Induction Chemo w/ABVD Followed by Brentuximab Vedotin Consolidation in Newly Diagnosed, Non-Bulky Stage I/II Hodgkin Lymphoma

• Sponsor: UNC Lineberger Comprehensive Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01578967
• Collaborator: Seagen Inc. (Industry)
• Enrollment: 41
• Locations: 6
• Arm: 1
• Duration (Months): 104.3
• Patients Per Site: 6.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The standard chemotherapy for Hodgkin lymphoma is called ABVD which is a combination of 4 chemotherapy drugs (doxorubicin, bleomycin, vinblastine, and dacarbazine). The number of cycles of ABVD chemotherapy Hodgkin lymphoma patients receive is about 4-6 cycles. In addition to the ABVD chemotherapy, patients with Hodgkin lymphoma will routinely receive radiation therapy. The use of chemotherapy and radiation may cause long term treatment related side effects such as heart problems and other cancers. Researchers are trying to find if combining ABVD chemotherapy with new drugs and reducing the number of ABVD chemotherapy cycles given is just as effective as the standard Hodgkin treatment.

Brentuximab vedotin is approved by the United States Food and Drug administration (FDA) for the treatment of Hodgkin lymphoma that has come back (relapsed). For this research study, the use of brentuximab vedotin in newly diagnosed Hodgkin lymphoma is considered investigational. Brentuximab vedotin is an antibody that also has a chemotherapy drug attached to it. Antibodies are proteins that are part of your immune system. They can stick to and attack specific targets on cells. The antibody part of the brentuximab vedotin sticks to a target called cluster of differentiation antigen 30 (CD30). CD30 is an important molecule on some cancer cells and some normal cells of the immune system.

The purpose of this research study is to see the effects of treatment with fewer cycles of the combination chemotherapy, ABVD, followed by the study drug brentuximab vedotin has on study participants and Hodgkins lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Hodgkin Lymphoma, Adult	Drug: Brentuximab vedotin; Drug: ABVD	N/A

Detailed Description

This study is designed as a single arm pilot feasibility trial using an induction of 2-6 cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy followed by 6 cycles of brentuximab vedotin (SGN-35) consolidation for previously untreated patients with stage I and II non-bulky Hodgkin Lymphoma (HL).

Feasibility will be determined by the percentage of patients who have no clinical evidence of HL, and achieve positron emission tomograph (PET) negative disease post brentuximab consolidation. We anticipate approximately 40 patients will be eligible across participating centers (including UNC, Mayo Clinic, and the UNC Cancer Network (UNCCN)) over a 2 year period. A future phase II study evaluating progression free survival (PFS) after ABVD followed by brentuximab vedotin will be considered feasible if ≥ 13 of 15 patients enrolled in this pilot trial become PET negative after brentuximab vedotin consolidation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: LCCC 1115: A Pilot Feasibility Trial of Induction Chemotherapy With ABVD Followed by Brentuximab Vedotin (SGN-35) Consolidation in Patients With Previously Untreated Non-Bulky Stage I or II Hodgkin Lymphoma (HL)
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Aug 10, 2016
• Actual Study Completion Date: Dec 11, 2020

Arms and Interventions

Arm

Intervention/Treatment

Other: ABVD followed by Brentuximab vedotin Single arm trial

Drug: Brentuximab vedotin; IV, 1.8mg/kg, every 3 weeks for 6 cycles.; Other Names: SGN-35 Adcetris ; Drug: ABVD; Doxorubicin - 25mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Bleomycin - 10u/m2 IV, Day 1 and 15, every 28 days, 2-6 cycles Vinblastine - 6mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Dacarbazine - 375mg/m2 IV over 30 minutes, Day 1 and 15, every 28 days, 2-6 cycles.

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients With Positron Emission Tomography (PET) Negative Disease [12 months]

   Percentage of patients who convert to PET negative disease post consolidation. This is defined by PET with Deauville <=2. The Deauville 5-point scoring system is a five-point scoring system for the Fluorodeoxyglucose (FDG) avidity of a Hodgkin's lymphoma or Non-Hodgkin's lymphoma tumor mass as seen on FDG Positron emission tomography: Score 1: No uptake above the background Score 2: Uptake ≤ mediastinum Score 3: Uptake > mediastinum but ≤ liver Score 4: Uptake moderately increased compared to the liver at any site Score 5: Uptake markedly increased compared to the liver at any site Score X: New areas of uptake unlikely to be related to lymphoma

Secondary Outcome Measures

1. Number of Participant Who Achieved a Complete Response [12 months]

   Response criteria based on the International Workshop to standardize response criteria for malignant lymphomas. Complete Response is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.

2. Conversion Rate to Complete Response. Number of Participants Who Had a Partial Response Post ABVD Who Converted to a Complete Response. [12 months]

   Conversion rate to Complete Response after brentuximab vedotin in patients with partial response at the end of ABVD therapy. Response criteria based on the International Workshop to standardize response criteria for malignant lymphomas. Complete Response is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. These nodes or masses should be selected according to all of the following: they should be clearly measurable in at least 2 perpendicular dimensions; if possible they should be from disparate regions of the body; and they should include mediastinal and retroperitoneal areas of disease whenever these sites are involved.

3. 3 Year Progression Free Survival Rate [3 years]

   Defined as the percentage of participants who did not show relapse/progression or death from any cause occurred at 3 years after the time from ABVD treatment start. Relapse/progression is measured using the Revised Response Criteria for Malignant Lymphoma and is defined as the following: appearance of any new lesion > 1.5 centimeters (cm) in any axis during or at the end of therapy; at least a 50% increase from nadir in the sum of the product of the diameters (SPD) of any previously involved nodes, or in a single involved node, or the size of other lesions; or at least a 50% increase in the longest diameter of any single previously identified node more than 1 cm in its short axis. In addition, lesions should be PET positive if observed in a typical FDG-avid lymphoma or the lesion was positron emission tomography (PET) positive before therapy

4. 3 Year Time to Progression Rate [3 years]

   Defined as the percentage of participants who did not show relapse/progression at 3 years after the time from ABVD treatment start. Relapse/progression is measured using the Revised Response Criteria for Malignant Lymphoma and is defined as the following: appearance of any new lesion > 1.5 centimeters (cm) in any axis during or at the end of therapy; at least a 50% increase from nadir in the sum of the product of the diameters (SPD) of any previously involved nodes, or in a single involved node, or the size of other lesions; or at least a 50% increase in the longest diameter of any single previously identified node more than 1 cm in its short axis. In addition, lesions should be PET positive if observed in a typical FDG-avid lymphoma or the lesion was positron emission tomography (PET) positive before therapy

5. Number of Adverse Events Attributed to Brentuximab Vedotin With a Grade 3 or Higher [12 months]

   Number of adverse events attributed to Brentuximab Vedotin with a grade 3 or higher. Toxicity assessed via the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI CTCAE) v. 4. The NCI Common Terminology Criteria for Adverse Events is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term.The higher the grade the more severe the adverse event.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Previously untreated stage I or II non-bulky Hodgkin lymphoma

• No mediastinal mass >0.33 maximum intrathoracic diameter on chest x-ray (see Appendix B)

• No adenopathy ≥7.5 cm in its largest diameter

• Measurable disease as assessed by 2 dimensional measurement by CT (>2cm or 1.5 cm if 0.5 cm slices are used, as in spiral CT scan)

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Age ≥18 years and ≤60 years of age

• Life expectancy of at least 3 months

• Adequate bone marrow function (without transfusion support within one week of screening) as demonstrated by:

• Hemoglobin ≥ 8 g/dL

• Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3

• Platelet count ≥ 75,000/mm3

• Adequate hepatic and renal function as demonstrated by:

• Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN)

• Total serum bilirubin ≤1.5 x ULN

• Serum creatinine ≤ 2.0 mg/dL

• Negative serum human chorionic gonadotropin (β-hCG) pregnancy test within 72 hours of day 1 of treatment with ABVD in women of child-bearing potential

• Females of childbearing potential, and males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 6 months following the last dose of brentuximab vedotin. Effective contraception is defined as any medically recommended method (or combination of methods) as per standard of care, including abstinence. Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy.

• Signed an institutional review board (IRB)-approved informed consent document for this protocol

Prior to Day 1 of brentuximab vedotin, patients must again meet the following inclusion criteria:

• Adequate bone marrow function (without transfusion support within one week of D1 of brentuximab vedotin) as demonstrated by:

• Hemoglobin ≥ 8 g/dL

• Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3

• Platelet count ≥ 75,000/mm3

• Adequate hepatic and renal function as demonstrated by:

• Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN)

• Total serum bilirubin ≤1.5 x ULN

• Serum creatinine ≤ 2.0 mg/dL

• Achieved at least a partial response (PR) (and not progressed) after ABVD therapy

Exclusion Criteria:

• Prior therapies for treatment of HL including involved field radiation therapy or any prior treatment for any malignancy with anthracyclines.

• Bulky disease (defined as a mass measuring > 7.5 cm or one-third the maximal diameter of the thoracic cavity)

• Known central nervous system (CNS) involvement

• Symptomatic pulmonary disease currently requiring regular medication including but not restricted to bronchodilators

• Known history of human immunodeficiency virus (HIV), hepatitis B and hepatitis C (testing is not necessary if patient does not have history of these diseases, and no risk factors for acquisition of these viruses)

• Cardiac disease with left ventricular ejection fraction of less than 45%

• Known hypersensitivity to any excipient contained in the drug formulation of brentuximab vedotin or any component of ABVD

• Medical or other condition that would represent an inappropriate risk to the patient or would likely compromise achievement of the primary study objective

• Other active malignancies with the exception of:

• Non-melanoma skin cancer

• Cervical carcinoma in situ without evidence of disease

• Prostatic intraepithelial neoplasia without evidence of prostate cancer

• Pregnant or lactating women

Prior to Day 1 of brentuximab vedotin, please verify the patient does not meet the criteria below:

• Symptomatic pulmonary disease currently requiring regular medication including but not restricted to bronchodilators

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
2	Mayo Clinic	Rochester	Minnesota	United States	55905
3	University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
4	Levine Cancer Istitute, Carolinas Health Care system	Charlotte	North Carolina	United States	28204
5	Rex Cancer Center	Raleigh	North Carolina	United States	27607
6	Vanderbilt University	Nashville	Tennessee	United States	37240

Sponsors and Collaborators

• UNC Lineberger Comprehensive Cancer Center
• Seagen Inc.

Investigators

• Principal Investigator: Thomas Shea, MD, UNC Lineberger Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• UNC Lineberger Comprehensive Cancer Center

Publications

None provided.

• Responsible Party: UNC Lineberger Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT01578967
• Other Study ID Numbers: LCCC 1115
• First Posted: Apr 17, 2012
• Last Update Posted: Dec 7, 2021
• Last Verified: Nov 1, 2021

• Keywords provided by UNC Lineberger Comprehensive Cancer Center: Hodgkin's lymphoma; Hodgkin lymphoma
• Additional relevant MeSH terms: Lymphoma; Hodgkin Disease; Brentuximab Vedotin

Study Results

Participant Flow

Arm/Group Title	ABVD Followed by Brentuximab Vedotin
Arm/Group Description	Single arm trial Brentuximab vedotin: IV, 1.8mg/kg, every 3 weeks for 6 cycles. ABVD: Doxorubicin - 25mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Bleomycin - 10u/m2 IV, Day 1 and 15, every 28 days, 2-6 cycles Vinblastine - 6mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Dacarbazine - 375mg/m2 IV over 30 minutes, Day 1 and 15, every 28 days, 2-6 cycles.
Period Title: Overall Study
STARTED	41
COMPLETED	41
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	ABVD Followed by Brentuximab Vedotin
Arm/Group Description	Single arm trial Brentuximab vedotin: IV, 1.8mg/kg, every 3 weeks for 6 cycles. ABVD: Doxorubicin - 25mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Bleomycin - 10u/m2 IV, Day 1 and 15, every 28 days, 2-6 cycles Vinblastine - 6mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Dacarbazine - 375mg/m2 IV over 30 minutes, Day 1 and 15, every 28 days, 2-6 cycles.
Overall Participants	40
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	29
Sex: Female, Male (Count of Participants)
Female	23 57.5%
Male	17 42.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 2.5%
Not Hispanic or Latino	39 97.5%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 7.5%
White	36 90%
More than one race	0 0%
Unknown or Not Reported	1 2.5%
Region of Enrollment (participants) [Number]
United States	40 100%
Stage (Count of Participants)
I	2 5%
IIA	28 70%
IIB	10 25%
Risk (Count of Participants)
Favorable	18 45%
UnFavorable	22 55%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients With Positron Emission Tomography (PET) Negative Disease
Description	Percentage of patients who convert to PET negative disease post consolidation. This is defined by PET with Deauville <=2. The Deauville 5-point scoring system is a five-point scoring system for the Fluorodeoxyglucose (FDG) avidity of a Hodgkin's lymphoma or Non-Hodgkin's lymphoma tumor mass as seen on FDG Positron emission tomography: Score 1: No uptake above the background Score 2: Uptake ≤ mediastinum Score 3: Uptake > mediastinum but ≤ liver Score 4: Uptake moderately increased compared to the liver at any site Score 5: Uptake markedly increased compared to the liver at any site Score X: New areas of uptake unlikely to be related to lymphoma
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

One patient was not evaluable due to change in diagnosis during ABVD treatment (HL --> gray zone lymphoma). There was one death due to sepsis and hepatic failure, a very rare but known complication of brentuximab vedotin. Leaving 39 evaluable patients

Arm/Group Title	ABVD Followed by Brentuximab Vedotin
Arm/Group Description	Single arm trial Brentuximab vedotin: IV, 1.8mg/kg, every 3 weeks for 6 cycles. ABVD: Doxorubicin - 25mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Bleomycin - 10u/m2 IV, Day 1 and 15, every 28 days, 2-6 cycles Vinblastine - 6mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Dacarbazine - 375mg/m2 IV over 30 minutes, Day 1 and 15, every 28 days, 2-6 cycles.
Measure Participants	39
Count of Participants [Participants]	37 92.5%

2. Secondary Outcome

Title	Number of Participant Who Achieved a Complete Response
Description	Response criteria based on the International Workshop to standardize response criteria for malignant lymphomas. Complete Response is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

One patient was not evaluable due to change in diagnosis during ABVD treatment (HL --> gray zone lymphoma). There was one death due to sepsis and hepatic failure, a very rare but known complication of brentuximab vedotin. Leaving 39 evaluable patients

Arm/Group Title	ABVD Followed by Brentuximab Vedotin
Arm/Group Description	Single arm trial Brentuximab vedotin: IV, 1.8mg/kg, every 3 weeks for 6 cycles. ABVD: Doxorubicin - 25mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Bleomycin - 10u/m2 IV, Day 1 and 15, every 28 days, 2-6 cycles Vinblastine - 6mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Dacarbazine - 375mg/m2 IV over 30 minutes, Day 1 and 15, every 28 days, 2-6 cycles.
Measure Participants	39
Count of Participants [Participants]	37 92.5%

3. Secondary Outcome

Title	Conversion Rate to Complete Response. Number of Participants Who Had a Partial Response Post ABVD Who Converted to a Complete Response.
Description	Conversion rate to Complete Response after brentuximab vedotin in patients with partial response at the end of ABVD therapy. Response criteria based on the International Workshop to standardize response criteria for malignant lymphomas. Complete Response is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. These nodes or masses should be selected according to all of the following: they should be clearly measurable in at least 2 perpendicular dimensions; if possible they should be from disparate regions of the body; and they should include mediastinal and retroperitoneal areas of disease whenever these sites are involved.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

4 subjects had a partial response (PR) (Deauville score of 3)

Arm/Group Title	ABVD Followed by Brentuximab Vedotin
Arm/Group Description	Single arm trial Brentuximab vedotin: IV, 1.8mg/kg, every 3 weeks for 6 cycles. ABVD: Doxorubicin - 25mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Bleomycin - 10u/m2 IV, Day 1 and 15, every 28 days, 2-6 cycles Vinblastine - 6mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Dacarbazine - 375mg/m2 IV over 30 minutes, Day 1 and 15, every 28 days, 2-6 cycles.
Measure Participants	4
Count of Participants [Participants]	3 7.5%

4. Secondary Outcome

Title	3 Year Progression Free Survival Rate
Description	Defined as the percentage of participants who did not show relapse/progression or death from any cause occurred at 3 years after the time from ABVD treatment start. Relapse/progression is measured using the Revised Response Criteria for Malignant Lymphoma and is defined as the following: appearance of any new lesion > 1.5 centimeters (cm) in any axis during or at the end of therapy; at least a 50% increase from nadir in the sum of the product of the diameters (SPD) of any previously involved nodes, or in a single involved node, or the size of other lesions; or at least a 50% increase in the longest diameter of any single previously identified node more than 1 cm in its short axis. In addition, lesions should be PET positive if observed in a typical FDG-avid lymphoma or the lesion was positron emission tomography (PET) positive before therapy
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ABVD Followed by Brentuximab Vedotin
Arm/Group Description	Single arm trial Brentuximab vedotin: IV, 1.8mg/kg, every 3 weeks for 6 cycles. ABVD: Doxorubicin - 25mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Bleomycin - 10u/m2 IV, Day 1 and 15, every 28 days, 2-6 cycles Vinblastine - 6mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Dacarbazine - 375mg/m2 IV over 30 minutes, Day 1 and 15, every 28 days, 2-6 cycles.
Measure Participants	40
Number (95% Confidence Interval) [percentage of patients progression free]	92

5. Secondary Outcome

Title	3 Year Time to Progression Rate
Description	Defined as the percentage of participants who did not show relapse/progression at 3 years after the time from ABVD treatment start. Relapse/progression is measured using the Revised Response Criteria for Malignant Lymphoma and is defined as the following: appearance of any new lesion > 1.5 centimeters (cm) in any axis during or at the end of therapy; at least a 50% increase from nadir in the sum of the product of the diameters (SPD) of any previously involved nodes, or in a single involved node, or the size of other lesions; or at least a 50% increase in the longest diameter of any single previously identified node more than 1 cm in its short axis. In addition, lesions should be PET positive if observed in a typical FDG-avid lymphoma or the lesion was positron emission tomography (PET) positive before therapy
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ABVD Followed by Brentuximab Vedotin
Arm/Group Description	Single arm trial Brentuximab vedotin: IV, 1.8mg/kg, every 3 weeks for 6 cycles. ABVD: Doxorubicin - 25mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Bleomycin - 10u/m2 IV, Day 1 and 15, every 28 days, 2-6 cycles Vinblastine - 6mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Dacarbazine - 375mg/m2 IV over 30 minutes, Day 1 and 15, every 28 days, 2-6 cycles.
Measure Participants	40
Number (95% Confidence Interval) [percentage of patients progression free]	92

6. Secondary Outcome

Title	Number of Adverse Events Attributed to Brentuximab Vedotin With a Grade 3 or Higher
Description	Number of adverse events attributed to Brentuximab Vedotin with a grade 3 or higher. Toxicity assessed via the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI CTCAE) v. 4. The NCI Common Terminology Criteria for Adverse Events is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term.The higher the grade the more severe the adverse event.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Please note all grade 4 or higher events were experienced by one patient. The patient developed fever and hepatic dysfunction after 1 dose of Brentuximab Vedotin (BV). Patient also developed pancreatitis and eventually died of sepsis.

Arm/Group Title	Grade 3	Grade 4	Grade 5
Arm/Group Description	Single arm trial Brentuximab vedotin: IV, 1.8mg/kg, every 3 weeks for 6 cycles. ABVD: Doxorubicin - 25mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Bleomycin - 10u/m2 IV, Day 1 and 15, every 28 days, 2-6 cycles Vinblastine - 6mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Dacarbazine - 375mg/m2 IV over 30 minutes, Day 1 and 15, every 28 days, 2-6 cycles.	Single arm trial Brentuximab vedotin: IV, 1.8mg/kg, every 3 weeks for 6 cycles. ABVD: Doxorubicin - 25mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Bleomycin - 10u/m2 IV, Day 1 and 15, every 28 days, 2-6 cycles Vinblastine - 6mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Dacarbazine - 375mg/m2 IV over 30 minutes, Day 1 and 15, every 28 days, 2-6 cycles.	Single arm trial Brentuximab vedotin: IV, 1.8mg/kg, every 3 weeks for 6 cycles. ABVD: Doxorubicin - 25mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Bleomycin - 10u/m2 IV, Day 1 and 15, every 28 days, 2-6 cycles Vinblastine - 6mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Dacarbazine - 375mg/m2 IV over 30 minutes, Day 1 and 15, every 28 days, 2-6 cycles.
Measure Participants	40	40	40
Neutropenia	3	0	0
Infections and infestations	1	0	1
Alanine aminotransferase increased	1	0	0
Anemia	1	0	0
Ascites	0	1	0
Aspartate aminotransferase increased	1	0	0
Blood bilirubin increased	0	1	0
Creatinine increased	1	0	0
Hepatic failure	0	1	0
Hyperglycemia	1	0	0
Hypophosphatemia	1	0	0
Lipase increased	0	1	0
Pancreatitis	0	1	0
Peripheral sensory neuropathy	1	0	0
Platelet count decreased	0	1	0
Pleural effusion	0	1	0
Rash maculo-papular	1	0	0
Renal and urinary disorders	0	1	0
Sepsis	0	0	1
Syncope	1	0	0
White blood cell decreased	0	1	0

Adverse Events

Time Frame	2 years
Arm/Group Title	ABVD Followed by Brentuximab Vedotin
Arm/Group Description	Single arm trial Brentuximab vedotin: IV, 1.8mg/kg, every 3 weeks for 6 cycles. ABVD: Doxorubicin - 25mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Bleomycin - 10u/m2 IV, Day 1 and 15, every 28 days, 2-6 cycles Vinblastine - 6mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Dacarbazine - 375mg/m2 IV over 30 minutes, Day 1 and 15, every 28 days, 2-6 cycles.
All Cause Mortality
	ABVD Followed by Brentuximab Vedotin
	Affected / at Risk (%)	# Events
Total	1/41 (2.4%)
Serious Adverse Events
	ABVD Followed by Brentuximab Vedotin
	Affected / at Risk (%)	# Events
Total	6/41 (14.6%)
Hepatobiliary disorders
Cholecystitis	1/41 (2.4%)
Infections and infestations
Catheter related infection	1/41 (2.4%)
Lung infection	2/41 (4.9%)
Meningitis	1/41 (2.4%)
Investigations
Alanine aminotransferase increased	1/41 (2.4%)
Aspartate aminotransferase increased	1/41 (2.4%)
Nervous system disorders
Intracranial hemorrhage	1/41 (2.4%)
Transient ischemic attacks	1/41 (2.4%)
Respiratory, thoracic and mediastinal disorders
Pulmonary edema	1/41 (2.4%)
Vascular disorders
Hypotension	1/41 (2.4%)
Other (Not Including Serious) Adverse Events
	ABVD Followed by Brentuximab Vedotin
	Affected / at Risk (%)	# Events
Total	41/41 (100%)
Blood and lymphatic system disorders
Anemia	24/41 (58.5%)
Blood And Lymphatic System Disorders - Other, Specify	3/41 (7.3%)
Cardiac disorders
Palpitations	2/40 (5%)
Eye disorders
Blurred Vision	2/41 (4.9%)
Gastrointestinal disorders
Abdominal Pain	2/41 (4.9%)
Constipation	17/41 (41.5%)
Diarrhea	13/41 (31.7%)
Dyspepsia	2/41 (4.9%)
Gastroesophageal Reflux Disease	8/41 (19.5%)
Gastrointestinal Disorders - Other, Specify	3/41 (7.3%)
Mucositis Oral	7/40 (17.5%)
Nausea	31/40 (77.5%)
Vomiting	10/40 (25%)
General disorders
Chills	9/41 (22%)
Edema Limbs	6/41 (14.6%)
Fatigue	34/41 (82.9%)
Fever	9/41 (22%)
General Disorders And Administration Site Conditions - Other, Specify	3/41 (7.3%)
Infusion Related Reaction	2/40 (5%)
Injection Site Reaction	3/40 (7.5%)
Malaise	9/40 (22.5%)
Non-Cardiac Chest Pain	3/40 (7.5%)
Pain	11/40 (27.5%)
Immune system disorders
Allergic Reaction	2/41 (4.9%)
Infections and infestations
Papulopustular Rash	2/40 (5%)
Sinusitis	2/40 (5%)
Skin Infection	5/40 (12.5%)
Upper Respiratory Infection	4/40 (10%)
Investigations
Alanine Aminotransferase Increased	18/41 (43.9%)
Alkaline Phosphatase Increased	6/41 (14.6%)
Aspartate Aminotransferase Increased	15/41 (36.6%)
Blood Bilirubin Increased	4/41 (9.8%)
Creatinine Increased	3/41 (7.3%)
Lymphocyte Count Decreased	3/40 (7.5%)
Neutrophil Count Decreased	32/40 (80%)
Platelet Count Decreased	3/40 (7.5%)
Weight Gain	5/40 (12.5%)
Weight Loss	2/40 (5%)
White Blood Cell Decreased	24/40 (60%)
Metabolism and nutrition disorders
Anorexia	11/41 (26.8%)
Hyperglycemia	14/41 (34.1%)
Hyperkalemia	2/41 (4.9%)
Hypoalbuminemia	4/41 (9.8%)
Hypocalcemia	4/40 (10%)
Hypoglycemia	2/40 (5%)
Hypokalemia	3/40 (7.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/41 (17.1%)
Back Pain	2/41 (4.9%)
Bone Pain	5/41 (12.2%)
Generalized Muscle Weakness	2/41 (4.9%)
Myalgia	8/40 (20%)
Neck Pain	2/40 (5%)
Pain In Extremity	5/40 (12.5%)
Nervous system disorders
Dizziness	4/41 (9.8%)
Headache	10/41 (24.4%)
Paresthesia	3/40 (7.5%)
Peripheral Sensory Neuropathy	31/40 (77.5%)
Syncope	2/40 (5%)
Psychiatric disorders
Anxiety	4/41 (9.8%)
Depression	3/41 (7.3%)
Insomnia	10/40 (25%)
Renal and urinary disorders
Urinary Frequency	2/40 (5%)
Urinary Tract Pain	2/40 (5%)
Respiratory, thoracic and mediastinal disorders
Allergic Rhinitis	2/41 (4.9%)
Cough	13/41 (31.7%)
Dyspnea	8/41 (19.5%)
Hiccups	2/41 (4.9%)
Hoarseness	2/41 (4.9%)
Nasal Congestion	6/40 (15%)
Postnasal Drip	3/40 (7.5%)
Sore Throat	4/40 (10%)
Wheezing	2/40 (5%)
Skin and subcutaneous tissue disorders
Alopecia	17/41 (41.5%)
Dry Skin	3/41 (7.3%)
Pruritus	9/40 (22.5%)
Rash Acneiform	6/40 (15%)
Rash Maculo-Papular	19/40 (47.5%)
Urticaria	2/40 (5%)
Vascular disorders
Hot Flashes	2/41 (4.9%)

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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.