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

NCT ID: NCT01396070

Last Updated: 2017-04-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2016-05-31

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Brentuximab vedotin

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

Group Type: EXPERIMENTAL

Brentuximab vedotin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Adcetris; SGN-35

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Seagen Inc.

INDUSTRY

Sponsor Role: collaborator

Youn Kim

OTHER

Sponsor Role: lead

Responsible Party

Youn Kim

The Joanne and Peter Haas, Jr, Professor for Cutaneous Lymphoma Research

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Youn H Kim

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 26195720 (View on PubMed)

Other Identifiers

LYMNHL0089

Identifier Type: OTHER

Identifier Source: secondary_id

SU-06212011-7946

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-21324

Identifier Type: -

Identifier Source: org_study_id