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

Primary Purpose

Hodgkin Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Brentuximab Vedotin
Adriamycin
Dacarbazine
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hodgkin Lymphoma focused on measuring limited stage, Hodgkin's disease, non-bulky

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Massachusetts General Hospital
  • Dana Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Brentuximab Vedotin

Arm 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

Outcomes

Primary Outcome Measures

Complete Response Rate
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

Overall Response Rate
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
Number of Patients With Grade III and IV Adverse Events
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.

Full Information

First Posted
July 20, 2015
Last Updated
August 10, 2020
Sponsor
Massachusetts General Hospital
Collaborators
Seagen Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02505269
Brief Title
Brentuximab Vedotin Plus AD in Non-bulky Limited Stage Hodgkin Lymphoma
Official Title
Brentuximab Vedotin Plus AD in Non-bulky Limited Stage Hodgkin Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
August 7, 2015 (Actual)
Primary Completion Date
June 2019 (Actual)
Study Completion Date
June 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Seagen Inc.

4. Oversight

Data Monitoring Committee
Yes

5. 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hodgkin Lymphoma
Keywords
limited stage, Hodgkin's disease, non-bulky

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
34 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Brentuximab Vedotin
Arm Type
Experimental
Arm 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
Intervention Type
Drug
Intervention Name(s)
Brentuximab Vedotin
Other Intervention Name(s)
Adcetris
Intervention Type
Drug
Intervention Name(s)
Adriamycin
Other Intervention Name(s)
Doxorubicin, Rubex ®
Intervention Type
Drug
Intervention Name(s)
Dacarbazine
Other Intervention Name(s)
DTIC-Dome®, DTIC, DIC, Imidazole Carboxamide
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeremy Abramson, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
36053786
Citation
Abramson JS, Bengston E, Redd R, Barnes JA, Takvorian T, Sokol L, Lansigan F, Armand P, Shah B, Jacobsen E, Martignetti R, Turba E, Metzler S, Patterson V, LaCasce AS, Bello CM. Brentuximab vedotin plus doxorubicin and dacarbazine in nonbulky limited-stage classical Hodgkin lymphoma. Blood Adv. 2023 Apr 11;7(7):1130-1136. doi: 10.1182/bloodadvances.2022008420.
Results Reference
derived

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

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