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

• ClinicalTrials.gov Identifier: NCT01396070
• Recruitment Status: Completed
• First Posted: July 18, 2011
• Results First Posted: April 5, 2017
• Last Update Posted: April 5, 2017
• Sponsor: Youn Kim
• Collaborator: Seagen Inc.
• Information provided by (Responsible Party): Youn Kim, Stanford University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Non-Hodgkin Lymphoma (NHL); Cutaneous Lymphoma; Cutaneous T-cell Lymphoma (CTCL); Mycosis Fungoides; Sezary Syndrome	Drug: Brentuximab vedotin	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: May 2011
• Actual Primary Completion Date: April 2015
• Actual Study Completion Date: May 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Overall Response Rate (ORR) [ Time Frame: 2 years ]
   Overall response rate of brentuximab vedotin in this study population.

Secondary Outcome Measures :

1. Overall Stable Disease Rate [ Time Frame: 2 years ]

   Overall Stable Disease Rate (SD) in this study population.

   3 subjects were not evaluable.

2. Overall Partial Response Rate [ Time Frame: 2 years ]

   Overall Partial Response Rate (PR) in this study population.

   3 subjects were not evaluable.

3. Overall Non-Evaluable Response [ Time Frame: 4 weeks ]

   Overall Non-Evaluable Response of full patient population

   3 subjects were not evaluable.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

Stanford University School of Medicine

Stanford, California, United States, 94305

Sponsors and Collaborators

Youn Kim

Seagen Inc.

Investigators

• Principal Investigator: Youn H Kim; Stanford University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Youn Kim, The Joanne and Peter Haas, Jr, Professor for Cutaneous Lymphoma Research, Stanford University
• ClinicalTrials.gov Identifier: NCT01396070
• Other Study ID Numbers: IRB-21324; LYMNHL0089 ( Other Identifier: OnCore ); SU-06212011-7946 ( Other Identifier: Stanford University )
• First Posted: July 18, 2011
• Results First Posted: April 5, 2017
• Last Update Posted: April 5, 2017
• Last Verified: February 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Mycoses; Lymphoma; Lymphoma, Non-Hodgkin; Mycosis Fungoides; Sezary Syndrome; Lymphoma, T-Cell, Cutaneous; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, T-Cell; Bacterial Infections and Mycoses; Infections; Brentuximab Vedotin; Antineoplastic Agents, Immunological; Antineoplastic Agents