Brentuximab Vedotin for Steroid Refractory GvHD

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Massachusetts General Hospital
Sponsor:
Collaborators:
Seattle Genetics, Inc.
Dana-Farber Cancer Institute
Information provided by (Responsible Party):
Yi-Bin A. Chen, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01596218
First received: May 9, 2012
Last updated: April 21, 2014
Last verified: April 2014
  Purpose

This research study is a Phase I clinical trial. Phase I clinical trials test the safety of an investigational drug. Phase I studies also try to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it. It also means that the FDA has not approved brentuximab vedotin for the treatment of GVHD.

Currently, corticosteroids are the standard/first line of treatment for people with GVHD. However, some patients do not achieve a good response with steroids and other experience flare-ups while tapering steroid treatment. Corticosteroid treatment has also led to a weakening of the immune system. For this reason, there have been increased attempts by researchers to find other options for the treatment of Graft vs. Host Disease.

Brentuximab vedotin is a drug that is FDA approved for the treatment of certain types of cancers, like Hodgkin's lymphoma. Recent research studies have found increased levels of protein called CD30 in people with acute GVHD. Brentuximab vedotin is designed to target CD30. Researchers have never tried to target the CD30 molecule for the treatment of GVHD, but results from other research studies show that it could help slow the growth of your disease.

In this research study, we are trying to determine the safest dose of brentuximab vedotin that can be given to patients with GVHD.


Condition Intervention Phase
Graft vs. Host Disease
Drug: Brentuximab Vedotin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of Brentuximab Vedotin for Steroid Refractory Acute Graft vs. Host Disease (GvHD)

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Define MTD of Brentuximab Vedotin [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To define the maximum tolerated dose (MTD) of brentuximab vedotin when given as treatment for steroid-refractory acute GVHD


Secondary Outcome Measures:
  • Overall Response Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To test the overall response rate of brentuximab vedotin when given as treatment for steroid refractory acute GVHD

  • Identification of Toxicities [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To identify the toxicities associated with brentuximab vedotin when used as therapy for steroid-refractory acute GVHD

  • Overall Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Overall survival at 100 days, 180 days and one year after first infusion

  • Description of Cumulative Incidence of Chronic GVHD [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To describe the cumulative incidence of chronic GVHD developing in patients with acute GVHD treated with brentuximab vedotin

  • Assessment of Levels of Soluble CD30 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To assess levels of soluble CD30 and surface CD30 expression on peripheral blood T-cells in patients with acute GVHD before and after the administration of brentuximab vedotin

  • Assessment of Steroid Dose [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To assess dose of steroids (mg/kg/day of prednisone equivalent) at 6 and 12 months after starting therapy


Estimated Enrollment: 28
Study Start Date: July 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm
Treatment Arm for all participants
Drug: Brentuximab Vedotin
Starting dose is 0.6 mg/kg weekly x 3
Other Name: SGN-35

Detailed Description:

This study will be broken up into two parts: induction and maintenance. The induction phase will last for 28 days and the maintenance phase will last for 12 weeks.

Since we are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects in participants that have Graft vs. Host Disease, not everyone who participates in this research study will receive the same dose of the study drug. The dose you get will depend on the number of participants who have been enrolled in the study before you and how well they have tolerated their doses.

The induction phase of the trial involves finding the safest dose of brentuximab vedotin. In this phase, participants will receive 3 weekly doses on days 1, 8 and 15 of the cycle. Brentuximab vedotin is administered via intravenous infusion, which means directly into the vein, over a period of about 30 minutes.

Additionally you will undergo the following tests and procedures when you come into the clinic to receive your brentuximab vedotin: physical exam, medical history, performance status, routine and research blood tests, assessment for side effects and acute/chronic GVHD.

If you are still on this study at the end of the induction phase, meaning you have had no serious side effects and your GVHD has not progressed, ou wil continue to the next phase of this study.

Participants in the maintenance phase will receive a total of 4 doses of brentuximab vedotin every 3 weeks for a total of 12 weeks. Day 1 of the maintenance phase will be the day after the 28 day induction phase ends. You will receive a dose of brentuximab vedotin via IV infusion on Day 1 of Weeks 1,4, 7 and 10. During these visits you will undergo the same tests, procedures and assessments as the induction phase.

You will have three follow up visits after your last dose of brentuximab vedotin at 6 months, 9 months and 12 months after the end of the maintenance phase. You also have the option to talk to your physician about continuing treatment with brentuximab vedotin. However, brentuximab vedotin will only be provided by the study for the 12 week maintenance period. Afterward, brentuximab vedotin will need to be covered by your insurance or paid for out of pocket.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Acute GVHD
  • Corticosteroid refractory

Exclusion Criteria:

  • Pregnant or breastfeeding
  • Requiring mechanical ventilation
  • Concurrent hepatic VOD
  • Have received another study agent within 7 days
  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: NCT01596218

Contacts
Contact: Yi-Bin Chen, MD 6177241124 ychen6@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Yi-Bin Chen, MD    617-724-1124    ychen6@partners.org   
Contact: Candice Del Rio, RN    617-726-6034    cdelrio@partners.org   
Principal Investigator: Yi-Bin Chen, MD         
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Corey Cutler, MD    617-632-5946    cscutler@partners.org   
Principal Investigator: Corey Cutler, MD         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Corey Cutler, MD    617-632-5946    cscutler@partners.org   
Principal Investigator: Corey Cutler, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States
Contact: Miguel Perales, MD    212-639-8682      
Principal Investigator: Miguel Perales, MD         
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States
Contact: Yvonne Efebera    614-293-2268      
Principal Investigator: Yvonne Efebera, MD         
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States
Contact: Madan Jagasia, MD    615-322-1770      
Principal Investigator: Madan Jagasia, MD         
Sponsors and Collaborators
Massachusetts General Hospital
Seattle Genetics, Inc.
Dana-Farber Cancer Institute
Investigators
Principal Investigator: Yi-Bin Chen, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Yi-Bin A. Chen, MD, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01596218     History of Changes
Other Study ID Numbers: 12-094
Study First Received: May 9, 2012
Last Updated: April 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
Steroid Refractory
Acute

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014