Brentuximab Vedotin Combined With AVD Chemotherapy and 30 Gray Involved-Site Radiotherapy in Patients With Newly Diagnosed Early Stage, Unfavorable Risk Hodgkin Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborators:
Seattle Genetics, Inc.
University of Rochester
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01868451
First received: May 30, 2013
Last updated: August 20, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to find out whether BV with AVD chemotherapy and radiation is a safe and effective treatment. It is hoped that this treatment will improve the ability to cure more patients with HL.


Condition Intervention
Hodgkin Lymphoma
Drug: Brentuximab vedotin (SGN-35)
Drug: Doxorubicin HCL
Drug: Vinblastine Sulfate
Device: Dacarbazine
Radiation: Involved-Site Radiation Therapy (ISRT)
Procedure: Interim PET
Drug: Neupogen

Study Type: Interventional
Study Design: 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 and 30 Gray Involved-Site Radiotherapy 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).


Secondary Outcome Measures:
  • progression-free survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Progression free survival (PFS) will be calculated from the time of initiation of brentuximab vedotin.

  • 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.

  • Evaluate the prognostic significance of gene-expression based predictor [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    using NanoString technology

  • Evaluate the prognostic significance of gene-expression of plasma Epstein Barr virus DNA (EBV-DNA) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    by quantitative PCR,


Estimated Enrollment: 30
Study Start Date: May 2013
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pts with Hodgkin Lymphoma
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 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. Dosing of Neupogen can be determined at the discretion of the physician. Typically, Neupogen is administered for 3-5 days at the time of nadir (approximately 5-10 days after each treatment).
Drug: Brentuximab vedotin (SGN-35) Drug: Doxorubicin HCL Drug: Vinblastine Sulfate Device: Dacarbazine Radiation: Involved-Site Radiation Therapy (ISRT) Procedure: Interim PET Drug: Neupogen

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
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
  • At least one of the following unfavorable risk factors as defined by GHSG: bulky mediastinal mass (≥one-third maximum transverse thoracic diameter on Posterior-Anterior/Lateral Chest X-ray or ≥10cm by CT imaging in axial plane), ESR ≥ 50mm/h or ESR ≥30 mm/h in patients with "B" symptoms, extranodal involvement, or 3 or more involved lymph node sites. Patients with infradiaphragmatic disease which is considered an unfavorable risk feature are eligible regardless of whether they meet one of the aforementioned unfavorable risk factors as defined by the GHSG.
  • 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 < 60%
  • ANC≤1000/μl and Platelets≤75,000/μl
  • Total bilirubin ≥ 2.0 mg/dl in the absence of a history of Gilbert's disease
  • 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, 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 Cancer Center at Phelps Memorial Hospital Center Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: Craig Moskowitz, MD    212-639-2696      
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Seattle Genetics, Inc.
University of Rochester
Investigators
Principal Investigator: Craig Moskowitz, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

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: August 20, 2014
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:
Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Dacarbazine
Liposomal doxorubicin
Doxorubicin
Vinblastine
Antibodies, Monoclonal
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 21, 2014