Brentuximab Vedotin Plus AVD in Limited-stage Hodgkin Lymphoma

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01534078
• Collaborator: Beth Israel Deaconess Medical Center (Other), Dana-Farber Cancer Institute (Other), H. Lee Moffitt Cancer Center and Research Institute (Other), Seagen Inc. (Industry)
• Enrollment: 34
• Locations: 4
• Arm: 1
• Actual Duration (Months): 70
• Patients Per Site: 8.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Brentuximab is an antibody-drug conjugate (ADC), which is the combination of an antibody (a protein that binds to cells) and a chemotherapy molecule. Brentuximab works by using the antibody portion to enter into the Hodgkin lymphoma cells and then releasing the chemotherapy portion, which attempts to destroy the cell.

The intravenous chemotherapy drugs Adriamycin, Vinblastine and Dacarbazine (AVD) which you will receive in this research study are approved for use in people with Hodgkin Lymphoma. A drug called bleomycin is usually included with AVD, but since it appears to be a less effective drug with significant potential risks, it is being replaced in this study with the drug brentuximab.

In this research study, the investigators are looking to see whether brentuximab in combination with AVD is effective in treating limited-stage Hodgkin Lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Hodgkin Lymphoma	Drug: Brentuximab Vedotin; Drug: Adriamycin, vinblastine, and dacarbazine	Phase 2

Detailed Description

Each treatment cycle is 28 days. You will receive brentuximab alone on Day 1 and 15 of the first cycle (lead-in cycle). After cycle 1, you will receive brentuximab combined with AVD on Day 1 and 15 for 4-6 cycles, depending on your response to therapy. Brentuximab and AVD will be given to you by intravenous infusion (IV).

The following test and procedures will be performed on Days 1 and 15 of each cycle:

• Review of any side effects you have experienced and all medications you are taking

• Performance Status

• Physical exam and vital signs

• Routine blood tests

• Questionnaire to evaluate symptoms of neuropathy

• Research blood sample to look at markers to see how your body is responding to study medication

• PET-CT scan prior to completing cycle 2 of combination brentuximab/AVD

After the final dose of the study drug: The following assessments will be performed within one month of your last dose of study medication:

• Review of any side effects you have experienced and all medications you are taking

• Performance Status

• Physical exam and vital signs

• Routine blood tests

• Questionnaire to evaluate symptoms of neuropathy

• Research blood sample to look at markers to see how your body is responding to study medication

• PET-CT scan Follow up will include the following

• Review of any side effects you have experienced and all medications you are taking

• Performance Status

• Review and Physical exam

• Routine blood tests

• Questionnaire to evaluate symptoms of neuropathy

• CT scans

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Brentuximab Vedotin Plus AVD in Non-bulky Limited Stage Hodgkin Lymphoma
• Actual Study Start Date: Mar 1, 2012
• Actual Primary Completion Date: Jan 1, 2015
• Actual Study Completion Date: Jan 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Arm Brentuximab Vedotin in combination with Adriamycin, Vinblastine and Dacarbazine	Drug: Brentuximab Vedotin; 2 doses administered 14 days apart; followed by combination therapy with AVD for 4-6 cycles; 1.2 mg/kg; Other Names: Adcetris SGN-35 SGN35 ; Drug: Adriamycin, vinblastine, and dacarbazine; Combination therapy with brentuximab for 4-6 cycles; 25 mg/m2 Adriamycin; 6 mg/m2 Vinblastine; 375 mg/m2 Dacarbazine; Other Names: Doxorubicin Velban DTIC

Outcome Measures

Primary Outcome Measures

1. Complete Response Rate [End of Therapy (median duration of four months)]

   Complete response rate at the end of therapy as measured by Positron emission tomography-computed tomography (PET/CT). Response is evaluated using Revised International Working Group Criteria. Complete response is defined as disappearance of all evidence of disease.

Secondary Outcome Measures

1. Overall Response Rate After One Cycle of Brentuximab [28 days]

   The number of participants achieving a Partial Response (PR) or Complete Response (CR) after one cycle of Brentuximab monotherapy as measured via PET/CT response. Response is evaluated using the Revised International Working Group Criteria. CR: Disappearance of all evidence of disease PR: Regression of measurable disease and no new sites

2. Overall Response Rate [End of Therapy (median duration of four months)]

   The number of participants achieving a Partial Response (PR) or Complete Response (CR) at the end of therapy as measured via PET/CT response. Response is evaluated using the Revised International Working Group Criteria. CR: Disappearance of all evidence of disease PR: Regression of measurable disease and no new sites

3. Grade III or IV Adverse Events [2 years]

   A summary of the grade 3 or 4 adverse events experienced by participants as determined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The data is shown as the number of participants that experienced at least one grade 3 or 4 adverse event for each of the specified toxicities.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Previously untreated stage IA, IB, IIA or IIB classical Hodgkin Lymphoma

• Non-bulky disease defined as less than 10 cm in maximal diameter

• Measurable disease greater than or equal to 1.5 cm

• ECOG performance status of 0 or 2

• Willing to use 2 effective forms of birth control

Exclusion Criteria:

• No prior chemotherapy or radiotherapy for Hodgkin lymphoma

• Not receiving any other investigational agents

• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to Adriamycin, Vinblastine, Dacarbazine or brentuximab

• No pre-existing grade 3 or greater neuropathy

• No uncontrolled intercurrent illness

• Not pregnant or breastfeeding

• No history of a different malignancy unless disease free for at least one year

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Moffitt Cancer Center	Tampa	Florida	United States	33612
2	Massachusetts General Hosptial	Boston	Massachusetts	United States	02114
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
4	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Massachusetts General Hospital
• Beth Israel Deaconess Medical Center
• Dana-Farber Cancer Institute
• H. Lee Moffitt Cancer Center and Research Institute
• Seagen Inc.

Investigators

• Principal Investigator: Jeremy Abramson, M.D., Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jeremy Abramson, MD, Principal Investigator, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01534078
• Other Study ID Numbers: 11-462
• First Posted: Feb 16, 2012
• Last Update Posted: Feb 20, 2018
• Last Verified: Jan 1, 2018

• Keywords provided by Jeremy Abramson, MD, Principal Investigator, Massachusetts General Hospital: non-bulky; limited stage
• Additional relevant MeSH terms: Lymphoma; Hodgkin Disease; Doxorubicin; Liposomal doxorubicin; Brentuximab Vedotin; Dacarbazine; Vinblastine

Study Results

Participant Flow

Arm/Group Title	Treatment Arm
Arm/Group Description	Brentuximab Vedotin in combination with Adriamycin, Vinblastine and Dacarbazine (AVD) Brentuximab Vedotin: 2 doses administered 14 days apart; followed by combination therapy with AVD for 4-6 cycles; 1.2 mg/kg Adriamycin, vinblastine, and dacarbazine: Combination therapy with brentuximab for 4-6 cycles; 25 mg/m2 Adriamycin; 6 mg/m2 Vinblastine; 375 mg/m2 Dacarbazine
Period Title: Overall Study
STARTED	34
COMPLETED	32
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Treatment Arm
Arm/Group Description	Brentuximab Vedotin in combination with Adriamycin, Vinblastine and Dacarbazine Brentuximab Vedotin: 2 doses administered 14 days apart; followed by combination therapy with AVD for 4-6 cycles; 1.2 mg/kg Adriamycin, vinblastine, and dacarbazine: Combination therapy with brentuximab for 4-6 cycles; 25 mg/m2 Adriamycin; 6 mg/m2 Vinblastine; 375 mg/m2 Dacarbazine
Overall Participants	34
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	36
Age, Customized (Count of Participants)
20 - 30 years	10 29.4%
31 - 40 years	9 26.5%
41 - 60 years	10 29.4%
61 - 75 years	5 14.7%
Sex: Female, Male (Count of Participants)
Female	17 50%
Male	17 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	26 76.5%
Unknown or Not Reported	8 23.5%
Race/Ethnicity, Customized (Count of Participants)
More Than One Race	1 2.9%
Other	7 20.6%
White	26 76.5%
Region of Enrollment (participants) [Number]
United States	34 100%
Stage (Count of Participants)
IA	6 17.6%
IIA	24 70.6%
IIB	4 11.8%
Cellularity (Count of Participants)
Hypercellular	1 2.9%
Hypocellular	4 11.8%
Normocellular	10 29.4%
Missing	19 55.9%
Histology (Count of Participants)
Classical Hodgkin Lymphoma, NOS	8 23.5%
Lymphocytic Rich	4 11.8%
Mixed Cellularity	4 11.8%
Nodular Sclerosis	18 52.9%
Risk Class (Count of Participants)
Early Favorable	21 61.8%
Early Unfavorable	13 38.2%
Number of Lesions (Lesions) [Median (Full Range) ]
Median (Full Range) [Lesions]	5
Longest Tumor Diameter (Centimeters (cm)) [Median (Full Range) ]
Median (Full Range) [Centimeters (cm)]	33.4

Outcome Measures

1. Primary Outcome

Title	Complete Response Rate
Description	Complete response rate at the end of therapy as measured by Positron emission tomography-computed tomography (PET/CT). Response is evaluated using Revised International Working Group Criteria. Complete response is defined as disappearance of all evidence of disease.
Time Frame	End of Therapy (median duration of four months)

Outcome Measure Data

Analysis Population Description

Two participants were not evaluated for response due to a death and a withdrawal.

Arm/Group Title	Treatment Arm
Arm/Group Description	Brentuximab Vedotin in combination with Adriamycin, Vinblastine and Dacarbazine Brentuximab Vedotin: 2 doses administered 14 days apart; followed by combination therapy with AVD for 4-6 cycles; 1.2 mg/kg Adriamycin, vinblastine, and dacarbazine: Combination therapy with brentuximab for 4-6 cycles; 25 mg/m2 Adriamycin; 6 mg/m2 Vinblastine; 375 mg/m2 Dacarbazine
Measure Participants	32
Count of Participants [Participants]	31 91.2%

2. Secondary Outcome

Title	Overall Response Rate After One Cycle of Brentuximab
Description	The number of participants achieving a Partial Response (PR) or Complete Response (CR) after one cycle of Brentuximab monotherapy as measured via PET/CT response. Response is evaluated using the Revised International Working Group Criteria. CR: Disappearance of all evidence of disease PR: Regression of measurable disease and no new sites
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Arm
Arm/Group Description	Brentuximab Vedotin in combination with Adriamycin, Vinblastine and Dacarbazine Brentuximab Vedotin: 2 doses administered 14 days apart; followed by combination therapy with AVD for 4-6 cycles; 1.2 mg/kg Adriamycin, vinblastine, and dacarbazine: Combination therapy with brentuximab for 4-6 cycles; 25 mg/m2 Adriamycin; 6 mg/m2 Vinblastine; 375 mg/m2 Dacarbazine
Measure Participants	34
Count of Participants [Participants]	18 52.9%

3. Secondary Outcome

Title	Overall Response Rate
Description	The number of participants achieving a Partial Response (PR) or Complete Response (CR) at the end of therapy as measured via PET/CT response. Response is evaluated using the Revised International Working Group Criteria. CR: Disappearance of all evidence of disease PR: Regression of measurable disease and no new sites
Time Frame	End of Therapy (median duration of four months)

Outcome Measure Data

Analysis Population Description

Two participants were not evaluated for response due to a death and a withdrawal.

Arm/Group Title	Treatment Arm
Arm/Group Description	Brentuximab Vedotin in combination with Adriamycin, Vinblastine and Dacarbazine Brentuximab Vedotin: 2 doses administered 14 days apart; followed by combination therapy with AVD for 4-6 cycles; 1.2 mg/kg Adriamycin, vinblastine, and dacarbazine: Combination therapy with brentuximab for 4-6 cycles; 25 mg/m2 Adriamycin; 6 mg/m2 Vinblastine; 375 mg/m2 Dacarbazine
Measure Participants	32
Complete Response	31 91.2%
Partial Response	0 0%

4. Secondary Outcome

Title	Grade III or IV Adverse Events
Description	A summary of the grade 3 or 4 adverse events experienced by participants as determined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The data is shown as the number of participants that experienced at least one grade 3 or 4 adverse event for each of the specified toxicities.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Arm
Arm/Group Description	Brentuximab Vedotin in combination with Adriamycin, Vinblastine and Dacarbazine Brentuximab Vedotin: 2 doses administered 14 days apart; followed by combination therapy with AVD for 4-6 cycles; 1.2 mg/kg Adriamycin, vinblastine, and dacarbazine: Combination therapy with brentuximab for 4-6 cycles; 25 mg/m2 Adriamycin; 6 mg/m2 Vinblastine; 375 mg/m2 Dacarbazine
Measure Participants	34
Peripheral sensory neuropathy	8 23.5%
Neutrophil count decreased	21 61.8%
Fatigue	3 8.8%
Nausea	1 2.9%
Anemia	2 5.9%
White blood cell decreased	6 17.6%
Abdominal pain	2 5.9%
Diarrhea	1 2.9%
Febrile neutropenia	12 35.3%
Vomiting	1 2.9%
Mucositis oral	1 2.9%
Weight loss	2 5.9%
Dehydration	1 2.9%
Hypertension	1 2.9%
Infections and infestations - Other, specify	1 2.9%
Blood and lymphatic system disorders - Other, spec	1 2.9%

Adverse Events

Time Frame	From the start of therapy until the the end of followup due to disease progression, death, or withdrawal from the study. Median follow-up duration of 38 months.
Adverse Event Reporting Description	Adverse events were assessed with regularly scheduled physical exams, laboratory tests, and participant self reports.
Arm/Group Title	Treatment Arm
Arm/Group Description	Brentuximab Vedotin in combination with Adriamycin, Vinblastine and Dacarbazine Brentuximab Vedotin: 2 doses administered 14 days apart; followed by combination therapy with AVD for 4-6 cycles; 1.2 mg/kg Adriamycin, vinblastine, and dacarbazine: Combination therapy with brentuximab for 4-6 cycles; 25 mg/m2 Adriamycin; 6 mg/m2 Vinblastine; 375 mg/m2 Dacarbazine
All Cause Mortality
	Treatment Arm
	Affected / at Risk (%)	# Events
Total	1/34 (2.9%)
Serious Adverse Events
	Treatment Arm
	Affected / at Risk (%)	# Events
Total	15/34 (44.1%)
Blood and lymphatic system disorders
Febrile Neutropenia	8/34 (23.5%)	8
Cardiac disorders
Chest Pain - Cardiac	1/34 (2.9%)	1
Gastrointestinal disorders
Viral Gastritis	1/34 (2.9%)	1
Abdominal Pain	2/34 (5.9%)	2
Gastric Hemorrhage	1/34 (2.9%)	1
Ileus	1/34 (2.9%)	1
Nausea, Vomiting, Dehydration	1/34 (2.9%)	1
Anorexia, Nausea, Vomiting	1/34 (2.9%)	1
Diarrhea, Hypotension	1/34 (2.9%)	1
Ileus, Esophagitis, Transaminase elevation, low white blood cell count, dehydration	1/34 (2.9%)	1
General disorders
Fever	1/34 (2.9%)	1
Fever, Sinus Congestion	1/34 (2.9%)	1
Infections and infestations
Sepsis	1/34 (2.9%)	1
Bronchial Infection	1/34 (2.9%)	1
Line Infection	1/34 (2.9%)	1
Soft Tissue Infection	1/34 (2.9%)	1
Investigations
Neutrophil Count Decreased	2/34 (5.9%)	2
White Blood Cell Decreased	1/34 (2.9%)	2
Metabolism and nutrition disorders
Dehydration	1/34 (2.9%)	1
Anorexia, Fatigue	1/34 (2.9%)	1
Musculoskeletal and connective tissue disorders
Hip pain, back pain	1/34 (2.9%)	1
Psychiatric disorders
Confusion	1/34 (2.9%)	1
Respiratory, thoracic and mediastinal disorders
Aspiration	1/34 (2.9%)	1
Skin and subcutaneous tissue disorders
Hidradenitis Suppurativa	1/34 (2.9%)	1
Other (Not Including Serious) Adverse Events
	Treatment Arm
	Affected / at Risk (%)	# Events
Total	34/34 (100%)
Blood and lymphatic system disorders
Anemia	27/34 (79.4%)	52
Febrile neutropenia	6/34 (17.6%)	6
Leukocytosis	3/34 (8.8%)	5
Cardiac disorders
Sinus tachycardia	2/34 (5.9%)	4
Ear and labyrinth disorders
Tinnitus	5/34 (14.7%)	5
Endocrine disorders
Endocrine disorders - Other, specify	2/34 (5.9%)	2
Gastrointestinal disorders
Abdominal pain	14/34 (41.2%)	24
Bloating	2/34 (5.9%)	2
Colitis	2/34 (5.9%)	2
Constipation	26/34 (76.5%)	35
Diarrhea	15/34 (44.1%)	25
Dry mouth	2/34 (5.9%)	2
Gastritis	2/34 (5.9%)	2
Gastroesophageal reflux disease	7/34 (20.6%)	8
Hemorrhoids	4/34 (11.8%)	4
Mucositis oral	8/34 (23.5%)	8
Nausea	26/34 (76.5%)	41
Oral pain	4/34 (11.8%)	4
Rectal hemorrhage	2/34 (5.9%)	2
Vomiting	12/34 (35.3%)	18
Gastrointestinal disorders - Other, specify	5/34 (14.7%)	8
General disorders
Edema limbs	2/34 (5.9%)	2
Fatigue	30/34 (88.2%)	53
Fever	4/34 (11.8%)	6
Infusion related reaction	3/34 (8.8%)	5
Malaise	2/34 (5.9%)	2
Pain	8/34 (23.5%)	14
General disorders and administration site conditions - Other,	3/34 (8.8%)	4
Infections and infestations
Upper respiratory infection	5/34 (14.7%)	7
Urinary tract infection	2/34 (5.9%)	2
Infections and infestations - Other, specify	4/34 (11.8%)	6
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications - Other, specify	2/34 (5.9%)	2
Investigations
Alanine aminotransferase increased	14/34 (41.2%)	21
Alkaline phosphatase increased	2/34 (5.9%)	3
Aspartate aminotransferase increased	10/34 (29.4%)	14
Neutrophil count decreased	26/34 (76.5%)	74
Platelet count decreased	6/34 (17.6%)	10
Weight loss	7/34 (20.6%)	14
White blood cell decreased	21/34 (61.8%)	56
Investigations - Other, specify	2/34 (5.9%)	2
Metabolism and nutrition disorders
Anorexia	9/34 (26.5%)	11
Dehydration	5/34 (14.7%)	7
Hyperglycemia	14/34 (41.2%)	17
Hypokalemia	3/34 (8.8%)	3
Musculoskeletal and connective tissue disorders
Arthralgia	9/34 (26.5%)	12
Back pain	7/34 (20.6%)	7
Bone pain	14/34 (41.2%)	21
Generalized muscle weakness	6/34 (17.6%)	6
Myalgia	6/34 (17.6%)	8
Pain in extremity	5/34 (14.7%)	8
Musculoskeletal and connective tissue disorder -	9/34 (26.5%)	13
Nervous system disorders
Dizziness	9/34 (26.5%)	9
Headache	9/34 (26.5%)	10
Memory impairment	2/34 (5.9%)	2
Peripheral motor neuropathy	7/34 (20.6%)	11
Peripheral sensory neuropathy	27/34 (79.4%)	67
Nervous system disorders - Other, specify	3/34 (8.8%)	5
Psychiatric disorders
Anxiety	7/34 (20.6%)	8
Depression	4/34 (11.8%)	4
Insomnia	12/34 (35.3%)	14
Restlessness	2/34 (5.9%)	2
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	2/34 (5.9%)	2
Cough	8/34 (23.5%)	11
Dyspnea	5/34 (14.7%)	5
Nasal congestion	2/34 (5.9%)	2
Sore throat	3/34 (8.8%)	3
Respiratory, thoracic and mediastinal disorders - Other, specify	4/34 (11.8%)	4
Skin and subcutaneous tissue disorders
Alopecia	16/34 (47.1%)	21
Erythema multiforme	2/34 (5.9%)	3
Hyperhidrosis	6/34 (17.6%)	6
Pruritus	7/34 (20.6%)	8
Rash acneiform	5/34 (14.7%)	6
Rash maculo-papular	8/34 (23.5%)	9
Skin hyperpigmentation	2/34 (5.9%)	2
Skin and subcutaneous tissue disorders - Other, specify	8/34 (23.5%)	12
Vascular disorders
Flushing	2/34 (5.9%)	2
Hot flashes	3/34 (8.8%)	3
Hypertension	12/34 (35.3%)	31
Hypotension	2/34 (5.9%)	3
Thromboembolic event	2/34 (5.9%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT 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.