A Brentuximab Vedotin Trial for Patients Who Have Previously Participated in a Brentuximab Vedotin Study

• Sponsor: Seagen Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00947856
• Collaborator: Millennium Pharmaceuticals, Inc. (Industry)
• Enrollment: 110
• Locations: 17
• Arms: 2
• Duration (Months): 44
• Patients Per Site: 6.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a multicenter, open-label study to evaluate the safety and efficacy of treatment with brentuximab vedotin (SGN-35) in patients who have previously participated in an brentuximab vedotin study.

Condition or Disease	Intervention/Treatment	Phase
Disease, Hodgkin; Lymphoma, Large-Cell, Anaplastic; Lymphoma, Non-Hodgkin	Drug: brentuximab vedotin	Phase 2

Detailed Description

This is a multicenter, open-label study to evaluate single-agent brentuximab vedotin (SGN-35) treatment in patients who previously participated in a brentuximab vedotin study, including Studies SGN35-005 (NCT01100502), SGN35-007 (NCT01026233), and SGN35-008 (NCT01026415). Patients treated on this study (SGN35-006) could re-enroll on study if eligible. The study consisted of 2 arms, as follows:

• Retreatment arm: Patients with CD30-positive hematologic malignancies who experienced a complete remission (CR) or partial remission (PR) with previous brentuximab vedotin treatment on a clinical study and subsequently experienced disease progression or relapse. The purpose of this arm was to assess safety and efficacy of retreatment with brentuximab vedotin.

• Extension treatment arm: Patients with either CD30-positive hematologic or nonhematologic malignancies who completed treatment in a prior brentuximab vedotin study without unacceptable toxicity and experienced clinical benefit as assessed by the investigator. The purpose of this arm was to enable patients who participated in certain prior brentuximab vedotin trials to receive extension treatment and to assess patient safety and survival in the extension treatment setting.

Study Design

• Study Type: Interventional
• Actual Enrollment: 110 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment With SGN-35 in Patients With CD30-positive Hematologic Malignancies Who Have Previously Participated in an SGN-35 Study
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BV Retreatment Brentuximab vedotin 1.2 or 1.8 mg/kg every 3 weeks by IV infusion (retreatment after relapse)	Drug: brentuximab vedotin; Every 3 weeks by IV infusion (1.2 or 1.8 mg/kg) until disease progression, unacceptable toxicity, or study closure; Other Names: Adcetris
Experimental: BV Extension Brentuximab vedotin 1.2 or 1.8 mg/kg every 3 weeks by IV infusion (continued treatment)	Drug: brentuximab vedotin; Every 3 weeks by IV infusion (1.2 or 1.8 mg/kg) until disease progression, unacceptable toxicity, or study closure; Other Names: Adcetris

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate by Investigator [Up to approximately 38 months]

   Percentage of participants in the retreatment arm 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.

2. Adverse Events by Severity, Seriousness, and Relationship to Treatment [up to 39 months]

   Counts of participants who had adverse events or treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose on SGN35-006). 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.

3. Laboratory Abnormalities >/= Grade 3 [Up to 39 months]

   Counts of study participants with post-baseline 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.

Secondary Outcome Measures

1. Duration of Objective Response by Kaplan-Meier Analysis [Up to 38 months]

   Duration of objective response (CR + PR) on retreatment, defined as time of initial response until disease progression or death

2. Progression-free Survival by Kaplan-Meier Analysis [Up to approximately 29 months]

   Progression-free survival, defined as time from start of study treatment in the retreatment arm to disease progression per investigator or death due to any cause

3. Overall Survival [Up to approximately 41 months]

   Overall survival for both extension and retreatment arms, defined as time from start of study treatment to date of death due to any cause

4. Incidence of Antitherapeutic Antibodies [Up to 39 months]

   Counts of participants with anti-brentuximab vedotin antibodies at any time during extension treatment on Study SGN35-006 or number of retreatment experiences with anti-brentuximab vedotin antibodies at any time during retreatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participated in a previous brentuximab vedotin study.

• CD30-positive hematologic malignancy.

• At a minimum, experienced clinical benefit in the prior brentuximab vedotin study. For retreatment, patients must have previously achieved either complete or partial remission with brentuximab vedotin and experienced disease progression after discontinuing the prior brentuximab vedotin study.

Exclusion Criteria:

Withdrew consent to participate in any prior brentuximab vedotin study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294-3300
2	City of Hope National Medical Center	Duarte	California	United States	91010
3	Stanford Cancer Center	Stanford	California	United States	94305
4	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
5	University of Miami Miller School of Medicine / Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
6	Loyola University Medical Center - Cardinal Bernadin Cancer Center	Maywood	Illinois	United States	60153
7	St. Francis Medical Group Oncology & Hematology Specialists	Indianapolis	Indiana	United States	46237
8	Karmanos Cancer Institute / Wayne State University	Detroit	Michigan	United States	48201
9	Washington University School of Medicine	St. Louis	Missouri	United States	63110
10	The John Theurer Cancer Center, Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
11	NYU Clinical Cancer Center	New York	New York	United States	10016
12	Columbia University Medical Center	New York	New York	United States	10019
13	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
14	Charles A. Sammons Cancer Center	Dallas	Texas	United States	75246
15	MD Anderson Cancer Center /The University of Texas	Houston	Texas	United States	77030
16	Seattle Cancer Care Alliance / University of Washington Medical Center	Seattle	Washington	United States	98109-1023
17	Hopital Saint-Louis/Service d'Hematologie	Paris	Cedex 10	France	75475

Sponsors and Collaborators

• Seagen Inc.
• Millennium Pharmaceuticals, Inc.

Investigators

• Study Director: Laurie Grove, PA-C, Seagen Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Seagen Inc.
• ClinicalTrials.gov Identifier: NCT00947856
• Other Study ID Numbers: SGN35-006; 2010-019932-11
• First Posted: Jul 28, 2009
• Last Update Posted: Feb 2, 2017
• Last Verified: Dec 1, 2016

• Keywords provided by Seagen Inc.: Antibodies, Monoclonal; Antibody-Drug Conjugate; Antigens, CD30; Drug Therapy; Hematologic Diseases; Immunotherapy; Monomethylauristatin E
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Large-Cell, Anaplastic; Hodgkin Disease; Brentuximab Vedotin

Study Results

Participant Flow

Recruitment Details	Jul 2009 - Mar 2013

Arm/Group Title	BV Extension	BV Retreatment
Arm/Group Description	Brentuximab vedotin 1.2 or 1.8 mg/kg every 3 weeks by IV infusion (continued treatment)	Brentuximab vedotin 1.2 or 1.8 mg/kg every 3 weeks by IV infusion (retreatment after relapse)
Period Title: Treatment Period
STARTED	78	32
COMPLETED	0	0
NOT COMPLETED	78	32
Period Title: Treatment Period
STARTED	78	32
COMPLETED	27	9
NOT COMPLETED	51	23

Baseline Characteristics

Arm/Group Title	BV Extension	BV Retreatment	Total
Arm/Group Description	Brentuximab vedotin 1.2 or 1.8 mg/kg every 3 weeks by IV infusion (continued treatment)	Brentuximab vedotin 1.2 or 1.8 mg/kg every 3 weeks by IV infusion (retreatment after relapse)	Total of all reporting groups
Overall Participants	78	32	110
Age, Customized (years) [Median (Full Range) ]
Median (Full Range) [years]	32	37	33.5
Gender (Count of Participants)
Female	35 44.9%	17 53.1%	52 47.3%
Male	43 55.1%	15 46.9%	58 52.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 3.8%	0 0%	3 2.7%
Native Hawaiian or Other Pacific Islander	1 1.3%	0 0%	1 0.9%
Black or African American	7 9%	4 12.5%	11 10%
White	66 84.6%	27 84.4%	93 84.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 1.3%	1 3.1%	2 1.8%
Region of Enrollment (participants) [Number]
France	0 0%	3 9.4%	3 2.7%
United States	78 100%	29 90.6%	107 97.3%
Eastern Cooperative Oncology Group Performance Status (participants) [Number]
0	47 60.3%	12 37.5%	59 53.6%
1	30 38.5%	18 56.3%	48 43.6%
2	0 0%	2 6.3%	2 1.8%
3-5	0 0%	0 0%	0 0%
Missing	1 1.3%	0 0%	1 0.9%
Disease diagnosis (participants) [Number]
Hodgkin lymphoma (HL)	68 87.2%	21 65.6%	89 80.9%
Systemic anaplastic large cell lymphoma (ALCL)	8 10.3%	8 25%	16 14.5%
Other	2 2.6%	3 9.4%	5 4.5%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate by Investigator
Description	Percentage of participants in the retreatment arm 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.
Time Frame	Up to approximately 38 months

Outcome Measure Data

Analysis Population Description

Any patient who received retreatment and had postbaseline response results; 1 HL patient did not have postbaseline response results and 3 ALCL patients were retreated more than once.

Arm/Group Title	BV Retreatment - HL	BV Retreatment - ALCL	BV Retreatment - Other	BV Retreatment Total
Arm/Group Description	Patients with Hodgkin lymphoma (HL) enrolled and treated on the retreatment arm	Patients with anaplastic large cell lymphoma (ALCL) enrolled and treated on the retreatment arm	Patients with other disease diagnoses enrolled and treated on the retreatment arm	All patients enrolled and treated on the retreatment arm, including 3 patients retreated more than once
Measure Participants	21	8	3	32
Measure Retreatment Experiences	20	11	3	34
Number (95% Confidence Interval) [percentage of retreatment experiences]	60	91	33	68

2. Primary Outcome

Title	Adverse Events by Severity, Seriousness, and Relationship to Treatment
Description	Counts of participants who had adverse events or treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose on SGN35-006). 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.
Time Frame	up to 39 months

Outcome Measure Data

Analysis Population Description

All participants who received treatment

Arm/Group Title	BV Extension	BV Retreatment
Arm/Group Description	Brentuximab vedotin 1.2 or 1.8 mg/kg every 3 weeks by IV infusion (continued treatment)	Brentuximab vedotin 1.2 or 1.8 mg/kg every 3 weeks by IV infusion (retreatment after relapse)
Measure Participants	78	32
Any TEAE	75 96.2%	31 96.9%
TEAE related to study drug	65 83.3%	27 84.4%
TEAE with severity grade >/=3	37 47.4%	16 50%
Discontinued treatment due to adverse event	13 16.7%	9 28.1%
Serious adverse event	16 20.5%	9 28.1%
Serious adverse event related to study drug	10 12.8%	4 12.5%

3. Primary Outcome

Title	Laboratory Abnormalities >/= Grade 3
Description	Counts of study participants with post-baseline 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.
Time Frame	Up to 39 months

Outcome Measure Data

Analysis Population Description

All participants who received treatment

Arm/Group Title	BV Extension	BV Retreatment
Arm/Group Description	Brentuximab vedotin 1.2 or 1.8 mg/kg every 3 weeks by IV infusion (continued treatment)	Brentuximab vedotin 1.2 or 1.8 mg/kg every 3 weeks by IV infusion (retreatment after relapse)
Measure Participants	78	32
Any >/= Grade 3 laboratory abnormality	29 37.2%	12 37.5%
Lymphocytes (low)	16 20.5%	8 25%
Leukocytes (low)	3 3.8%	3 9.4%
Neutrophils (low)	7 9%	3 9.4%
Phosphate (low)	7 9%	3 9.4%
Platelets (low)	4 5.1%	3 9.4%
Aspartate aminotransferase (high)	1 1.3%	2 6.3%
Glucose (high)	3 3.8%	2 6.3%
Alanine aminotransferase (high)	1 1.3%	1 3.1%
Bilirubin (high)	0 0%	1 3.1%
Calcium (low)	0 0%	1 3.1%
Hemoglobin (low)	1 1.3%	1 3.1%
Potassium (low)	0 0%	1 3.1%
Sodium (low)	2 2.6%	0 0%

4. Secondary Outcome

Title	Duration of Objective Response by Kaplan-Meier Analysis
Description	Duration of objective response (CR + PR) on retreatment, defined as time of initial response until disease progression or death
Time Frame	Up to 38 months

Outcome Measure Data

Analysis Population Description

Participants with objective response among those who received retreatment

Arm/Group Title	BV Retreatment - HL	BV Retreatment - ALCL	BV Retreatment - Other	BV Retreatment Total
Arm/Group Description	Patients with Hodgkin lymphoma (HL) enrolled and treated on the retreatment arm	Patients with anaplastic large cell lymphoma (ALCL) enrolled and treated on the retreatment arm	Patients with other disease diagnoses enrolled and treated on the retreatment arm	All patients enrolled and treated on the retreatment arm, including 3 patients retreated more than once
Measure Participants	21	8	3	32
Measure Retreatment Experiences	12	10	1	23
Median (95% Confidence Interval) [months]	9.2	8.8	NA	9.2

5. Secondary Outcome

Title	Progression-free Survival by Kaplan-Meier Analysis
Description	Progression-free survival, defined as time from start of study treatment in the retreatment arm to disease progression per investigator or death due to any cause
Time Frame	Up to approximately 29 months

Outcome Measure Data

Analysis Population Description

Any patient who received retreatment and had postbaseline response results; 1 HL patient did not have postbaseline response results and 3 ALCL patients were retreated more than once.

Arm/Group Title	BV Retreatment - HL	BV Retreatment - ALCL	BV Retreatment - Other	BV Retreatment Total
Arm/Group Description	Patients with Hodgkin lymphoma (HL) enrolled and treated on the retreatment arm	Patients with anaplastic large cell lymphoma (ALCL) enrolled and treated on the retreatment arm	Patients with other disease diagnoses enrolled and treated on the retreatment arm	All patients enrolled and treated on the retreatment arm, including 3 patients retreated more than once
Measure Participants	21	8	3	32
Measure Retreatment Experiences	20	11	3	34
Median (95% Confidence Interval) [months]	9.9	12.9	4.4	9.9

6. Secondary Outcome

Title	Overall Survival
Description	Overall survival for both extension and retreatment arms, defined as time from start of study treatment to date of death due to any cause
Time Frame	Up to approximately 41 months

Outcome Measure Data

Analysis Population Description

Patients who received treatment on the extension arm, and patients who received retreatment and had postbaseline response results; 1 HL patient on the retreatment arm did not have postbaseline response results and 3 ALCL patients on the retreatment arm were retreated more than once.

Arm/Group Title	BV Extension Total	BV Retreatment - HL	BV Retreatment - ALCL	BV Retreatment - Other	BV Retreatment Total
Arm/Group Description	All patients enrolled and treated on the extension arm	Patients with Hodgkin lymphoma (HL) enrolled and treated on the retreatment arm	Patients with anaplastic large cell lymphoma (ALCL) enrolled and treated on the retreatment arm	Patients with other disease diagnoses enrolled and treated on the retreatment arm	All patients enrolled and treated on the retreatment arm, including 3 patients retreated more than once
Measure Participants	78	21	8	3	32
Measure Retreatment or Extension Trt Experiences	78	20	11	3	34
Median (95% Confidence Interval) [months]	NA	NA	NA	NA	NA

7. Secondary Outcome

Title	Incidence of Antitherapeutic Antibodies
Description	Counts of participants with anti-brentuximab vedotin antibodies at any time during extension treatment on Study SGN35-006 or number of retreatment experiences with anti-brentuximab vedotin antibodies at any time during retreatment
Time Frame	Up to 39 months

Outcome Measure Data

Analysis Population Description

Any patient who received extension treatment or retreatment and had baseline and postbaseline sample results; 1 HL patient on the retreatment arm did not have postbaseline sample results and 3 ALCL patients on the retreatment arm were retreated more than once and had samples.

Arm/Group Title	BV Extension	BV Retreatment
Arm/Group Description	Brentuximab vedotin 1.2 or 1.8 mg/kg every 3 weeks by IV infusion (continued treatment)	Brentuximab vedotin 1.2 or 1.8 mg/kg every 3 weeks by IV infusion (retreatment after relapse)
Measure Participants	78	31
Measure Retreatment or Extension Txt Experiences	78	34
Number [participants or experiences]	15 19.2%	12 37.5%

Adverse Events

Adverse Event Reporting Description	Treatment-emergent adverse events (TEAEs) defined as newly occurring (not present at baseline) or worsening after first dose of investigational product on Study SGN35-006
Arm/Group Title	BV Extension		BV Retreatment
Arm/Group Description	Brentuximab vedotin 1.2 or 1.8 mg/kg every 3 weeks by IV infusion		Brentuximab vedotin 1.2 or 1.8 mg/kg every 3 weeks by IV infusion
All Cause Mortality
	BV Extension		BV Retreatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	BV Extension		BV Retreatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/78 (20.5%)		9/32 (28.1%)
Blood and lymphatic system disorders
Febrile neutropenia	0/78 (0%)		1/32 (3.1%)
Leukocytosis	0/78 (0%)		1/32 (3.1%)
Methaemoglobinaemia	0/78 (0%)		1/32 (3.1%)
Thrombotic thrombocytopenic purpura	0/78 (0%)		1/32 (3.1%)
Neutropenia	1/78 (1.3%)		0/32 (0%)
Thrombocytopenia	1/78 (1.3%)		0/32 (0%)
Eye disorders
Glaucoma	0/78 (0%)		1/32 (3.1%)
Necrotising retinitis	0/78 (0%)		1/32 (3.1%)
Gastrointestinal disorders
Gastrointestinal obstruction	0/78 (0%)		1/32 (3.1%)
Nausea	1/78 (1.3%)		1/32 (3.1%)
Pancreatitis	0/78 (0%)		1/32 (3.1%)
Peptic ulcer	0/78 (0%)		1/32 (3.1%)
Vomiting	1/78 (1.3%)		1/32 (3.1%)
Small intestine obstruction	1/78 (1.3%)		0/32 (0%)
General disorders
Fatigue	1/78 (1.3%)		1/32 (3.1%)
Mucosal inflammation	1/78 (1.3%)		0/32 (0%)
Immune system disorders
Graft versus host disease	0/78 (0%)		1/32 (3.1%)
Anaphylactic reaction	1/78 (1.3%)		0/32 (0%)
Infections and infestations
Bacteraemia	0/78 (0%)		1/32 (3.1%)
Bronchitis viral	0/78 (0%)		1/32 (3.1%)
Bronchopulmonary aspergillosis	0/78 (0%)		1/32 (3.1%)
Herpes zoster disseminated	0/78 (0%)		1/32 (3.1%)
Pneumonia	3/78 (3.8%)		2/32 (6.3%)
Atypical pneumonia	1/78 (1.3%)		0/32 (0%)
Gangrene	1/78 (1.3%)		0/32 (0%)
Gastrointestinal candidiasis	1/78 (1.3%)		0/32 (0%)
Influenza	1/78 (1.3%)		0/32 (0%)
Pneumocystis jiroveci pneumonia	1/78 (1.3%)		0/32 (0%)
Pneumonia influenzal	1/78 (1.3%)		0/32 (0%)
Pneumonia pseudomonas aeruginosa	1/78 (1.3%)		0/32 (0%)
Pseudomonal sepsis	1/78 (1.3%)		0/32 (0%)
Respiratory syncytial virus bronchiolitis	1/78 (1.3%)		0/32 (0%)
Injury, poisoning and procedural complications
Hip fracture	1/78 (1.3%)		0/32 (0%)
Metabolism and nutrition disorders
Dehydration	0/78 (0%)		2/32 (6.3%)
Failure to thrive	0/78 (0%)		1/32 (3.1%)
Hypercalcaemia	0/78 (0%)		1/32 (3.1%)
Hyperglycaemia	0/78 (0%)		2/32 (6.3%)
Hyponatraemia	1/78 (1.3%)		0/32 (0%)
Metabolic acidosis	1/78 (1.3%)		0/32 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/78 (0%)		1/32 (3.1%)
Back pain	0/78 (0%)		1/32 (3.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukemia	1/78 (1.3%)		0/32 (0%)
Hodgkin's disease	1/78 (1.3%)		0/32 (0%)
Oesophageal carcinoma	1/78 (1.3%)		0/32 (0%)
Nervous system disorders
Peripheral motor neuropathy	2/78 (2.6%)		1/32 (3.1%)
Peripheral sensory neuropathy	0/78 (0%)		2/32 (6.3%)
Extrapyramidal disorder	1/78 (1.3%)		0/32 (0%)
Psychiatric disorders
Mental status changes	1/78 (1.3%)		2/32 (6.3%)
Renal and urinary disorders
Renal failure acute	1/78 (1.3%)		0/32 (0%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	0/78 (0%)		1/32 (3.1%)
Respiratory failure	0/78 (0%)		1/32 (3.1%)
Dyspnoea	1/78 (1.3%)		0/32 (0%)
Pneumonitis	2/78 (2.6%)		0/32 (0%)
Pulmonary haemorrhage	1/78 (1.3%)		0/32 (0%)
Respiratory acidosis	1/78 (1.3%)		0/32 (0%)
Skin and subcutaneous tissue disorders
Rash erythematous	1/78 (1.3%)		0/32 (0%)
Vascular disorders
Hypotension	1/78 (1.3%)		0/32 (0%)
Other (Not Including Serious) Adverse Events
	BV Extension		BV Retreatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	75/78 (96.2%)		31/32 (96.9%)
Blood and lymphatic system disorders
Anaemia	7/78 (9%)		7/32 (21.9%)
Neutropenia	10/78 (12.8%)		3/32 (9.4%)
Thrombocytopenia	4/78 (5.1%)		4/32 (12.5%)
Cardiac disorders
Tachycardia	4/78 (5.1%)		2/32 (6.3%)
Endocrine disorders
Adrenal insufficiency	0/78 (0%)		2/32 (6.3%)
Eye disorders
Vision blurred	0/78 (0%)		2/32 (6.3%)
Gastrointestinal disorders
Abdominal pain	8/78 (10.3%)		3/32 (9.4%)
Abdominal pain upper	0/78 (0%)		2/32 (6.3%)
Constipation	10/78 (12.8%)		5/32 (15.6%)
Diarrhoea	15/78 (19.2%)		12/32 (37.5%)
Dyspepsia	3/78 (3.8%)		3/32 (9.4%)
Gastrooesophageal reflux disease	1/78 (1.3%)		3/32 (9.4%)
Nausea	19/78 (24.4%)		12/32 (37.5%)
Vomiting	12/78 (15.4%)		0/32 (0%)
General disorders
Chills	5/78 (6.4%)		2/32 (6.3%)
Fatigue	23/78 (29.5%)		11/32 (34.4%)
Infusion site extravasation	0/78 (0%)		2/32 (6.3%)
Non-cardiac chest pain	6/78 (7.7%)		4/32 (12.5%)
Oedema peripheral	7/78 (9%)		5/32 (15.6%)
Pyrexia	20/78 (25.6%)		8/32 (25%)
Chest discomfort	4/78 (5.1%)		0/32 (0%)
Pain	6/78 (7.7%)		0/32 (0%)
Immune system disorders
Hypogammaglobulinaemia	0/78 (0%)		2/32 (6.3%)
Infections and infestations
Oral candidiasis	0/78 (0%)		3/32 (9.4%)
Sinusitis	5/78 (6.4%)		4/32 (12.5%)
Upper respiratory tract infection	25/78 (32.1%)		6/32 (18.8%)
Urinary tract infection	0/78 (0%)		3/32 (9.4%)
Herpes zoster	7/78 (9%)		0/32 (0%)
Pneumonia	5/78 (6.4%)		0/32 (0%)
Injury, poisoning and procedural complications
Skin injury	0/78 (0%)		3/32 (9.4%)
Investigations
Weight decreased	5/78 (6.4%)		3/32 (9.4%)
Metabolism and nutrition disorders
Decreased appetite	11/78 (14.1%)		3/32 (9.4%)
Dehydration	0/78 (0%)		2/32 (6.3%)
Hyperglycaemia	0/78 (0%)		2/32 (6.3%)
Hypocalcaemia	0/78 (0%)		2/32 (6.3%)
Hypokalaemia	6/78 (7.7%)		5/32 (15.6%)
Hypophosphataemia	5/78 (6.4%)		4/32 (12.5%)
Hypomagnesaemia	4/78 (5.1%)		0/32 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	12/78 (15.4%)		7/32 (21.9%)
Back pain	8/78 (10.3%)		5/32 (15.6%)
Muscle spasms	12/78 (15.4%)		4/32 (12.5%)
Myalgia	11/78 (14.1%)		3/32 (9.4%)
Muscular weakness	5/78 (6.4%)		0/32 (0%)
Pain in extremity	4/78 (5.1%)		0/32 (0%)
Nervous system disorders
Dizziness	6/78 (7.7%)		5/32 (15.6%)
Headache	10/78 (12.8%)		9/32 (28.1%)
Paraesthesia	4/78 (5.1%)		2/32 (6.3%)
Peripheral motor neuropathy	4/78 (5.1%)		8/32 (25%)
Peripheral sensory neuropathy	36/78 (46.2%)		17/32 (53.1%)
Syncope	0/78 (0%)		2/32 (6.3%)
Psychiatric disorders
Anxiety	4/78 (5.1%)		3/32 (9.4%)
Confusional state	0/78 (0%)		2/32 (6.3%)
Depression	1/78 (1.3%)		2/32 (6.3%)
Insomnia	6/78 (7.7%)		4/32 (12.5%)
Respiratory, thoracic and mediastinal disorders
Cough	16/78 (20.5%)		6/32 (18.8%)
Dyspnoea	7/78 (9%)		8/32 (25%)
Nasal congestion	4/78 (5.1%)		2/32 (6.3%)
Wheezing	3/78 (3.8%)		3/32 (9.4%)
Skin and subcutaneous tissue disorders
Alopecia	12/78 (15.4%)		4/32 (12.5%)
Erythema	0/78 (0%)		2/32 (6.3%)
Night sweats	6/78 (7.7%)		3/32 (9.4%)
Pruritus	10/78 (12.8%)		4/32 (12.5%)
Rash erythematous	0/78 (0%)		2/32 (6.3%)
Rash generalised	0/78 (0%)		2/32 (6.3%)
Skin lesion	0/78 (0%)		2/32 (6.3%)
Vascular disorders
Flushing	0/78 (0%)		3/32 (9.4%)
Hypertension	3/78 (3.8%)		2/32 (6.3%)
Hypotension	4/78 (5.1%)		2/32 (6.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.