TSEB and Brentuximab for Treatment of Mycosis Fungoides & Sezary Syndrome

• Status: Completed
• Trial end date: 2019-04-29
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to evaluate the cutaneous toxicity and treatment response associated with administering concurrent TSEB and brentuximab vedotin in patients with mycosis fungoides or Sézary Syndrome.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Virginia Commonwealth University
• Collaborators: Seagen Inc.; Seattle Genetics, Inc.
• Treatments: Antibodies, Monoclonal; Brentuximab Vedotin

Criteria

Inclusion Criteria:

• Histologically confirmed CD30-positive (defined in this study as ≥ 1% expression) Mycosis Fungoides (including large cell transformation variant) or Sezary Syndrome who have either:

• Received prior systemic therapy (for whom commercial supply of brentuximab vedotin is available) OR

• Not received prior systemic therapy (who will receive brentuximab vedotin free of charge)

• Any of the disease stages listed below

• Stage IB disease that meets one of the following criteria:

• Plaque disease (ie,T2b staging)

• Diffuse skin involvement with indication for TSEB (plaque disease with or without patches)

• Not appropriate for treatment with focal therapies

• One prior course of low-dose TSEB or one prior course of systemic chemotherapy regimens (excluding brentuximab)

• Stage IIA, IIB, or IIIA that meets ONE or BOTH of the following criteria:

• Patient is a candidate for treatment with low-dose TSEB

• Patient is a candidate for systemic therapy

• IIIB or IVA disease requiring systemic therapy

• Transformed CTCL

• Candidate for TSEB based on investigator determination

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2, or 3, if the performance status of 3 is due to skin disease involvement

• Adequate bone marrow function as defined below:

• Absolute neutrophil count (ANC) ≥ 1000/mm3

• Platelets > 75,000/mm3

• Hemoglobin ≥ 9 g/dL

• Note: Patients requiring transfusion to meet the hemoglobin requirement are not eligible for the study.

• Calculated creatinine clearance (CrCl) > 30 mL/min.

• Adequate hepatic function as defined below:

• Total bilirubin ≤ 1.5 x ULN for the laboratory

• Aspartate aminotransferase (AST) ≤ 2 x ULN for the laboratory

• Alanine aminotransferase (ALT) ≤ 2 x ULN for the laboratory

• Prothrombin time with INR ≤ ULN for the laboratory

• A woman of childbearing potential (WCBP), defined as a woman who is < 60 years of age and has not had a hysterectomy, must have a documented negative serum pregnancy test 14 days prior to study registration

• Note: If study treatment is not initiated within 7 days after the pregnancy test, the pregnancy test must be repeated.

• A WCBP and a male patient with a partner who is a WCBP must agree to use a medically accepted method for preventing pregnancy for the duration of study treatment and for at least 6 months following completion of study treatment

• Ability to understand and willingness to sign the consent form

Exclusion Criteria:

• Previous TSEB therapy with total dose > 20 Gy

• Previous brentuximab treatment

• Any of the following within 4-3 weeks prior to initiating study treatment

• Systemic biologic therapy

• Monoclonal antibody

• Chemotherapy

• TSEB

• Phototherapy

• Other investigational therapy

• Anticancer topical therapy, including therapeutic doses of steroids, within 2 weeks prior to initiating study treatment

• Note: Topical steroids at doses intended for symptom management are permitted prior to study enrollment and may continue during study treatment.

• Peripheral sensory neuropathy or peripheral motor neuropathy ≥ grade 2 per NCI CTCAE v4.0

• Diabetic neuropathy (any grade)

• Demyelinating form of Charcot-Marie-Tooth Syndrome

• History of progressive multifocal leukoencephalopathy

• Active or clinically significant cardiac disease including any of the following:

• Unstable angina (eg, anginal symptoms at rest) or onset of angina within 3 months prior to initiating study treatment

• Myocardial infarction within 6 months prior to initiating study treatment

• New York Heart Association (NYHA) class III or IV congestive heart failure (Appendix 4)

• Active ≥ grade 3 (per NCI CTCAE v4) viral, bacterial, or fungal infection within 2 weeks prior to initiation of study treatment

• Known human immunodeficiency virus (HIV) infection

• Known or suspected active hepatitis B or C infection

• Known cirrhosis

• Known Gilbert's Syndrome

• Planned ongoing treatment with another drug that may potentially have adverse interactions with brentuximab vedotin; if such a drug has been used, it must be discontinued at least 1 week prior to initiating study treatment (see Section 6.6); examples of potential interactions include:

• Coadministration of strong inhibitors of CYP3A4 (eg, ketoconazole, ritonavir, clarithromycin)

• Coadministration of CYP3A4 inducers (eg, rifampin)

• Concomitant treatment with strong inhibitors of P-glycoprotein (P-gp)

• Known hypersensitivity to any excipient contained in the brentuximab formulation

• Prior malignancy or myelodysplastic syndrome (active within 3 years of screening) except completely excised non-invasive basal cell or squamous cell carcinoma of the skin, and in situ squamous cell carcinoma of the cervix

• Pregnancy or breastfeeding

• Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements