Clinical trial NCT01396070: Brentuximab Vedotin (SGN-35) in Patients With Mycosis Fungoides With Variable CD30 Expression Level
Official title: Exploratory Pilot Study of Brentuximab Vedotin (SGN-35) in Patients With Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Hodgkin Lymphoma (NHL)
Cutaneous Lymphoma
Cutaneous T-cell Lymphoma (CTCL)
Mycosis Fungoides
Sezary Syndrome
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Seagen Inc.
First posted: 2011-07-18
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: 2 years
Secondary outcomes:
measure: Overall Stable Disease Rate
timeFrame: 2 years
measure: Overall Partial Response Rate
timeFrame: 2 years
measure: Overall Non-Evaluable Response
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Youn H Kim
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.