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

Primary Purpose

Hodgkin Lymphoma, Adult

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Brentuximab vedotin
ABVD
Sponsored by
UNC Lineberger Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hodgkin Lymphoma, Adult focused on measuring Hodgkin's lymphoma, Hodgkin lymphoma

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • City of Hope Comprehensive Cancer Center
  • Mayo Clinic
  • University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center
  • Levine Cancer Istitute, Carolinas Health Care system
  • Rex Cancer Center
  • Vanderbilt University

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

ABVD followed by Brentuximab vedotin

Arm Description

Single arm trial

Outcomes

Primary Outcome Measures

Percentage of Patients With Positron Emission Tomography (PET) Negative Disease
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

Number of Participant Who Achieved a Complete Response
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.
Conversion Rate to Complete Response. Number of Participants Who Had a Partial Response Post ABVD Who Converted to a Complete Response.
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 Year Progression Free Survival Rate
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
3 Year Time to Progression Rate
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
Number of Adverse Events Attributed to Brentuximab Vedotin With a Grade 3 or Higher
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.

Full Information

First Posted
April 13, 2012
Last Updated
November 8, 2021
Sponsor
UNC Lineberger Comprehensive Cancer Center
Collaborators
Seagen Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01578967
Brief Title
Induction Chemo w/ABVD Followed by Brentuximab Vedotin Consolidation in Newly Diagnosed, Non-Bulky Stage I/II Hodgkin Lymphoma
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 Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
April 2012 (undefined)
Primary Completion Date
August 10, 2016 (Actual)
Study Completion Date
December 11, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UNC Lineberger Comprehensive Cancer Center
Collaborators
Seagen Inc.

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hodgkin Lymphoma, Adult
Keywords
Hodgkin's lymphoma, Hodgkin lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ABVD followed by Brentuximab vedotin
Arm Type
Other
Arm Description
Single arm trial
Intervention Type
Drug
Intervention Name(s)
Brentuximab vedotin
Other Intervention Name(s)
SGN-35, Adcetris
Intervention Description
IV, 1.8mg/kg, every 3 weeks for 6 cycles.
Intervention Type
Drug
Intervention Name(s)
ABVD
Intervention Description
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.
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
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
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
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
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Shea, MD
Organizational Affiliation
UNC Lineberger Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Comprehensive Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Levine Cancer Istitute, Carolinas Health Care system
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Rex Cancer Center
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27607
Country
United States
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37240
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
32516414
Citation
Park SI, Shea TC, Olajide O, Reddy NM, Budde LE, Ghosh N, Deal AM, Noe JF, Ansell SM. ABVD followed by BV consolidation in risk-stratified patients with limited-stage Hodgkin lymphoma. Blood Adv. 2020 Jun 9;4(11):2548-2555. doi: 10.1182/bloodadvances.2020001871.
Results Reference
derived
Links:
URL
http://unclineberger.org/
Description
UNC Lineberger Comprehensive Cancer Center

Learn more about this trial

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

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