Brentuximab Vedotin (SGN-35) in Patients With Mycosis Fungoides With Variable CD30 Expression Level

Exploratory Pilot Study of Brentuximab Vedotin (SGN-35) in Patients With Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level

The purpose of this study is to learn the effects of brentuximab vedotin (SGN-35), an investigational medication, 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.

Study Overview

• Status: Completed
• Conditions: Mycosis Fungoides; Sezary Syndrome; Cutaneous T-cell Lymphoma (CTCL); Cutaneous Lymphoma; Non-Hodgkin Lymphoma (NHL)
• Intervention / Treatment: Drug: Brentuximab vedotin

Detailed Description

This phase 2 exploratory study will evaluate the clinical response of brentuximab vedotin in MF and SS, where tumor cells express variable levels of CD30 target molecule.

The primary objective is to explore the biologic activity of brentuximab vedotin in patients with MF and SS, the most common types of cutaneous T-cell lymphoma (CTCL), where expression of CD30 is variable. Brentuximab vedotin 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). The subject grouping by CD30 expression levels (low, intermediate, high) is for accrual purposes only, to ensure that a wide range of CD30 expression is studied.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Biopsy-proven MF/SS, stage IB-IVB, and failed one standard systemic therapy. Skin biopsy must be within 3 months of beginning study medication

• At least the following wash-out from prior 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 and phototherapy
  • > 2 wks for topical therapy (including topical steroid, retinoid, nitrogen mustard, or imiquimod)
• At least 18 years of age
• ECOG performance status of ≤ 2
• Must be able to commit to study schedule
• Absolute neutrophil count (ANC) ≥ 1000/uL
• Platelets ≥ 50,000/uL
• Bilirubin ≤ 2X upper limit of normal (ULN) (EXCEPTION: Gilbert's disease ≤ 3X ULN)
• Serum creatinine ≤ 2X ULN
• Alanine aminotransferase (ALT) ≤ 3X ULN
• Aspartate aminotransferase (AST) ≤ 3X ULN
• Negative serum beta-HCG pregnancy test result within 7 days of first treatment, if a woman of childbearing potential
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Mycosis fungoides (MF) with limited disease (stage IA) or central nervous system (CNS) disease
• Systemic or topical concomitant corticosteroid use for treatment of skin disease (EXCEPTION: Oral prednisone allowed at ≤ 10 mg/day)
• Known Grade 3 or higher (per NCI CTCAE v4.0 criteria) active systemic or cutaneous viral, bacterial, or fungal infection
• Known to be Hepatitis B or Hepatitis C antibody positive
• HIV-positive with have a measurable viral load while on antiretroviral medication
• Known hypersensitivity to recombinant proteins or any excipient contained in the drug formulation.
• History of other malignancies during the past 3 years (EXCEPTIONS: 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).
• Pregnant
• Breastfeeding
• Congestive heart failure, Class III or IV, by New York Heart Association (NYHA) criteria.
• Any serious underlying medical condition that would impair subject's ability to receive or tolerate the planned treatment.
• Dementia or altered mental status that would preclude subject's understanding and rendering of informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Brentuximab vedotin; Novel antibody-drug conjugate, 1.8 mg/kg intravenously every 3 weeks	Drug: Brentuximab vedotin; 1.8 mg/kg by IV every 3 weeks for a maximum of 16 doses (8 cycles). Brentuximab vedotin is an antibody conjugate, consisting of the chimeric IgG1 anti-CD30 antibody cAC10; the microtubule disrupting agent monomethyl auristatin E (MMAE); a protease-cleavable linker that covalently attaches MMAE to cAC10.; Other Names: Adcetris; SGN-35

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Overall response rate of brentuximab vedotin in this study population.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Stable Disease Rate	Overall Stable Disease Rate (SD) in this study population. 3 subjects were not evaluable.	2 years
Overall Partial Response Rate	Overall Partial Response Rate (PR) in this study population. 3 subjects were not evaluable.	2 years
Overall Non-Evaluable Response	Overall Non-Evaluable Response of full patient population 3 subjects were not evaluable.	4 weeks

Collaborators and Investigators

• Sponsor: Youn Kim
• Collaborators: Seagen Inc.
• Investigators: Principal Investigator: Youn H Kim, Stanford University

Publications and helpful links

General Publications

• Kim YH, Tavallaee M, Sundram U, Salva KA, Wood GS, Li S, Rozati S, Nagpal S, Krathen M, Reddy S, Hoppe RT, Nguyen-Lin A, Weng WK, Armstrong R, Pulitzer M, Advani RH, Horwitz SM. Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sezary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project. J Clin Oncol. 2015 Nov 10;33(32):3750-8. doi: 10.1200/JCO.2014.60.3969. Epub 2015 Jul 20.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (ACTUAL): April 1, 2015
• Study Completion (ACTUAL): May 1, 2016

Study Registration Dates

• First Submitted: July 14, 2011
• First Submitted That Met QC Criteria: July 15, 2011
• First Posted (ESTIMATE): July 18, 2011

Study Record Updates

• Last Update Posted (ACTUAL): April 5, 2017
• Last Update Submitted That Met QC Criteria: February 17, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Bacterial Infections and Mycoses; Lymphoma, T-Cell; Lymphoma; Lymphoma, Non-Hodgkin; Mycoses; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome; Antineoplastic Agents; Antineoplastic Agents, Immunological; Brentuximab Vedotin
• Other Study ID Numbers: IRB-21324; LYMNHL0089 (OTHER: OnCore); SU-06212011-7946 (OTHER: Stanford University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO