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Brentuximab Vedotin Combined With AVD Chemotherapy in Patients With Newly Diagnosed Early Stage, Unfavorable Risk Hodgkin Lymphoma

Primary Purpose

Hodgkin Lymphoma

Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Brentuximab vedotin (SGN-35)
Doxorubicin HCL
Vinblastine Sulfate
Dacarbazine
Involved-Site Radiation Therapy (ISRT)
Interim PET
consolidation volume RT (CVRT)
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hodgkin Lymphoma focused on measuring DACARBAZINE, DOXORUBICIN/ADRIAMYCIN, SGN-35 (BRENTUXIMAB VEDOTIN), VINBLASTINE, Involved-site radiation therapy (ISRT), Early stage, 13-034

Eligibility Criteria

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

Inclusion Criteria:

  • Histologic diagnosis of classical, CD30 positive Hodgkin lymphoma confirmed at enrolling institution
  • FDG-avid disease by FDG-PET/CT and measurable disease of at least 1.5 cm by CT
  • Ann Arbor Stage I or II disease
  • Disease bulk defined as any lymph node mass with transverse maximal diameter > 7.0 cm OR coronal maximal diameter > 7.0 cm on CT imaging
  • Females of childbearing age must be on an acceptable form of birth control per institutional standards
  • Ages 18 and over

Exclusion Criteria:

  • Cardiac ejection fraction ≤ 50%
  • Hemoglobin-adjusted diffusing capacity for carbon monoxide < 40%
  • ANC≤1000/μl and Platelets≤75,000/μl
  • Total bilirubin ≥ 2.0 mg/dl in the absence of a history of Gilbert's disease
  • Serum creatinine clearance of <30 mL/min as estimated by the Cockcroft-Gault Method
  • Known pregnancy or breast-feeding
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • Medical illness unrelated to Hodgkin Lymphoma, which, in the opinion of the attending physician and/or MSKCC principal investigator, makes participation in this study inappropriate.
  • Peripheral neuropathy > grade 1
  • Patients receiving chronic treatment with systemic steroids. However, patients can receive up to 10 days of steroid therapy prior to starting treatment with BV+AVD.

Sites / Locations

  • City of Hope
  • Stanford University Medical Center
  • Memorial Sloan Kettering Basking Ridge
  • Memorial Sloan Kettering Monmouth
  • Memorial Sloan Kettering Bergen
  • Memorial Sloan Kettering Commack
  • Memorial Sloan Kettering Westchester
  • Memorial Sloan Kettering Cancer Center
  • University of Rochester Medical Center
  • Memorial Sloan Kettering Nassau

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1 (completed accrual)

Cohort 2

Cohort 3

Cohort 4

Arm Description

Patients received 4 cycles of brentuximab vedotin & AVD chemotherapy. Brentuximab vedotin, 1.2 mg/kg, will be administered on days 1 and 15 of each 28 day cycle. Doxorubicin 25 mg/m2, Vinblastine 6 mg/m2, & Dacarbazine 375 mg/m2 will be administered on days 1 and 15 of each 28 day cycle. This may be followed by 30 Gy involved site radiotherapy. Involved site radiotherapy should be initiated from 12 days to 42 days after completion of chemotherapy. It is mandatory to administer prophylactic growth factor support starting with cycle 1. Choice of growth factor and dosing can be determined at the discretion of the treating physican.

Patients with early stage, unfavorable risk Hodgkin lymphoma. The definition of disease bulk, one of the unfavorable risk features, has been updated, and is defined as the presence of any lymph node mass with transverse maximal diameter > 7.0 cm OR coronal maximal diameter > 7.0 cm. Patients will receive 4 cycles of brentuximab vedotin & AVD chemotherapy. Brentuximab vedotin, 1.2 mg/kg, will be administered on days 1 and 15 of each 28 day cycle. Doxorubicin 25 mg/m2, Vinblastine 6 mg/m2, and Dacarbazine 375 mg/m2 will be administered on days 1 & 15 of each 28 day cycle. This may be followed by 20 Gy involved site radiotherapy.

Patients will have early stage, unfavorable risk classical Hodgkin lymphoma with disease bulk defined as the presence of any lymph node mass with transverse maximal diameter > 7.0 cm or coronal maximal diameter > 7.0 cm. Patients will receive 4 cycles of brentuximab vedotin and AVD chemotherapy. Brentuximab vedotin, 1.2 mg/kg, will be administered on days 1 and 15 of each 28 day cycle. Doxorubicin 25 mg/m2, Vinblastine 6 mg/m2, and Dacarbazine 375 mg/m2 will be administered on days 1 and 15 of each 28 day cycle. This may be followed by 30.6 Gy CVRT.

Patients will have early stage, unfavorable risk classical Hodgkin lymphoma with disease bulk defined as the presence of any lymph node mass with transverse maximal diameter > 7.0 cm or coronal maximal diameter > 7.0 cm. In this cohort. Pts will receive 4 cycles of brentuximab vedotin & AVD chemo. Brentuximab vedotin, 1.2 mg/kg, will be administered on days 1 & 15 of each 28 day cycle. Doxorubicin 25 mg/m2, Vinblastine 6 mg/m2, & Dacarbazine 375 mg/m2 will be administered on days 1 & 15 of each 28 day cycle. Pts whose PET scan is negative after 4 cycles of brentuximab vedotin & AVD chemotherapy will not receive RT. Pts whose PET scan is positive after 4 cycles of brentuximab vedotin & AVD chemo, but subsequent biopsy is neg, will also receive no RT. Upon MSK PI approval, if the simulation can't be covered by the institution or the pts insurance, a diagnostic IV contrast CT neck & diagnostic IV contrast CT CAP scan will be done in addition to the FDG-PET done after 4 cycles of chemo.

Outcomes

Primary Outcome Measures

development of significant pulmonary toxicity
specifically non-infectious pneumonitis The definition of unacceptable pulmonary toxicity will be defined as the development of grade 2 or higher pneumonitis as defined by Common Terminology Criteria for Adverse Events (CTCAE version 4).
complete responses (all cohorts)
Evaluate the rate of PET-negative complete responses after completion of the treatment program (8 weeks (+/- 2 weeks) after completion of radiotherapy).

Secondary Outcome Measures

Evaluate the prognostic significance
(i.e. correlation with progression free survival) of interim fluorodeoxyglucose-positron emission tomography (PET) in this patient population measured by visual analysis and semi-quantitative analysis.

Full Information

First Posted
May 30, 2013
Last Updated
July 6, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Seagen Inc., University of Rochester, City of Hope Medical Center, Stanford University
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1. Study Identification

Unique Protocol Identification Number
NCT01868451
Brief Title
Brentuximab Vedotin Combined With AVD Chemotherapy in Patients With Newly Diagnosed Early Stage, Unfavorable Risk Hodgkin Lymphoma
Official Title
A Pilot Study of Brentuximab Vedotin Combined With AVD Chemotherapy in Patients With Newly Diagnosed Early Stage, Unfavorable Risk Hodgkin Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 2013 (Actual)
Primary Completion Date
May 2026 (Anticipated)
Study Completion Date
May 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Seagen Inc., University of Rochester, City of Hope Medical Center, Stanford University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to compare the outcomes across the 4 different treatment groups. The investigators hope that this treatment will improve the ability to cure more patients with HL and also limit the long-term side effects from the treatment. Although eliminating radiation in cohort 4 will eliminate the risk for long-term side effects from radiation, it is also possible that with BV+AVD chemotherapy alone there may be an increased risk of the Hodgkin lymphoma coming back after initial treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hodgkin Lymphoma
Keywords
DACARBAZINE, DOXORUBICIN/ADRIAMYCIN, SGN-35 (BRENTUXIMAB VEDOTIN), VINBLASTINE, Involved-site radiation therapy (ISRT), Early stage, 13-034

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
118 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1 (completed accrual)
Arm Type
Experimental
Arm Description
Patients received 4 cycles of brentuximab vedotin & AVD chemotherapy. Brentuximab vedotin, 1.2 mg/kg, will be administered on days 1 and 15 of each 28 day cycle. Doxorubicin 25 mg/m2, Vinblastine 6 mg/m2, & Dacarbazine 375 mg/m2 will be administered on days 1 and 15 of each 28 day cycle. This may be followed by 30 Gy involved site radiotherapy. Involved site radiotherapy should be initiated from 12 days to 42 days after completion of chemotherapy. It is mandatory to administer prophylactic growth factor support starting with cycle 1. Choice of growth factor and dosing can be determined at the discretion of the treating physican.
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Patients with early stage, unfavorable risk Hodgkin lymphoma. The definition of disease bulk, one of the unfavorable risk features, has been updated, and is defined as the presence of any lymph node mass with transverse maximal diameter > 7.0 cm OR coronal maximal diameter > 7.0 cm. Patients will receive 4 cycles of brentuximab vedotin & AVD chemotherapy. Brentuximab vedotin, 1.2 mg/kg, will be administered on days 1 and 15 of each 28 day cycle. Doxorubicin 25 mg/m2, Vinblastine 6 mg/m2, and Dacarbazine 375 mg/m2 will be administered on days 1 & 15 of each 28 day cycle. This may be followed by 20 Gy involved site radiotherapy.
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
Patients will have early stage, unfavorable risk classical Hodgkin lymphoma with disease bulk defined as the presence of any lymph node mass with transverse maximal diameter > 7.0 cm or coronal maximal diameter > 7.0 cm. Patients will receive 4 cycles of brentuximab vedotin and AVD chemotherapy. Brentuximab vedotin, 1.2 mg/kg, will be administered on days 1 and 15 of each 28 day cycle. Doxorubicin 25 mg/m2, Vinblastine 6 mg/m2, and Dacarbazine 375 mg/m2 will be administered on days 1 and 15 of each 28 day cycle. This may be followed by 30.6 Gy CVRT.
Arm Title
Cohort 4
Arm Type
Experimental
Arm Description
Patients will have early stage, unfavorable risk classical Hodgkin lymphoma with disease bulk defined as the presence of any lymph node mass with transverse maximal diameter > 7.0 cm or coronal maximal diameter > 7.0 cm. In this cohort. Pts will receive 4 cycles of brentuximab vedotin & AVD chemo. Brentuximab vedotin, 1.2 mg/kg, will be administered on days 1 & 15 of each 28 day cycle. Doxorubicin 25 mg/m2, Vinblastine 6 mg/m2, & Dacarbazine 375 mg/m2 will be administered on days 1 & 15 of each 28 day cycle. Pts whose PET scan is negative after 4 cycles of brentuximab vedotin & AVD chemotherapy will not receive RT. Pts whose PET scan is positive after 4 cycles of brentuximab vedotin & AVD chemo, but subsequent biopsy is neg, will also receive no RT. Upon MSK PI approval, if the simulation can't be covered by the institution or the pts insurance, a diagnostic IV contrast CT neck & diagnostic IV contrast CT CAP scan will be done in addition to the FDG-PET done after 4 cycles of chemo.
Intervention Type
Drug
Intervention Name(s)
Brentuximab vedotin (SGN-35)
Intervention Type
Drug
Intervention Name(s)
Doxorubicin HCL
Intervention Type
Drug
Intervention Name(s)
Vinblastine Sulfate
Intervention Type
Drug
Intervention Name(s)
Dacarbazine
Intervention Type
Radiation
Intervention Name(s)
Involved-Site Radiation Therapy (ISRT)
Intervention Type
Procedure
Intervention Name(s)
Interim PET
Intervention Type
Radiation
Intervention Name(s)
consolidation volume RT (CVRT)
Primary Outcome Measure Information:
Title
development of significant pulmonary toxicity
Description
specifically non-infectious pneumonitis The definition of unacceptable pulmonary toxicity will be defined as the development of grade 2 or higher pneumonitis as defined by Common Terminology Criteria for Adverse Events (CTCAE version 4).
Time Frame
1 year
Title
complete responses (all cohorts)
Description
Evaluate the rate of PET-negative complete responses after completion of the treatment program (8 weeks (+/- 2 weeks) after completion of radiotherapy).
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Evaluate the prognostic significance
Description
(i.e. correlation with progression free survival) of interim fluorodeoxyglucose-positron emission tomography (PET) in this patient population measured by visual analysis and semi-quantitative analysis.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologic diagnosis of classical, CD30 positive Hodgkin lymphoma confirmed at enrolling institution FDG-avid disease by FDG-PET/CT and measurable disease of at least 1.5 cm by CT Ann Arbor Stage I or II disease Disease bulk defined as any lymph node mass with transverse maximal diameter > 7.0 cm OR coronal maximal diameter > 7.0 cm on CT imaging Females of childbearing age must be on an acceptable form of birth control per institutional standards Ages 18 and over Exclusion Criteria: Cardiac ejection fraction ≤ 50% Hemoglobin-adjusted diffusing capacity for carbon monoxide < 40% ANC≤1000/μl and Platelets≤75,000/μl Total bilirubin ≥ 2.0 mg/dl in the absence of a history of Gilbert's disease Serum creatinine clearance of <30 mL/min as estimated by the Cockcroft-Gault Method Known pregnancy or breast-feeding Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) Medical illness unrelated to Hodgkin Lymphoma, which, in the opinion of the attending physician and/or MSKCC principal investigator, makes participation in this study inappropriate. Peripheral neuropathy > grade 1 Patients receiving chronic treatment with systemic steroids. However, patients can receive up to 10 days of steroid therapy prior to starting treatment with BV+AVD.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anita Kumar, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Stanford University Medical Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305-5408
Country
United States
Facility Name
Memorial Sloan Kettering Basking Ridge
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Facility Name
Memorial Sloan Kettering Monmouth
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Facility Name
Memorial Sloan Kettering Bergen
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Facility Name
Memorial Sloan Kettering Commack
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Facility Name
Memorial Sloan Kettering Westchester
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
Country
United States
Facility Name
Memorial Sloan Kettering Nassau
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
33909449
Citation
Kumar A, Casulo C, Advani RH, Budde E, Barr PM, Batlevi CL, Caron P, Constine LS, Dandapani SV, Drill E, Drullinsky P, Friedberg JW, Grieve C, Hamilton A, Hamlin PA, Hoppe RT, Horwitz SM, Joseph A, Khan N, Laraque L, Matasar MJ, Moskowitz AJ, Noy A, Palomba ML, Schoder H, Straus DJ, Vemuri S, Yang J, Younes A, Zelenetz AD, Yahalom J, Moskowitz CH. Brentuximab Vedotin Combined With Chemotherapy in Patients With Newly Diagnosed Early-Stage, Unfavorable-Risk Hodgkin Lymphoma. J Clin Oncol. 2021 Jul 10;39(20):2257-2265. doi: 10.1200/JCO.21.00108. Epub 2021 Apr 28.
Results Reference
derived
PubMed Identifier
27458003
Citation
Kumar A, Casulo C, Yahalom J, Schoder H, Barr PM, Caron P, Chiu A, Constine LS, Drullinsky P, Friedberg JW, Gerecitano JF, Hamilton A, Hamlin PA, Horwitz SM, Jacob AG, Matasar MJ, McArthur GN, McCall SJ, Moskowitz AJ, Noy A, Palomba ML, Portlock CS, Straus DJ, VanderEls N, Verwys SL, Yang J, Younes A, Zelenetz AD, Zhang Z, Moskowitz CH. Brentuximab vedotin and AVD followed by involved-site radiotherapy in early stage, unfavorable risk Hodgkin lymphoma. Blood. 2016 Sep 15;128(11):1458-64. doi: 10.1182/blood-2016-03-703470. Epub 2016 Jul 25.
Results Reference
derived
Links:
URL
http://www.mskcc.org/
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

Brentuximab Vedotin Combined With AVD Chemotherapy in Patients With Newly Diagnosed Early Stage, Unfavorable Risk Hodgkin Lymphoma

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