TSEB and Brentuximab for Treatment of Mycosis Fungoides & Sezary Syndrome

NCT02822586 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: MCC-15-10917IST2015100830NCI-2016-01509
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Mycosis Fungoides; Sézary Syndrome

Keywords

CD30-positive; Stage IB to Stage IVA

Outcome Measures

Primary Outcomes (2)

• Cutaneous toxicity of combining TSEB and brentuximab vedotin in patients with MF or SS (Cohorts A and B).

  Selected cutaneous adverse events (AEs) that occurred during treatment or during the 3 months following initiation of study treatment and that are characterized and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI CTCAE v4.0) including ≥ grade 3 AEs and selected grade 2 AEs

  6 months

• Number of patients who achieved Complete Response (CR) and Partial Response(PR)

  Number of patients who have achieved cutaneous CR to treatment defined as 100% clearance of skin lesions or cutaneous partial response (PR) defined as 50%-99% clearance of skin disease from baseline without new tumors in patients with T1-, T2-, or T4-only skin disease.

  2 years

Secondary Outcomes (7)

• Duration of complete skin response (Cohorts A and B)

  2 years

• Tumor response in lymph nodes (Cohort B)

  6 months

• Tumor response in blood (Cohort B)

  6 months

• Overall Toxicity (Cohorts A and B)

  2 years

• Skin-related Quality of Life (QOL) (Cohorts A and B)

  2 years

Study Arms (2)

Cohort A (Stage IB and Stage IIA to IIIB [if N0-1])

EXPERIMENTAL

(Eligible patients with Stage IB, IIA, IIB, and IIIA \[if N0-1\]) Brentuximab Vedotin 1.8 mg/kg IV every 3 weeks for 3 doses beginning 3 weeks prior to initiation of TSEB. TSEB 12 Gy in 6 fractions at 2 Gy/fraction treated twice/week.

Radiation: TSEB Therapy; Drug: Brentuximab vedotin

Cohort B(Stage IIA to IIIB; IVA;transformed CTCL)

EXPERIMENTAL

(Eligible patients with Stage IIA, IIB, IIIA \[if N2-3\]; IIIB; Stage IVA; and transformed CTCL) Brentuximab Vedotin 1.8 mg/kg IV every 3 weeks for 3 doses beginning 3 weeks prior to initiation of TSEB. TSEB 12 Gy in 6 fractions at 2 Gy/fraction treated twice/week. Continuation of brentuximab every 3 weeks until disease progression or unacceptable toxicity or for up to 2 years as a study participant, (whichever occurs first).

Radiation: TSEB Therapy; Drug: Brentuximab vedotin

Interventions

TSEB Therapy RADIATION

TSEB is a type of radiation treatment in which the skin over the whole body is treated with electron radiation beams. All participants will receive the same standard TSEB dose and treatment schedule. During TSEB, patients are treated in a standing position on a rotating platform.

Also known as: total skin electron beam, TSEB

Cohort A (Stage IB and Stage IIA to IIIB [if N0-1]); Cohort B(Stage IIA to IIIB; IVA;transformed CTCL)

Brentuximab vedotin DRUG

An antibody-drug conjugate (ADC) that targets CD30. A standard dose of brentuximab vedotin will be administered to all patients by intravenous infusion 3 weeks prior to initiation of TSEB and then every 3 weeks for 3 cycles.

Also known as: Adcetris

Cohort A (Stage IB and Stage IIA to IIIB [if N0-1]); Cohort B(Stage IIA to IIIB; IVA;transformed CTCL)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• Seagen Inc.: collaborator

Study Sites (1)

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Mycosis Fungoides; Sezary Syndrome

Interventions

Brentuximab Vedotin

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• Shiyu Song, M.D., Ph.D.

  Massey Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2016
• First Posted: July 4, 2016
• Study Start: December 19, 2016
• Primary Completion: April 29, 2019
• Study Completion: April 29, 2019
• Last Updated: August 30, 2019

Record last verified: 2019-08

Locations

US (1)