)	1 participants
Chemistry Laboratory Abnormalities >/= Grade 3 Albumin (low)	1 participants
Chemistry Laboratory Abnormalities >/= Grade 3 Calcium (low)	1 participants
Chemistry Laboratory Abnormalities >/= Grade 3 Urate (high)	1 participants

SECONDARY outcome

Timeframe: 3 weeks

Population: All participants who received treatment

Area under the serum concentration-time curve from time 0 to 21 days following the first dose of brentuximab vedotin

Outcome measures

Measure	Brentuximab Vedotin n=102 Participants Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Area Under the Curve	88 day * microgram/mL Geometric Coefficient of Variation 46

SECONDARY outcome

Timeframe: 3 weeks

Population: All participants who received treatment

Maximum serum concentration from 0 to 21 days following the first dose of brentuximab vedotin

Outcome measures

Measure	Brentuximab Vedotin n=102 Participants Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Maximum Serum Concentration	35 microgram/mL Geometric Coefficient of Variation 17

SECONDARY outcome

Timeframe: 3 weeks

Population: All participants who received treatment

Time of maximum serum concentration from 0 to 21 days following the first dose of brentuximab vedotin

Outcome measures

Measure	Brentuximab Vedotin n=102 Participants Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Time of Maximum Serum Concentration	0.02 days Interval 0.02 to 0.02

OTHER_PRE_SPECIFIED outcome

Timeframe: up to 12 months

Population: Participants with B symptoms at baseline

Percentage of participants with lymphoma-related symptoms (B symptoms: fever, night sweats, or weight loss >10%) at baseline who achieved resolution of all B symptoms at any time during the treatment period.

Outcome measures

Measure	Brentuximab Vedotin n=35 Participants Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
B Symptom Resolution	77 percent of participants Interval 59.9 to 89.6

Adverse Events

Brentuximab Vedotin

Serious events: 25 serious events

Other events: 97 other events

Deaths: 0 deaths

Serious adverse events

Measure	Brentuximab Vedotin n=102 participants at risk Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Blood and lymphatic system disorders Thrombocytopenia	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Gastrointestinal disorders Abdominal pain	2.0% 2/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Gastrointestinal disorders Abdominal pain upper	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Gastrointestinal disorders Diarrhoea	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Gastrointestinal disorders Gastrointestinal haemorrhage	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Gastrointestinal disorders Haematemesis	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Gastrointestinal disorders Intestinal perforation	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Gastrointestinal disorders Nausea	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
General disorders Pyrexia	2.0% 2/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Infections and infestations Bronchitis	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Infections and infestations Candidiasis	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Infections and infestations Cellulitis	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Infections and infestations H1N1 influenza	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Infections and infestations Lung infection	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Infections and infestations Pneumocystis jiroveci pneumonia	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Infections and infestations Pneumonia	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Infections and infestations Pyelonephritis	2.0% 2/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Infections and infestations Septic shock	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Infections and infestations Soft tissue infection	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Infections and infestations Staphylococcal bacteraemia	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Infections and infestations Urinary tract infection staphylococcal	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Injury, poisoning and procedural complications Wrist fracture	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Metabolism and nutrition disorders Hyperglycaemia	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Musculoskeletal and connective tissue disorders Flank pain	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Musculoskeletal and connective tissue disorders Muscular weakness	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large B-cell lymphoma	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hodgkin's disease recurrent	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Nervous system disorders Demyelinating polyneuropathy	2.0% 2/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Nervous system disorders Diabetic coma	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Nervous system disorders Peripheral motor neuropathy	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Psychiatric disorders Mental status changes	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.0% 2/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Respiratory, thoracic and mediastinal disorders Pneumothorax	2.0% 2/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.0% 2/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Skin and subcutaneous tissue disorders Stevens-Johnson syndrome	0.98% 1/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)

Other adverse events

Measure	Brentuximab Vedotin n=102 participants at risk Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Blood and lymphatic system disorders Anaemia	8.8% 9/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Blood and lymphatic system disorders Lymphadenopathy	10.8% 11/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Blood and lymphatic system disorders Neutropenia	21.6% 22/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Blood and lymphatic system disorders Thrombocytopenia	6.9% 7/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Gastrointestinal disorders Abdominal pain	14.7% 15/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Gastrointestinal disorders Constipation	15.7% 16/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Gastrointestinal disorders Diarrhoea	36.3% 37/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Gastrointestinal disorders Nausea	42.2% 43/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Gastrointestinal disorders Vomiting	21.6% 22/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
General disorders Chills	12.7% 13/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
General disorders Fatigue	46.1% 47/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
General disorders Pain	6.9% 7/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
General disorders Pyrexia	29.4% 30/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Infections and infestations Bronchitis	7.8% 8/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Infections and infestations Herpes zoster	6.9% 7/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Infections and infestations Sinusitis	8.8% 9/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Infections and infestations Upper respiratory tract infection	37.3% 38/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Infections and infestations Urinary tract infection	5.9% 6/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Investigations Weight decrease	5.9% 6/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Metabolism and nutrition disorders Decreased appetite	10.8% 11/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Musculoskeletal and connective tissue disorders Arthralgia	18.6% 19/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Musculoskeletal and connective tissue disorders Back pain	13.7% 14/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Musculoskeletal and connective tissue disorders Bone pain	7.8% 8/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Musculoskeletal and connective tissue disorders Muscle spasms	8.8% 9/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Musculoskeletal and connective tissue disorders Myalgia	16.7% 17/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Musculoskeletal and connective tissue disorders Neck pain	5.9% 6/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Musculoskeletal and connective tissue disorders Pain in extremity	9.8% 10/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hodgkin's disease recurrent	5.9% 6/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Nervous system disorders Dizziness	10.8% 11/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Nervous system disorders Headache	18.6% 19/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Nervous system disorders Peripheral motor neuropathy	10.8% 11/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Nervous system disorders Peripheral sensory neuropathy	47.1% 48/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Psychiatric disorders Anxiety	10.8% 11/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Psychiatric disorders Depression	7.8% 8/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Psychiatric disorders Insomnia	13.7% 14/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Respiratory, thoracic and mediastinal disorders Cough	20.6% 21/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.7% 13/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.9% 6/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	10.8% 11/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Respiratory, thoracic and mediastinal disorders Productive cough	5.9% 6/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Skin and subcutaneous tissue disorders Alopecia	12.7% 13/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Skin and subcutaneous tissue disorders Hyperhidrosis	5.9% 6/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Skin and subcutaneous tissue disorders Night sweats	11.8% 12/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Skin and subcutaneous tissue disorders Pruritus	15.7% 16/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Skin and subcutaneous tissue disorders Rash	13.7% 14/102 • Treatment-emergent adverse events through 30 days after last dose (up to 12 months)

Additional Information

Chief Medical Officer

Seattle Genetics, Inc.

Phone: 855-473-2436

Email: medinfo@seagen.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60