Clinical Trial: TSEB and Brentuximab for Treatment of Mycosis Fungoides & Sezary Syndrome

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase 1B Trial: Evaluation of the Safety of Adding Brentuximab Vedotin to Low-Dose Total Skin Electron Beam (TSEB) for Treatment of Patients With Mycosis Fungoides and Sézar

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.

Detailed Summary:

This study is a 2-cohort, open-label, phase 1B trial to evaluate the cutaneous toxicity, overall toxicity, and treatment response associated with administering concurrent low-dose TSEB and brentuximab vedotin in patients with mycosis fungoides or Sézary Syndrome. Duration of complete skin response, DOCB, and tumor response in lymph nodes and blood will also be evaluated. Additionally, skin-related QOL and neurotoxicity will be assessed.

Patients will be enrolled in 1 of 2 cohorts based on disease stage.

Cohort A will include patients with earlier stage disease (selected Stage IB in patients who have had one previous course of low-dose TSEB) and Stages IIA through IIIA [if N0-1]).

Cohort B will include patients with more advanced disease (Stage IIA through IIIA [if N2-3], Stage IIIB, Stage IVA, and transformed CTCL) who are candidates for low-dose TSEB and/or systemic therapy.

A standard dose of brentuximab vedotin will be administered to all patients by intravenous infusion 3 weeks prior to initiation of low-dose TSEB and then every 3 weeks for a total of 3 cycles. Cohort A patients will complete brentuximab vedotin after 3 cycles; patients in Cohort B will continue brentuximab vedotin until disease progression or unacceptable toxicity, whichever occurs first. In the absence of progression or unacceptable toxicity, the patient may receive brentuximab vedotin for up to 2 years as a study participant. A total of 12 Gy TSEB (ie, low-dose TSEB) will be administered to both cohorts per standard protocol in 6 fractions (2 fractions per week) beginning 3 weeks after the first dose of brentuximab vedotin.

The Modified Severity Weighted Assessment Tool (mSWAT) (16), completed by
Sponsor: Virginia Commonwealth University

Current Primary Outcome:

• Cutaneous toxicity of combining TSEB and brentuximab vedotin in patients with MF or SS (Cohorts A and B). [ Time Frame: 6 months ]
  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
• Number of patients who achieved Complete Response (CR) and Partial Response(PR) [ Time Frame: 2 years ]
  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.

Original Primary Outcome:

• Cutaneous toxicity of combining TSEB and brentuximab vedotin in patients with MF or SS (Cohorts A and B). [ Time Frame: 3 months ]
  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
• Number of patients who achieved Complete Response (CR) and Partial Response(PR) [ Time Frame: 2 years ]
  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.

Current Secondary Outcome:

• Duration of complete skin response (Cohorts A and B) [ Time Frame: 2 years ]
  Duration of skin response defined as the time from first determination of CR until relapse in the skin based on mSWAT assessment.
• Tumor response in lymph nodes (Cohort B) [ Time Frame: 6 months ]
  Tumor response in lymph nodes for patients with N2 or N3 disease at baseline.
• Tumor response in blood (Cohort B) [ Time Frame: 6 months ]
  Tumor response in blood for patients with B1 or B2 disease at baseline.
• Overall Toxicity (Cohorts A and B) [ Time Frame: 2 years ]
  AEs reported using criteria in the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) and AEs defined in the protocol.
• Skin-related Quality of Life (QOL) (Cohorts A and B) [ Time Frame: 2 years ]
  Patient responses to questions on Skindex-16 (standardized assessment measures for patients with skin disease) that will be administered at baseline and at 2, 4, 10, and 16 weeks following completion of TSEB
• Patient-reported chemotherapy-induced peripheral neuropathy (CIPN) (Cohort A) [ Time Frame: 2 years ]
  Patient responses to questions on Form NTX (standardized patient-completed assessment tool to evaluate CIPN) that will be administered at baseline and at 2, 4, 10, and 16 weeks following completion of TSEB.
• Duration of clinical benefit (DOCB) [ Time Frame: 2 years ]
  DOCB defined as the time from initial response until any total skin-equivalent treatment (eg, topical treatment to > 50% of body surface, phototherapy, second TSEB treatment) or systemic therapy is initiated, or until disease progression.

Original Secondary Outcome:

• Duration of complete skin response (Cohorts A and B) [ Time Frame: 2 years ]
  Duration of skin response defined as the time from first determination of CR until relapse in the skin based on mSWAT assessment.
• Tumor response in lymph nodes (Cohort B) [ Time Frame: 2 years ]
  Tumor response in lymph nodes for patients with N2 or N3 disease at baseline.
• Tumor response in blood (Cohort B) [ Time Frame: 2 years ]
  Tumor response in blood for patients with B1 or B2 disease at baseline.
• Progression-free survival (PFS) (Cohorts A and B) [ Time Frame: 2 years ]
  PFS defined as the time from initiation of study treatment until disease progression or death, whichever occurs first
• Skin-related Quality of Life (QOL) (Cohorts A and B) [ Time Frame: 2 years ]
  Patient responses to questions on Skindex-16 (standardized assessment measures for patients with skin disease) that will be administered at baseline and at 2, 4, 10, and 16 weeks following completion of TSEB
• Patient-reported chemotherapy-induced peripheral neuropathy (CIPN) (Cohorts A and B) [ Time Frame: 2 years ]
  Patient responses to questions on Form NTX (standardized patient-completed assessment tool to evaluate CIPN) that will be administered at baseline and at 2, 4, 10, and 16 weeks following completion of TSEB.

Information By: Virginia Commonwealth University

Dates:
Date Received: June 30, 2016
Date Started: December 19, 2016
Date Completion: October 31, 2020
Last Updated: May 3, 2017
Last Verified: May 2017