Pilot Study of Brentuximab Vedotin (SGN-35) in Patients With MF With Variable CD30 Expression Level

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Stanford University
Sponsor:
Collaborator:
Seattle Genetics, Inc.
Information provided by (Responsible Party):
Youn Kim, Stanford University
ClinicalTrials.gov Identifier:
NCT01396070
First received: July 14, 2011
Last updated: July 9, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to learn the effects of an investigational medication, SGN 35, on patients with mycosis fungoides. Despite a wide range of therapeutic options, the treatments are associated with short response duration, thus this condition is largely incurable. This investigational drug may offer less toxicity than standard treatments and have better tumor specific targeting.


Condition Intervention
Lymphoma, Non-Hodgkin
Cutaneous Lymphoma
Cutaneous T Cell Lymphoma
Mycosis Fungoides
Sezary Syndrome
Drug: Brentuximab vedotin

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Exploratory Pilot Study of Brentuximab Vedotin (SGN-35) in Patients With Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Objective clinical response rate assessed by the standard response criteria used in MF (Mycosis fungoides) and SS (Sezary syndrome) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: June 2011
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SGN-35 arm Drug: Brentuximab vedotin
1.8 mg/kg; IV
Other Name: Adcetris

Detailed Description:

The purpose of this study is to learn the effects of an investigational medication, SGN 35, on patients with cutaneous T cell lymphoma (CTCL), specifically mycosis fungoides (MF) and Sezary syndrome (SS). Despite a wide range of therapeutic options, the treatments are associated with short response duration, thus this condition is largely incurable. This investigational drug may offer less toxicity than standard treatments and have better tumor specific targeting.

The primary objective is to explore the biologic activity of brentuximab vedotin (SGN-35) in patients with mycosis fungoides (MF) and Sézary syndrome (SS), the most common types of cutaneous T-cell lymphoma (CTCL), where expression of CD30 is variable. SGN-35 has significant biologic activity in Hodgkin's disease (HD) where only a small numbers of CD30 positive tumor cells are present, as well as in lymphomas with large numbers of CD30-expressing tumor cells such as systemic anaplastic large cell lymphoma (sALCL).

This phase II exploratory study will evaluate the clinical response of brentuximab vedotin (SGN-35) in MF and SS where tumor cells express variable levels of CD30 target molecule. The grouping by CD30 expression levels (low, intermediate, high) is for accrual purposes only to ensure a wide range of CD30 expression. Given the exploratory nature of this study, it will be open-label, single-arm, and non-randomized trial.

One centers will be involved to complete the accrual, a total of 24 patients with MF and SS. Enrollment will be based on CD30 expression levels by tissue immunohistochemistry (IHC), defined as low, intermediate or high expressers. The investigators will target 8 patients in each group for total of 24 patients. Of these 8 patients per group, up to 3 may be patients with SS.

Each patient regardless of CD30 expression level will receive 1.8 mg/kg of SGN-35 IV every 21 days, up to 8 cycles of therapy. Patients with CR may receive 2 additional cycles. Patients who have PR may receive up to a maximum of 16 doses IF they are continuing to improve after 8 cycles. Patients who relapse within 6 months after CR maybe eligible for retreatment.

  Eligibility

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

Inclusion Criteria:

  1. Patient has biopsy-proven MF/SS, stage IB-IVB, and failed one standard systemic therapy.

    • Skin biopsy will be obtained within 3 months of beginning study medication, for assessment of CD30 expression by immunohistochemistry (IHC). This data will be used to ensure equal enrollment of patients in the 3 groups of varying CD30 expression (low, intermediate, high). If patient has different lesion morphology (patch, plaque, tumor), a biopsy will be obtained from each morphologic lesion. If the patient has one type of lesion morphology, a biopsy from 2 separate anatomic sites will be obtained.
    • The highest CD30 expression value among biopsies will be used to determine which of the 3 groups the subject will be assigned to.
  2. Patients must have the following minimum wash-out from previous treatments:

    • >= 3 weeks for local radiation therapy, systemic cytotoxic anticancer therapy, treatment with other anti-cancer investigational agents (including monoclonal antibody).
    • > 3 weeks for retinoids, interferons, vorinostat, romidepsin, denileukin diftitox.
    • > 3 wks for phototherapy.
    • > 2 wks for topical therapy (including topical steroid, retinoid, nitrogen mustard, or imiquimod).
  3. At least 18 years of age.
  4. ECOG performance status of <= 2.
  5. Patients must be available for study treatment, blood sampling, study assessments, and management of toxicity at the treating institution.
  6. Adequate baseline laboratory data: absolute neutrophil count (ANC) >= 1000/uL, platelets >= 50,000/uL, bilirubin <= 2X upper limit of normal (ULN) or <= 3X ULN for patients with Gilbert's disease, serum creatinine <= 2X ULN, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 3X ULN.
  7. Women of childbearing potential (WOCBP) must have a negative serum beta-HCG pregnancy test result within seven days of treatment.
  8. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Patients with mycosis fungoides (MF) with limited disease (stage IA) or central nervous system (CNS) disease.
  2. Concomitant corticosteroid use, systemic or topical, for treatment of skin disease. Oral prednisone is allowed at <= 10 mg/day, if patient has been on a stable dose for at least 1 month prior to study entry.
  3. Patients with known Grade 3 or higher (per NCI CTCAE v4.0 criteria) active systemic or cutaneous viral, bacterial, or fungal infection.
  4. Patients who are known to be Hepatitis B or Hepatitis C antibody positive.
  5. Patients who are HIV-positive, and have a measurable viral load while on antiretrovirals.
  6. Patients with a known hypersensitivity to recombinant proteins or any excipient contained in the drug formulation.
  7. Patients with a history of other malignancies during the past three years. (The following are exempt from the three-year limit: non-melanoma skin cancer, curatively treated localized prostate cancer, curatively treated localized breast cancer, resected thyroid cancer, cervical intraepithelial neoplasia or cervical carcinoma in situ on biopsy).
  8. Patients who are currently pregnant or breastfeeding.
  9. Patients with congestive heart failure, Class III or IV, by New York Heart Association (NYHA) criteria.
  10. Patients with any serious underlying medical condition that would impair their ability to receive or tolerate the planned treatment.
  11. Patients with dementia or altered mental status that would preclude understanding and rendering of informed consent.
  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: NCT01396070

Contacts
Contact: Kokil Bakshi (650) 421-6370 kbakshi@stanford.edu

Locations
United States, California
Stanford University School of Medicine Recruiting
Stanford, California, United States, 94305
Contact: Kokil Bakshi    650-421-6370    kbakshi@stanford.edu   
Contact: Cancer Clinical Trials Office    (650) 498-7061    ccto-office@stanford.edu   
Principal Investigator: Youn H Kim         
Sub-Investigator: Alex McMillan         
Sub-Investigator: Ranjana Hira Advani         
Sub-Investigator: Randall Armstrong         
Sub-Investigator: Richard T. Hoppe         
Sub-Investigator: Dr. Christina S. Kong         
Sub-Investigator: Vijaya Bharathi Lingala         
Sub-Investigator: Sunil Arani Reddy         
Sub-Investigator: Uma Sundram         
Sub-Investigator: Wen-Kai Weng         
Sponsors and Collaborators
Youn Kim
Seattle Genetics, Inc.
Investigators
Principal Investigator: Youn H Kim Stanford University
  More Information

No publications provided

Responsible Party: Youn Kim, Professor, Stanford University
ClinicalTrials.gov Identifier: NCT01396070     History of Changes
Other Study ID Numbers: LYMNHL0089, SU-06212011-7946
Study First Received: July 14, 2011
Last Updated: July 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Mycoses
Mycosis Fungoides
Sezary Syndrome
Syndrome
Disease
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Antibodies, Monoclonal
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014