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

• Sponsor: Seagen Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00848926
• Collaborator: Millennium Pharmaceuticals, Inc. (Industry)
• Enrollment: 102
• Locations: 27
• Arm: 1
• Duration (Months): 74.9
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a single-arm, open-label, multicenter, pivotal clinical trial to evaluate the efficacy and safety of brentuximab vedotin (SGN-35) as a single agent in patients with relapsed or refractory Hodgkin lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Disease, Hodgkin	Drug: brentuximab vedotin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 102 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pivotal Study of SGN-35 in Treatment of Patients With Relapsed or Refractory Hodgkin Lymphoma (HL)
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Aug 1, 2010
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Brentuximab vedotin	Drug: brentuximab vedotin; 1.8 mg/kg every 3 weeks by intravenous infusion; Other Names: SGN-35 ADCETRIS

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate by Independent Review Group [up to 12 months]

   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.

Secondary Outcome Measures

1. Complete Remission Rate by Independent Review Group [up to 12 months]

   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.

2. Duration of Objective Response by Kaplan-Meier Analysis [up to approximately 4 years]

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

3. Duration of Objective Response in Participants With Complete Remission by Kaplan-Meier Analysis [up to approximately 4 years]

   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.

4. Progression-free Survival by Kaplan-Meier Analysis [up to approximately 4 years]

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

5. Overall Survival [up to approximately 6 years]

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

6. Adverse Events by Severity, Seriousness, and Relationship to Treatment [up to 12 months]

   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.

7. Hematology Laboratory Abnormalities >/= Grade 3 [up to 12 months]

   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.

8. Chemistry Laboratory Abnormalities >/= Grade 3 [up to 12 months]

   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.

9. Area Under the Curve [3 weeks]

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

10. Maximum Serum Concentration [3 weeks]

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

11. Time of Maximum Serum Concentration [3 weeks]

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

Other Outcome Measures

1. B Symptom Resolution [up to 12 months]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with relapsed or refractory Hodgkin lymphoma who have previously received autologous stem cell transplant.

• Histologically confirmed CD30-positive disease; tissue from the most recent post diagnostic biopsy of relapsed/refractory disease must be available for confirmation of CD30 expression via slides or tumor block.

• Fluorodeoxyglucose-avid disease by positron emission tomography and measurable disease of at least 1.5 cm as documented by spiral computed tomography.

• At US sites patients greater than or equal to 12 years of age may be enrolled. At non-US sites patients must be greater than or equal to 18 years of age.

Exclusion Criteria:

• Previous treatment with brentuximab vedotin.

• Previously received an allogeneic transplant.

• Congestive heart failure, Class III or IV, by the New York Heart Association criteria.

• History of another primary malignancy that has not been in remission for at least 3 years.

• Known cerebral/meningeal disease.

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	91010-3000
3	University of California at Los Angeles	Los Angeles	California	United States	90095
4	Stanford University Medical Center	Palo Alto	California	United States	94305
5	Rocky Mountain Cancer Center	Denver	Colorado	United States	80218
6	Georgetown University	Washington	District of Columbia	United States	20007
7	University of Miami	Miami	Florida	United States	33136
8	Loyola University Medical Center Cardinal Bernardin Cancer Center	Maywood	Illinois	United States	60153
9	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
10	Mayo Clinic Rochester	Rochester	Minnesota	United States	55905
11	Washington University School of Medicine	St. Louis	Missouri	United States	63110
12	Weill Cornell Medical College	New York	New York	United States	10021
13	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
14	University of Rochester Medical Center	Rochester	New York	United States	14642
15	Ohio State University	Columbus	Ohio	United States	43210
16	Oregon Health & Science University	Portland	Oregon	United States	97239
17	Baylor Sammons Cancer Center	Dallas	Texas	United States	75246
18	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030-4009
19	University of Washington	Seattle	Washington	United States	98109
20	UZ Gasthuisberg	Leuven		Belgium	3000
21	Cliniques Universitaires UCL de Mont-Goddine	Yvoir		Belgium	5530
22	B.C Cancer Agency	Vancouver	British Columbia	Canada	V5Z 4E6
23	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
24	Institut Paoli Calmettes	Marseille		France	13273
25	Hospital Saint Louis	Paris		France	75475
26	Centre Henri Becquerel	Rouen		France	76038
27	Instituto di Ematologia ed Oncologia Medica	Bologna		Italy	40138

Sponsors and Collaborators

• Seagen Inc.
• Millennium Pharmaceuticals, Inc.

Investigators

• Study Director: Abraham Fong, MD, PhD, Seagen Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Seagen Inc.
• ClinicalTrials.gov Identifier: NCT00848926
• Other Study ID Numbers: SG035-0003; 2008-006034-10
• First Posted: Feb 20, 2009
• Last Update Posted: Mar 13, 2017
• Last Verified: Jun 1, 2015

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

Study Results

Participant Flow

Recruitment Details	Enrollment period: Feb 2009 - Aug 2009

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by intravenous (IV) infusion
Period Title: Treatment Period
STARTED	102
COMPLETED	18
NOT COMPLETED	84
Period Title: Treatment Period
STARTED	102
COMPLETED	90
NOT COMPLETED	12

Baseline Characteristics

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Overall Participants	102
Age, Customized (years) [Median (Full Range) ]
Median (Full Range) [years]	31.0
Sex: Female, Male (Count of Participants)
Female	54 52.9%
Male	48 47.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	7 6.9%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 4.9%
White	89 87.3%
More than one race	0 0%
Unknown or Not Reported	1 1%
Eastern Cooperative Oncology Group Performance Status (participants) [Number]
0	42 41.2%
1	60 58.8%
2-5	0 0%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate by Independent Review Group
Description	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.
Time Frame	up to 12 months

Outcome Measure Data

Analysis Population Description

Intention to treat

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Measure Participants	102
Number (95% Confidence Interval) [percent of participants]	75 73.5%

2. Secondary Outcome

Title	Complete Remission Rate by Independent Review Group
Description	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.
Time Frame	up to 12 months

Outcome Measure Data

Analysis Population Description

Intention to treat

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Measure Participants	102
Number (95% Confidence Interval) [percent of participants]	33 32.4%

3. Secondary Outcome

Title	Duration of Objective Response by Kaplan-Meier Analysis
Description	Duration of objective response (CR + PR) by independent review group, defined as time of initial response until disease progression or death.
Time Frame	up to approximately 4 years

Outcome Measure Data

Analysis Population Description

Participants with objective response among the intention to treat population

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Measure Participants	76
Median (95% Confidence Interval) [months]	6.7

4. Secondary Outcome

Title	Duration of Objective Response in Participants With Complete Remission by Kaplan-Meier Analysis
Description	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.
Time Frame	up to approximately 4 years

Outcome Measure Data

Analysis Population Description

Participants with complete remission among the intention to treat population

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Measure Participants	34
Median (95% Confidence Interval) [months]	27.9

5. Secondary Outcome

Title	Progression-free Survival by Kaplan-Meier Analysis
Description	Time from start of study treatment to disease progression per independent review group or death due to any cause.
Time Frame	up to approximately 4 years

Outcome Measure Data

Analysis Population Description

Intention to treat

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Measure Participants	102
Median (95% Confidence Interval) [months]	5.6

6. Secondary Outcome

Title	Overall Survival
Description	Time from start of study treatment to date of death due to any cause.
Time Frame	up to approximately 6 years

Outcome Measure Data

Analysis Population Description

Intention to treat

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Measure Participants	102
Median (95% Confidence Interval) [months]	40.5

7. Secondary 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). 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 12 months

Outcome Measure Data

Analysis Population Description

All participants who received treatment

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Measure Participants	102
Any TEAE	100 98%
TEAE related to study drug	94 92.2%
TEAE with severity grade >/=3	56 54.9%
Serious adverse event	25 24.5%
Serious adverse event related to study drug	14 13.7%
Discontinued treatment due to adverse event	20 19.6%

8. Secondary Outcome

Title	Hematology Laboratory Abnormalities >/= Grade 3
Description	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.
Time Frame	up to 12 months

Outcome Measure Data

Analysis Population Description

All participants who received treatment

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Measure Participants	102
Any >/= Grade 3 hematology laboratory abnormality	35 34.3%
Hemoglobin (low)	7 6.9%
Leukocytes (low)	6 5.9%
Lymphocytes (low)	20 19.6%
Neutrophils (low)	12 11.8%
Platelets (low)	7 6.9%

9. Secondary Outcome

Title	Chemistry Laboratory Abnormalities >/= Grade 3
Description	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.
Time Frame	up to 12 months

Outcome Measure Data

Analysis Population Description

All participants who received treatment

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Measure Participants	102
Any >/= Grade 3 chemistry laboratory abnormality	14 13.7%
Alanine aminotransferase (high)	1 1%
Albumin (low)	1 1%
Calcium (low)	1 1%
Glucose (high)	7 6.9%
Potassium (low)	2 2%
Sodium (high)	1 1%
Urate (high)	1 1%

10. Secondary Outcome

Title	Area Under the Curve
Description	Area under the serum concentration-time curve from time 0 to 21 days following the first dose of brentuximab vedotin
Time Frame	3 weeks

Outcome Measure Data

Analysis Population Description

All participants who received treatment

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Measure Participants	102
Geometric Mean (Geometric Coefficient of Variation) [day * microgram/mL]	88 (46)

11. Other Pre-specified Outcome

Title	B Symptom Resolution
Description	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.
Time Frame	up to 12 months

Outcome Measure Data

Analysis Population Description

Participants with B symptoms at baseline

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Measure Participants	35
Number (95% Confidence Interval) [percent of participants]	77 75.5%

12. Secondary Outcome

Title	Maximum Serum Concentration
Description	Maximum serum concentration from 0 to 21 days following the first dose of brentuximab vedotin
Time Frame	3 weeks

Outcome Measure Data

Analysis Population Description

All participants who received treatment

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Measure Participants	102
Geometric Mean (Geometric Coefficient of Variation) [microgram/mL]	35 (17)

13. Secondary Outcome

Title	Time of Maximum Serum Concentration
Description	Time of maximum serum concentration from 0 to 21 days following the first dose of brentuximab vedotin
Time Frame	3 weeks

Outcome Measure Data

Analysis Population Description

All participants who received treatment

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Measure Participants	102
Median (Full Range) [days]	0.02

Adverse Events

Time Frame	Treatment-emergent adverse events through 30 days after last dose (up to 12 months)
Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
All Cause Mortality
	Brentuximab Vedotin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Brentuximab Vedotin
	Affected / at Risk (%)	# Events
Total	25/102 (24.5%)
Blood and lymphatic system disorders
Thrombocytopenia	1/102 (1%)
Gastrointestinal disorders
Abdominal pain	2/102 (2%)
Abdominal pain upper	1/102 (1%)
Diarrhoea	1/102 (1%)
Gastrointestinal haemorrhage	1/102 (1%)
Haematemesis	1/102 (1%)
Intestinal perforation	1/102 (1%)
Nausea	1/102 (1%)
General disorders
Pyrexia	2/102 (2%)
Infections and infestations
Bronchitis	1/102 (1%)
Candidiasis	1/102 (1%)
Cellulitis	1/102 (1%)
H1N1 influenza	1/102 (1%)
Lung infection	1/102 (1%)
Pneumocystis jiroveci pneumonia	1/102 (1%)
Pneumonia	1/102 (1%)
Pyelonephritis	2/102 (2%)
Septic shock	1/102 (1%)
Soft tissue infection	1/102 (1%)
Staphylococcal bacteraemia	1/102 (1%)
Urinary tract infection staphylococcal	1/102 (1%)
Injury, poisoning and procedural complications
Wrist fracture	1/102 (1%)
Metabolism and nutrition disorders
Hyperglycaemia	1/102 (1%)
Musculoskeletal and connective tissue disorders
Flank pain	1/102 (1%)
Muscular weakness	1/102 (1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Diffuse large B-cell lymphoma	1/102 (1%)
Hodgkin's disease recurrent	1/102 (1%)
Nervous system disorders
Demyelinating polyneuropathy	2/102 (2%)
Diabetic coma	1/102 (1%)
Peripheral motor neuropathy	1/102 (1%)
Psychiatric disorders
Mental status changes	1/102 (1%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis	1/102 (1%)
Pleural effusion	1/102 (1%)
Pneumonitis	2/102 (2%)
Pneumothorax	2/102 (2%)
Pulmonary embolism	2/102 (2%)
Skin and subcutaneous tissue disorders
Stevens-Johnson syndrome	1/102 (1%)
Other (Not Including Serious) Adverse Events
	Brentuximab Vedotin
	Affected / at Risk (%)	# Events
Total	97/102 (95.1%)
Blood and lymphatic system disorders
Anaemia	9/102 (8.8%)
Lymphadenopathy	11/102 (10.8%)
Neutropenia	22/102 (21.6%)
Thrombocytopenia	7/102 (6.9%)
Gastrointestinal disorders
Abdominal pain	15/102 (14.7%)
Constipation	16/102 (15.7%)
Diarrhoea	37/102 (36.3%)
Nausea	43/102 (42.2%)
Vomiting	22/102 (21.6%)
General disorders
Chills	13/102 (12.7%)
Fatigue	47/102 (46.1%)
Pain	7/102 (6.9%)
Pyrexia	30/102 (29.4%)
Infections and infestations
Bronchitis	8/102 (7.8%)
Herpes zoster	7/102 (6.9%)
Sinusitis	9/102 (8.8%)
Upper respiratory tract infection	38/102 (37.3%)
Urinary tract infection	6/102 (5.9%)
Investigations
Weight decrease	6/102 (5.9%)
Metabolism and nutrition disorders
Decreased appetite	11/102 (10.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	19/102 (18.6%)
Back pain	14/102 (13.7%)
Bone pain	8/102 (7.8%)
Muscle spasms	9/102 (8.8%)
Myalgia	17/102 (16.7%)
Neck pain	6/102 (5.9%)
Pain in extremity	10/102 (9.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hodgkin's disease recurrent	6/102 (5.9%)
Nervous system disorders
Dizziness	11/102 (10.8%)
Headache	19/102 (18.6%)
Peripheral motor neuropathy	11/102 (10.8%)
Peripheral sensory neuropathy	48/102 (47.1%)
Psychiatric disorders
Anxiety	11/102 (10.8%)
Depression	8/102 (7.8%)
Insomnia	14/102 (13.7%)
Respiratory, thoracic and mediastinal disorders
Cough	21/102 (20.6%)
Dyspnoea	13/102 (12.7%)
Nasal congestion	6/102 (5.9%)
Oropharyngeal pain	11/102 (10.8%)
Productive cough	6/102 (5.9%)
Skin and subcutaneous tissue disorders
Alopecia	13/102 (12.7%)
Hyperhidrosis	6/102 (5.9%)
Night sweats	12/102 (11.8%)
Pruritus	16/102 (15.7%)
Rash	14/102 (13.7%)

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 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.