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 Sézary Syndrome
Overview
- Phase
- Phase 1
- Intervention
- TSEB Therapy
- Conditions
- Mycosis Fungoides
- Sponsor
- Virginia Commonwealth University
- Enrollment
- 5
- Locations
- 1
- Primary Endpoint
- Cutaneous toxicity of combining TSEB and brentuximab vedotin in patients with MF or SS (Cohorts A and B).
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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 Description
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 therapy) 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 the investigator, will be used to determine skin involvement at baseline and skin response to treatment beginning after administration of the 3 doses of brentuximab vedotin and low-dose TSEB. Skindex-16, a patient-completed form that measures symptoms and perceptions of toxicity in patients with skin disease will be used to assess skin-related QOL. Additionally, Form NTX will be completed by patients in Cohort A to assess symptoms of CIPN which is a side effect of brentuximab vedotin. The sample size for this study will be a maximum of 15 patients for a total of 12 evaluable patients with no more than 6 patients in Cohort B. However, if the number of patients with severe toxicity exceeds the established acceptable incidence, accrual will end before reaching the sample size goal of 12 evaluable patients.
Investigators
Eligibility 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:
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
- •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.
Arms & Interventions
Cohort A (Stage IB and Stage IIA to IIIB [if N0-1])
(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.
Intervention: TSEB Therapy
Cohort A (Stage IB and Stage IIA to IIIB [if N0-1])
(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.
Intervention: Brentuximab vedotin
Cohort B(Stage IIA to IIIB; IVA;transformed CTCL)
(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).
Intervention: TSEB Therapy
Cohort B(Stage IIA to IIIB; IVA;transformed CTCL)
(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).
Intervention: Brentuximab vedotin
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Overall Toxicity (Cohorts A and B)(2 years)
- 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)
- Skin-related Quality of Life (QOL) (Cohorts A and B)(2 years)
- Duration of clinical benefit (DOCB)(2 years)
- Patient-reported chemotherapy-induced peripheral neuropathy (CIPN) (Cohort A)(2 years)