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

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ClinicalTrials.gov Identifier: NCT01868451
Recruitment Status : Active, not recruiting
First Posted : June 4, 2013
Last Update Posted : July 29, 2020
Sponsor:
Collaborators:
Seagen Inc.
University of Rochester
City of Hope Medical Center
Stanford University
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE May 30, 2013
First Posted Date  ICMJE June 4, 2013
Last Update Posted Date July 29, 2020
Actual Study Start Date  ICMJE May 2013
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 11, 2016)
  • development of significant pulmonary toxicity [ Time Frame: 1 year ]
    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) [ Time Frame: 1 year ]
    Evaluate the rate of PET-negative complete responses after completion of the treatment program (8 weeks (+/- 2 weeks) after completion of radiotherapy).
Original Primary Outcome Measures  ICMJE
 (submitted: May 30, 2013)
development of significant pulmonary toxicity [ Time Frame: 1 year ]
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).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 11, 2016)
Evaluate the prognostic significance [ Time Frame: 1 year ]
(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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 30, 2013)
  • progression-free survival [ Time Frame: 1 year ]
    Progression free survival (PFS) will be calculated from the time of initiation of brentuximab vedotin.
  • Evaluate the prognostic significance [ Time Frame: 1 year ]
    (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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Brentuximab Vedotin Combined With AVD Chemotherapy in Patients With Newly Diagnosed Early Stage, Unfavorable Risk Hodgkin Lymphoma
Official Title  ICMJE A Pilot Study of Brentuximab Vedotin Combined With AVD Chemotherapy in Patients With Newly Diagnosed Early Stage, Unfavorable Risk Hodgkin Lymphoma
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hodgkin Lymphoma
Intervention  ICMJE
  • Drug: Brentuximab vedotin (SGN-35)
  • Drug: Doxorubicin HCL
  • Drug: Vinblastine Sulfate
  • Drug: Dacarbazine
  • Radiation: Involved-Site Radiation Therapy (ISRT)
  • Procedure: Interim PET
  • Radiation: consolidation volume RT (CVRT)
Study Arms  ICMJE
  • Experimental: Cohort 1 (completed accrual)
    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.
    Interventions:
    • Drug: Brentuximab vedotin (SGN-35)
    • Drug: Doxorubicin HCL
    • Drug: Vinblastine Sulfate
    • Drug: Dacarbazine
    • Radiation: Involved-Site Radiation Therapy (ISRT)
    • Procedure: Interim PET
  • Experimental: Cohort 2
    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.
    Interventions:
    • Drug: Brentuximab vedotin (SGN-35)
    • Drug: Doxorubicin HCL
    • Drug: Vinblastine Sulfate
    • Drug: Dacarbazine
    • Radiation: Involved-Site Radiation Therapy (ISRT)
    • Procedure: Interim PET
  • Experimental: Cohort 3
    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.
    Interventions:
    • Drug: Brentuximab vedotin (SGN-35)
    • Drug: Doxorubicin HCL
    • Drug: Vinblastine Sulfate
    • Drug: Dacarbazine
    • Procedure: Interim PET
    • Radiation: consolidation volume RT (CVRT)
  • Experimental: Cohort 4
    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.
    Interventions:
    • Drug: Brentuximab vedotin (SGN-35)
    • Drug: Doxorubicin HCL
    • Drug: Vinblastine Sulfate
    • Drug: Dacarbazine
    • Procedure: Interim PET
Publications * Kumar A, Casulo C, Yahalom J, Schöder 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 20, 2019)
118
Original Estimated Enrollment  ICMJE
 (submitted: May 30, 2013)
30
Estimated Study Completion Date  ICMJE May 2021
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01868451
Other Study ID Numbers  ICMJE 13-034
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE
  • Seagen Inc.
  • University of Rochester
  • City of Hope Medical Center
  • Stanford University
Investigators  ICMJE
Principal Investigator: Anita Kumar, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP