Brentuximab Vedotin (SGN-35) in Transplant Eligible Patients With Relapsed or Refractory Hodgkin Lymphoma

This study is currently recruiting participants.
Verified October 2013 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborator:
Seattle Genetics, Inc.
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01508312
First received: January 9, 2012
Last updated: October 16, 2013
Last verified: October 2013
  Purpose

The purpose of this study is determine if 2 cycles of SGN-35 can be used instead of ICE prior to autologous stem cell transplant (ASCT) for relapsed and refractory HL. There are 2 steps to treating patients with relapsed or refractory HL. The first step is to shrink the lymphoma with chemotherapy. The chemotherapy regimen commonly used is called ICE. ICE is a combination of chemotherapy drugs: ifosfamide, carboplatin, and etoposide. The second step of treatment is to give high doses of chemotherapy and radiation therapy followed by infusion of stem cells. This is called an ASCT. This study will focus on the first step of treatment for relapsed and refractory HL.

ICE chemotherapy can cause many side effects. We believe that there are patients who can receive less toxic treatments and still do well. We have learned from past studies that [18F]FDG-PET scans (which we will call "PET scans") can be used to predict who will do well after ASCT. PET scans are tests used to measure the metabolic activity of the disease. Patients without abnormal activity on their PET scan (negative PET scan) before ASCT are much more likely to be cured than those with activity on their PET scan (positive PET scan).

In this study, instead of beginning with ICE chemotherapy, the patient will receive a new drug called Brentuximab vedotin (SGN-35). SGN-35 is a type of drug called an antibody drug conjugate. SGN-35 has 2 parts; a part that targets cancer cells (the antibody) and a cell killing part (the chemotherapy). The antibody part of SGN-35 sticks to a target called CD30. CD30 is an important molecule on some cancer cells (including Hodgkin lymphoma) and some normal cells of the immune system. The cell killing part of SGN-35 is a chemotherapy called monomethyl auristatin E (MMAE).

It can kill cells that the antibody part of SGN-35 sticks to.

Compared to ICE chemotherapy, SGN-has fewer side effects and does not require inpatient admission for treatment. We aim to determine whether patients can avoid treatment with ICE prior to ASCT. We will use the results of the PET scan to determine whether the patient needs additional chemotherapy before ASCT. If the PET scan is negative, the patient will be referred to ASCT and not receive ICE chemotherapy. If the PET scan is positive, the physician will discuss further treatment options with the patient.


Condition Intervention Phase
Hodgkin's Lymphoma
Drug: brentuximab vedotin (SGN-35)
Drug: Brentuximab Vedotin (SGN-35)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Brentuximab Vedotin (SGN-35) in Transplant Eligible Patients With Relapsed or Refractory Hodgkin Lymphoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • rate of FDG-PET/CT normalization [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Following salvage therapy with brentuximab vedotin (SGN-35) alone or followed by augmented ICE chemotherapy.


Secondary Outcome Measures:
  • overall response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    (CR and PR) rate to brentuximab vedotin alone

  • Toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 46
Study Start Date: January 2012
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FDG-PET abnormal
Patients will receive 2 cycles of weekly brentuximab vedotin and then undergo evaluation with FDGPET/CT. Patients with normalization of FDG-PET/CT will proceed to ASCT. Patients with persistent abnormalities on FDG-PET/CT will receive 2 cycles of augmented ICE chemotherapy followed by repeat FDG-PET/CT prior to ASCT. Following augmented ICE, patients with negative FDG-PET/CT will proceed to ASCT. Those with persistent abnormalities on FDG-PET/CT will be treated according to their physician's recommendations.
Drug: brentuximab vedotin (SGN-35)
Patients will receive 2 cycles of weekly brentuximab vedotin, 1.2mg/kg on days 1, 8, and 15 of each 28 day cycle. Patients with pre-treatment positive bone marrow biopsies will have repeat bone marrow biopsies if the PET scan is negative. FDG-PET/CT will be repeated after 2 cycles of treatment within 1 week of the last dose of cycle 2. Patients with persistent abnormalities on FDG-PET/CT following 2 cycles of brentuximab vedotin will receive 2 cycles of augmented ICE. The first cycle of augmented ICE will be initiated 7-14 days after the last dose of SGN-35. FDG-PET/CT will be repeated within 7-14 days following the second cycle of augmented ICE. Stem cell mobilization can be performed following the first or second cycle of augmented ICE.
Experimental: FDG-PET normalization
Patients will receive 2 cycles of weekly brentuximab vedotin and then undergo evaluation with FDGPET/CT. Patients with normalization of FDG-PET/CT will proceed to ASCT. Patients with persistent abnormalities on FDG-PET/CT will receive 2 cycles of augmented ICE chemotherapy followed by repeat FDG-PET/CT prior to ASCT. Following augmented ICE, patients with negative FDG-PET/CT will proceed to ASCT. Those with persistent abnormalities on FDG-PET/CT will be treated according to their physician's recommendations.
Drug: Brentuximab Vedotin (SGN-35)
Patients will receive 2 cycles of weekly brentuximab vedotin, 1.2mg/kg on days 1, 8, and 15 of each 28 day cycle. FDG-PET/CT will be repeated after 2 cycles of treatment within 1 week of the last dose of cycle 2. Patients with pre-treatment positive bone marrow biopsies will have repeat bone marrow biopsies if the PET scan is negative. Patients with normalization of FDG-PET/CT and negative bone marrow biopsies following 2 cycles of brentuximab vedotin will undergo stem cell mobilization in preparation for ASCT.

  Eligibility

Ages Eligible for Study:   12 Years to 72 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologic diagnosis of cd30 positive classical Hodgkin's lymphoma.
  • Primary refractory or relapsed disease proven by biopsy or fine needle aspiration (cytology) of an involved site. Pathology must be reviewed at MSKCC.
  • Relapse or refractory disease following doxorubicin or nitrogen mustard containing front-line therapy
  • Fluorodeoxyglucose (FDG)-avid disease by FDG-PET/CT and measurable disease of at least 1.5 cm by spiral CT, as assessed by the site radiologist.
  • Cardiac ejection fraction of greater than 45%, measured since last chemotherapy.
  • Hemoglobin-adjusted diffusing capacity for carbon monoxide of greater than 50% on pulmonary function testing, measured since last chemotherapy
  • Serum creatinine < or = to 1.5 mg/dl; if creatinine >1.5 mg/dl then the measured 12- or 24-hour creatinine clearance must be >60 ml/minute.
  • ANC>1000/μl and Platelets>50,000/μl
  • Total bilirubin < 2.0 mg/dl in the absence of a history of Gilbert's disease.
  • Females of childbearing age must be on an acceptable form of birth control.
  • Age between 12 and 72
  • HIV I and II negative.

Exclusion Criteria:

  • Received more than 1 prior treatment (combined modality therapy represents 1 treatment) for Hodgkin Lymphoma
  • Hepatitis B surface antigen positive or hepatitis B core antibody positive.
  • Known pregnancy or breast-feeding.
  • Medical illness unrelated to Hodgkin's Lymphoma, which, in the opinion of the attending physician and/or principal investigator, makes participation in this study inappropriate.
  • Peripheral neuropathy > grade 2
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01508312

Contacts
Contact: Allison Moskowitz, MD 212-639-4839
Contact: Craig Moskowitz, MD 212-639-2696

Locations
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Allison Moskowitz, MD    212-639-4839      
Contact: Craig Moskowitz, MD    212-639-2696      
Principal Investigator: Allison Moskowitz, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Seattle Genetics, Inc.
Investigators
Principal Investigator: Allison Moskowitz, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01508312     History of Changes
Other Study ID Numbers: 11-142
Study First Received: January 9, 2012
Last Updated: October 16, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
CARBOPLATIN
ETOPOSIDE (VP-16)
IFOSFAMIDE
SGN-35 (BRENTUXIMAB VEDOTIN)
11-142

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014