TSEB and Brentuximab for Treatment of Mycosis Fungoides & Sezary Syndrome

This is an interventional treatment trial for Mycosis Fungoides focused on measuring CD30-positive, Stage IB to Stage IVA Read More

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