Brentuximab Vedotin Plus AD in Non-bulky Limited Stage Hodgkin Lymphoma

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02505269
• Collaborator: Seagen Inc. (Industry)
• Enrollment: 34
• Locations: 2
• Arm: 1
• Actual Duration (Months): 45.8
• Patients Per Site: 17
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Limited stage Hodgkin lymphoma is a highly curable disease, but standard treatment with ABVD chemotherapy and radiation can lead to late risks of secondary cancers, lung injury, heart injury, and others. This trial eliminates radiation therapy and reduces intensity of chemotherapy by incorporating the highly active FDA-approved targeted therapy brentuximab vedotin, an antibody-drug conjugate specifically against the lymphoma cells, combined with the standard chemotherapy drugs Adriamycin and Dacarbazine (AD).

Condition or Disease	Intervention/Treatment	Phase
Hodgkin Lymphoma	Drug: Brentuximab Vedotin; Drug: Adriamycin; Drug: Dacarbazine	Phase 2

Detailed Description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied. It also means that the FDA (the U.S. Food and Drug Administration) has not yet approved brentuximab vedotin (brentuximab) as part of the initial treatment of Hodgkin lymphoma. Currently, brentuximab is FDA-approved for treatment of relapsed Hodgkin lymphoma.

• Brentuximab works by binding specifically to Hodgkin lymphoma cells, entering the cells, and then releasing the drug to destroy the cell.

• The chemotherapy drugs Adriamycin and Dacarbazine (AD) which which participants will receive in this research study are approved for use in people with Hodgkin Lymphoma.

• Patients will not receive planned radiation therapy, or the drugs bleomycin or vinblastine.

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 AD in Non-bulky Limited Stage Hodgkin Lymphoma
• Actual Study Start Date: Aug 7, 2015
• Actual Primary Completion Date: Jun 1, 2019
• Actual Study Completion Date: Jun 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Brentuximab Vedotin The following procedures will take place during study visits beginning after the screening procedures: - Participants will receive combination therapy: Brentuximab Vedotin intravenously on predetermined days per cycle Adriamycin intravenously on predetermined days per cycle Dacarbazine intravenously on predetermined days per cycle	Drug: Brentuximab Vedotin; Other Names: Adcetris ; Drug: Adriamycin; Other Names: Doxorubicin Rubex ® ; Drug: Dacarbazine; Other Names: DTIC-Dome® DTIC DIC Imidazole Carboxamide

Outcome Measures

Primary Outcome Measures

1. Complete Response Rate [4-6 months]

   The number of patients that achieved a complete response (CR) to therapy as assessed by the revised International Working Group Criteria. Complete response: Lymph nodes and extralymphatic sites: Score 1, 2, or 3 with or without a residual mass on 5-point (Daeuville) scale Bone Marrow: No evidence of FDG-avi disease No new lesions Deauville Criteria for PET scan Interpretation in Lymphoma Five-point scale: No Uptake Uptake ≤ mediastinum Uptake >mediastinum but ≤ liver Uptake moderately increased compared to liver at any site Uptake markedly increased compared to the liver at any site or/and new sites of disease

Secondary Outcome Measures

1. Overall Response Rate [4-6 months]

   The number of patients that achieved a complete Metabolic Response (CR) or Partial Metabolic Response (PR) to therapy as assessed by the revised International Working Group Criteria. Complete Metabolic Response: Lymph nodes and extralymphatic sites: Score 1, 2, or 3 with or without a residual mass on 5-point (Daeuville) scale Bone Marrow: No evidence of FDG-avi disease No new lesions Partial Metabolic Response: >Lymph nodes and extralymphatic sites: Score 4, 5 with reduced uptake compared with baseline and residual mass(es) of any size. Deauville Criteria for PET scan Interpretation in Lymphoma Five-point scale: No Uptake Uptake ≤ mediastinum Uptake >mediastinum but ≤ liver Uptake moderately increased compared to liver at any site Uptake markedly increased compared to the liver at any site or/and new sites of disease

2. Number of Patients With Grade III and IV Adverse Events [4-6 months]

   The number of patients that experienced grade III and grade IV adverse events that were deemed to be possibly, probably, or definitely related to study treatment. Adverse events were assessed using Common Toxicology Criteria for Adverse Events (CTCAE v4.0) criteria.

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, or IIA classical Hodgkin Lymphoma

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

• Measurable disease ≥1.5 cm

• Age ≥18

• ECOG performance status 0-2 (see Appendix B)

• Participants must have initial organ and marrow function as defined below:

• Absolute neutrophil count ≥ 1,000/mcL

• Platelets ≥100,000/mcL

• Total bilirubin ≤ 2, unless due to Gilbert's disease

• AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional upper limit of normal

• Creatinine clearance ≥ 30 mL/min

• LVEF by echocardiogram or MUGA within institutional normal limits

• Participant must be willing to use two effective forms of birth control during protocol therapy. Men and women must continue using two effective forms of birth control for 6 months following treatment.

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Participants who have had prior cHL-directed chemotherapy or radiotherapy

• Participants may not be receiving any other investigational agents

• Participants with known CNS involvement of lymphoma

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Adriamycin, Dacarbazine, or brentuximab

• Pre-existing grade 2 or greater neuropathy

• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Pregnant women are excluded from this study because brentuximab is an antibody drug conjugate with a linked potent anti-tubule agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with brentuximab, breastfeeding should be discontinued if the mother is treated with brentuximab. These potential risks may also apply to other agents used in this study.

• Participants with a history of a different malignancy are ineligible unless they have been disease free for 1 year and considered at low risk for relapse, except for: cervical cancer in situ, ductal carcinoma in situ, localized prostate cancer with no detectable disease by imaging studies, and non-melanoma cancers of the skin, which are eligible at any time.

• Known HIV positivity

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Massachusetts General Hospital
• Seagen Inc.

Investigators

• Principal Investigator: Jeremy Abramson, MD, Massachusetts General Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 23, 2016

More Information

Publications

None provided.

• Responsible Party: Jeremy Abramson, MD, Principal Investigator, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT02505269
• Other Study ID Numbers: 15-196
• First Posted: Jul 22, 2015
• Last Update Posted: Aug 24, 2020
• Last Verified: Aug 1, 2020

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

Study Results

Participant Flow

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	The following procedures will take place during study visits beginning after the screening procedures: - Participants will receive combination therapy: Brentuximab Vedotin intravenously on predetermined days per cycle Adriamycin intravenously on predetermined days per cycle Dacarbazine intravenously on predetermined days per cycle Brentuximab Vedotin Adriamycin Dacarbazine
Period Title: Overall Study
STARTED	34
COMPLETED	34
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	The following procedures will take place during study visits beginning after the screening procedures: - Participants will receive combination therapy: Brentuximab Vedotin intravenously on predetermined days per cycle Adriamycin intravenously on predetermined days per cycle Dacarbazine intravenously on predetermined days per cycle Brentuximab Vedotin Adriamycin Dacarbazine
Overall Participants	34
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	36
Sex: Female, Male (Count of Participants)
Female	23 67.6%
Male	11 32.4%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (Count of Participants)
United States	34 100%

Outcome Measures

1. Primary Outcome

Title	Complete Response Rate
Description	The number of patients that achieved a complete response (CR) to therapy as assessed by the revised International Working Group Criteria. Complete response: Lymph nodes and extralymphatic sites: Score 1, 2, or 3 with or without a residual mass on 5-point (Daeuville) scale Bone Marrow: No evidence of FDG-avi disease No new lesions Deauville Criteria for PET scan Interpretation in Lymphoma Five-point scale: No Uptake Uptake ≤ mediastinum Uptake >mediastinum but ≤ liver Uptake moderately increased compared to liver at any site Uptake markedly increased compared to the liver at any site or/and new sites of disease
Time Frame	4-6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	The following procedures will take place during study visits beginning after the screening procedures: - Participants will receive combination therapy: Brentuximab Vedotin intravenously on predetermined days per cycle Adriamycin intravenously on predetermined days per cycle Dacarbazine intravenously on predetermined days per cycle Brentuximab Vedotin Adriamycin Dacarbazine
Measure Participants	34
Count of Participants [Participants]	34 100%

2. Secondary Outcome

Title	Overall Response Rate
Description	The number of patients that achieved a complete Metabolic Response (CR) or Partial Metabolic Response (PR) to therapy as assessed by the revised International Working Group Criteria. Complete Metabolic Response: Lymph nodes and extralymphatic sites: Score 1, 2, or 3 with or without a residual mass on 5-point (Daeuville) scale Bone Marrow: No evidence of FDG-avi disease No new lesions Partial Metabolic Response: >Lymph nodes and extralymphatic sites: Score 4, 5 with reduced uptake compared with baseline and residual mass(es) of any size. Deauville Criteria for PET scan Interpretation in Lymphoma Five-point scale: No Uptake Uptake ≤ mediastinum Uptake >mediastinum but ≤ liver Uptake moderately increased compared to liver at any site Uptake markedly increased compared to the liver at any site or/and new sites of disease
Time Frame	4-6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	The following procedures will take place during study visits beginning after the screening procedures: - Participants will receive combination therapy: Brentuximab Vedotin intravenously on predetermined days per cycle Adriamycin intravenously on predetermined days per cycle Dacarbazine intravenously on predetermined days per cycle Brentuximab Vedotin Adriamycin Dacarbazine
Measure Participants	34
Count of Participants [Participants]	34 100%

3. Secondary Outcome

Title	Number of Patients With Grade III and IV Adverse Events
Description	The number of patients that experienced grade III and grade IV adverse events that were deemed to be possibly, probably, or definitely related to study treatment. Adverse events were assessed using Common Toxicology Criteria for Adverse Events (CTCAE v4.0) criteria.
Time Frame	4-6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	The following procedures will take place during study visits beginning after the screening procedures: - Participants will receive combination therapy: Brentuximab Vedotin intravenously on predetermined days per cycle Adriamycin intravenously on predetermined days per cycle Dacarbazine intravenously on predetermined days per cycle Brentuximab Vedotin Adriamycin Dacarbazine
Measure Participants	34
Grade III Adverse Events	4 11.8%
Grade IV Adverse Events	0 0%

Adverse Events

Time Frame	From the start of treatment until 30 days after the end of treatment (up to approximately 5 months)
Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	The following procedures will take place during study visits beginning after the screening procedures: - Participants will receive combination therapy: Brentuximab Vedotin intravenously on predetermined days per cycle Adriamycin intravenously on predetermined days per cycle Dacarbazine intravenously on predetermined days per cycle Brentuximab Vedotin Adriamycin Dacarbazine
All Cause Mortality
	Brentuximab Vedotin
	Affected / at Risk (%)	# Events
Total	0/34 (0%)
Serious Adverse Events
	Brentuximab Vedotin
	Affected / at Risk (%)	# Events
Total	5/34 (14.7%)
Gastrointestinal disorders
Colitis	1/34 (2.9%)
Nausea	1/34 (2.9%)
Vomiting	1/34 (2.9%)
Diarrhea	1/34 (2.9%)
Infections and infestations
Upper respiratory infection	1/34 (2.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/34 (2.9%)
Vascular disorders
Thromboembolic event	1/34 (2.9%)
Other (Not Including Serious) Adverse Events
	Brentuximab Vedotin
	Affected / at Risk (%)	# Events
Total	34/34 (100%)
Blood and lymphatic system disorders
Anemia	5/34 (14.7%)	6
Ear and labyrinth disorders
Tinnitus	2/34 (5.9%)	2
Endocrine disorders
Endocrine disorders - Other, specify	3/34 (8.8%)	3
Eye disorders
Blurred vision	2/34 (5.9%)	2
Dry eye	2/34 (5.9%)	2
Gastrointestinal disorders
Abdominal pain	5/34 (14.7%)	6
Bloating	2/34 (5.9%)	4
Constipation	18/34 (52.9%)	24
Diarrhea	4/34 (11.8%)	4
Dry mouth	3/34 (8.8%)	3
Dyspepsia	6/34 (17.6%)	9
Gastroesophageal reflux disease	5/34 (14.7%)	6
Gastrointestinal disorders - Other, specify	5/34 (14.7%)	5
Gingival pain	2/34 (5.9%)	3
Mucositis oral	6/34 (17.6%)	8
Nausea	27/34 (79.4%)	39
Vomiting	5/34 (14.7%)	5
General disorders
Fatigue	21/34 (61.8%)	29
Fever	3/34 (8.8%)	3
General disorders and administration site conditions - Other, specify	2/34 (5.9%)	3
Neck edema	2/34 (5.9%)	4
Non-cardiac chest pain	4/34 (11.8%)	5
Infections and infestations
Upper respiratory infection	4/34 (11.8%)	4
Investigations
Alanine aminotransferase increased	7/34 (20.6%)	9
Aspartate aminotransferase increased	7/34 (20.6%)	9
Lymphocyte count decreased	2/34 (5.9%)	2
Neutrophil count decreased	8/34 (23.5%)	11
White blood cell decreased	6/34 (17.6%)	10
Metabolism and nutrition disorders
Anorexia	6/34 (17.6%)	7
Hyperglycemia	4/34 (11.8%)	7
Musculoskeletal and connective tissue disorders
Arthralgia	4/34 (11.8%)	7
Back pain	2/34 (5.9%)	3
Myalgia	4/34 (11.8%)	4
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	2/34 (5.9%)	2
Nervous system disorders
Concentration impairment	2/34 (5.9%)	2
Dysgeusia	4/34 (11.8%)	4
Headache	9/34 (26.5%)	13
Paresthesia	5/34 (14.7%)	6
Peripheral sensory neuropathy	21/34 (61.8%)	29
Psychiatric disorders
Anxiety	9/34 (26.5%)	10
Insomnia	2/34 (5.9%)	2
Reproductive system and breast disorders
Breast pain	2/34 (5.9%)	2
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	2/34 (5.9%)	2
Cough	7/34 (20.6%)	7
Dyspnea	4/34 (11.8%)	7
Hiccups	2/34 (5.9%)	2
Nasal congestion	7/34 (20.6%)	7
Sore throat	6/34 (17.6%)	7
Skin and subcutaneous tissue disorders
Alopecia	12/34 (35.3%)	14
Dry skin	3/34 (8.8%)	3
Erythema multiforme	2/34 (5.9%)	2
Pruritus	8/34 (23.5%)	8
Rash acneiform	2/34 (5.9%)	2
Rash maculo-papular	8/34 (23.5%)	16
Scalp pain	3/34 (8.8%)	3
Skin ulceration	2/34 (5.9%)	2
Vascular disorders
Flushing	3/34 (8.8%)	4
Hot flashes	4/34 (11.8%)	4

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.