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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Non-Hodgkin Lymphoma (NHL), Cutaneous Lymphoma, Cutaneous T-cell Lymphoma (CTCL), Mycosis Fungoides, Sezary Syndrome

Intervention / Treatment
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* Drug: Brentuximab vedotin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brentuximab vedotin<br>Novel antibody-drug conjugate, 1.8 mg/kg intravenously every 3 weeks | Drug: Brentuximab vedotin<br>* 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.<br>* Other names: SGN-35;|

What is the study measuring?
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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 |