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

• Sponsor: Youn Kim
• Collaborator: Seattle Genetics, Inc.
• Information provided by (Responsible Party): Youn Kim, Stanford University

Tracking Information

• First Submitted Date: July 14, 2011
• First Posted Date: July 18, 2011
• Results First Submitted Date: December 28, 2016
• Results First Posted Date: April 5, 2017
• Last Update Posted Date: April 5, 2017
• Study Start Date: May 2011
• Actual Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 17, 2017)

Overall Response Rate (ORR) [ Time Frame: 2 years ]

Overall response rate of brentuximab vedotin in this study population.

• Original Primary Outcome Measures (submitted: July 15, 2011): Objective clinical response rate assessed by the standard response criteria used in MF (Mycosis fungoides) and SS (Sezary syndromel) [ Time Frame: 4 weeks ]
• Change History: Complete list of historical versions of study NCT01396070 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: February 17, 2017)

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

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

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

Study Arms

Experimental: Brentuximab vedotin

Novel antibody-drug conjugate, 1.8 mg/kg intravenously every 3 weeks

Intervention: Drug: Brentuximab vedotin

• 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 Sézary 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 9, 2014): 36
• Original Estimated Enrollment (submitted: July 15, 2011): 18
• Actual Study Completion Date: May 2016
• Actual Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01396070
• Other Study ID Numbers: IRB-21324; LYMNHL0089 ( Other Identifier: OnCore ); SU-06212011-7946 ( Other Identifier: Stanford University )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Youn Kim, Stanford University
• Study Sponsor: Youn Kim
• Collaborators: Seattle Genetics, Inc.

Investigators

• Principal Investigator: Youn H Kim; Stanford University

• PRS Account: Stanford University
• Verification Date: February 2017