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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2016 by Memorial Sloan Kettering Cancer Center
Sponsor:
Collaborators:
Seattle Genetics, Inc.
University of Rochester
City of Hope Medical Center
Stanford University
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01868451
First received: May 30, 2013
Last updated: October 11, 2016
Last verified: October 2016
  Purpose
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.

Condition Intervention
Hodgkin Lymphoma
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 Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Brentuximab Vedotin Combined With AVD Chemotherapy in Patients With Newly Diagnosed Early Stage, Unfavorable Risk Hodgkin Lymphoma

Resource links provided by NLM:


Further study details as provided by Memorial Sloan Kettering Cancer Center:

Primary Outcome Measures:
  • development of significant pulmonary toxicity [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    (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.


Estimated Enrollment: 117
Study Start Date: May 2013
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 (Neupogen) starting with cycle 1.
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.
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
Eligible 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.
Drug: Brentuximab vedotin (SGN-35) Drug: Doxorubicin HCL Drug: Vinblastine Sulfate Drug: Dacarbazine Procedure: Interim PET Radiation: consolidation volume RT (CVRT)
Experimental: Cohort 4
Eligible 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. 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.
Drug: Brentuximab vedotin (SGN-35) Drug: Doxorubicin HCL Drug: Vinblastine Sulfate Drug: Dacarbazine Procedure: Interim PET

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • Age between 18 and 60

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
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01868451

Contacts
Contact: Craig Moskowitz, MD 212-639-2696
Contact: Joachim Yahalom, MD 212-639-5999

Locations
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Elizabeth Budde, MD    626-256-4673      
Stanford University Medical Center Recruiting
Stanford, California, United States, 94305-5408
Contact: Ranjana Advani, MD    650-498-6000      
United States, New Jersey
Memorial Sloan Kettering at Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Craig Moskowitz, MD    212-639-2696      
United States, New York
Memorial Sloan Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Craig Moskowitz, MD    212-639-2696      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Craig Moskowitz, MD    212-639-2696      
Contact: Joachim Yahalom, MD    212-639-5999      
Principal Investigator: Craig Moskowitz, MD         
University of Rochester Medical Center Recruiting
Rochester, New York, United States
Contact: Carla Casulo, MD         
Principal Investigator: Carla Casulo, MD         
Memorial Sloan Kettering at Mercy Medical Center Recruiting
Rockville Centre, New York, United States
Contact: Craig Moskowitz, MD    212-639-2696      
Memorial Sloan Kettering Westchester Recruiting
West Harrison, New York, United States, 10604
Contact: Craig Moskowitz, MD    212-639-2696      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Seattle Genetics, Inc.
University of Rochester
City of Hope Medical Center
Stanford University
Investigators
Principal Investigator: Craig Moskowitz, MD Memorial Sloan Kettering Cancer Center
  More Information

Additional Information:
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01868451     History of Changes
Other Study ID Numbers: 13-034 
Study First Received: May 30, 2013
Last Updated: October 11, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan Kettering Cancer Center:
DACARBAZINE
DOXORUBICIN/ADRIAMYCIN
SGN-35 (BRENTUXIMAB VEDOTIN)
VINBLASTINE
Involved-site radiation therapy (ISRT)
Early stage
13-034

Additional relevant MeSH terms:
Lymphoma
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Doxorubicin
Liposomal doxorubicin
Vinblastine
Antibodies, Monoclonal
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on December 02, 2016