This phase Ib/II trial investigates the side effects of mogamulizumab and extracorporeal photopheresis and to see how well they work in treating patients with Sezary syndrome or mycosis fungoides. Mogamulizumab (a humanized antibody) binds to CCR4, a protein often found in high amounts on T-cell lymphoma cells. Binding to these cells may slow their growth, as well as mark them for attack by the immune system. Extracorporeal photopheresis (ECP) is a standard treatment for cancers that affects the skin, and may work by killing some lymphoma cells directly and by boosting the body's immune response against other lymphoma cells. Giving mogamulizumab together with ECP may work better in treating patients with Sezary syndrome or mycosis fungoides compared to either therapy alone.
PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of the combination of mogamulizumab and ECP in Sezary syndrome (SS) and erythrodermic mycosis fungoides (MF). II. To determine the efficacy of the combination of mogamulizumab and extra-corporeal photopheresis in SS and erythrodermic MF. SECONDARY OBJECTIVE: I. To assess response by disease compartment, time to response, duration of response, progression free survival (PFS), and change in quality of life in patients with Sezary syndrome and erythrodermic MF treated with mogamulizumab and ECP. TERTIARY/EXPLORATORY OBJECTIVE: I. To assess biomarkers of response and changes in immunologic response on serial blood samples and peripheral blood flow cytometry. OUTLINE: INDUCTION (WEEKS 1-7): Patients receive mogamulizumab intravenously (IV) over 60 minutes on days 1, 8, 15, 22, and 36 in the absence of disease progression progression and unacceptable toxicity. Patients also undergo extracorporeal photopheresis on days 1, 8, 15, 22, 29, and 36 in the absence of disease progression and unacceptable toxicity. TREATMENT (CYCLES 1-12): Patients receive mogamulizumab IV over 60 minutes on days 1 and 15, and undergo extracorporeal photopheresis on days 1 and 15 of cycles 1-6, then day 1 of subsequent cycles. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression and unacceptable toxicity. MAINTENANCE (CYCLES 13+): Patients with clinical benefit may continue extracorporeal photopheresis on day 1. Cycles repeat every 28 days in the absence of disease progression and unacceptable toxicity. After completion of study treatment, patients are followed up for 90 days, then every 3 months for 3 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
5
Emory University Hospital
Atlanta, Georgia, United States
Frequency of dose-limiting toxicities (DLT's) (Phase Ib)
Descriptive statistics (n, frequency and percentage) of toxicities and number of DLT's during the DLT window per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be reported. Corresponding listings of data will be generated. DLT rate will be calculated as proportion (Patients with DLT/Total patients) along with 95% confidence intervals using the Clopper-Pearson method.
Time frame: Up to 6 weeks
Rate of overall response lasting at least 6 months (ORR6) (Phase II)
Assessed using the Global Response Score (GRS). ORR6 rate will be determined by dividing the number of ORR6's by the total number of evaluable patients. Will be calculated as proportion (Responders/Total patients) along with 95% confidence intervals using the Clopper-Pearson method. Chi-square test or Fisher's exact test will be used to compare the efficacy in term of response rate between the different groups stratified by baseline factors, respectively. Logistic regression model will be further employed to test the adjusted effect of dosage on the response rate after adjusting for other clinical factors and demographic factors.
Time frame: Up to 3 years post treatment
Best overall response rate (ORR)
Assessed using the Global Response Score (GRS), which consists of skin evaluation (modified severity weighted assessment tool \[mSWAT\]), radiographic assessment, and detection of circulating Sezary cells on flow cytometry in patients that have received at least 1 month of combined therapy. Overall response, complete response, and partial response will be calculated as proportions along with 95% confidence intervals using the Clopper-Pearson method.
Time frame: Up to 3 years post treatment
Duration of response (DOR)
Based on GRS. Defined as time from the date when criteria for response (complete response \[CR\] or partial response \[PR\]) based on GRS was first met until the date when the response was first lost (date of loss is date when first meets criteria for progressive disease \[PD\] or death). Will be estimated using the Kaplan-Meier method.
Time frame: Up to 3 years post treatment
Time to response (TTR)
Based on GRS. Defined as time from the date of first dosing to the date when criteria for response (CR or PR) based on GRS are first met. Will be estimated using the Kaplan-Meier method.
Time frame: Up to 3 years post treatment
Overall survival (OS)
Estimated by Kaplan-Meier method. Cox proportional hazards models will be further used in the multivariable analyses to assess the patients' OS after adjusting for other factors. Interaction terms between these factors will also be tested for statistical significance. The proportional hazards assumption will be evaluated graphically and analytically with regression diagnostics. Violations of the proportional hazards assumptions will be addressed by use of time-dependent covariates or extended Cox regression models.
Time frame: Date of 1st dose of study drug to death from any cause, assessed up to 3 years
Progression free survival (PFS)
Estimated by Kaplan-Meier method. Cox proportional hazards models will be further used in the multivariable analyses to assess the patients' PFS after adjusting for other factors. Interaction terms between these factors will also be tested for statistical significance. The proportional hazards assumption will be evaluated graphically and analytically with regression diagnostics. Violations of the proportional hazards assumptions will be addressed by use of time-dependent covariates or extended Cox regression models.
Time frame: Date of 1st dose of study drug to progression, death, or subsequent systemic anti-cancer therapy, assessed up to 3 years
Incidence of adverse events
Adverse events (AEs) will be listed and summarized. Adverse events will also be listed by severity, seriousness, and by system organ class. Will also evaluate toxicities which will be presented in tabular form as appropriate based on grade and attribution. The number and percentage of subjects who experience AEs will be presented in tabular and/or graphical format and summarized descriptively, where appropriate AEs will be presented with and without regard to causality based on the investigator's judgment. The frequency of overall toxicity, categorized by toxicity grades 1 through 5, will be described. Additional summaries will be provided for AEs that are observed with higher frequency.
Time frame: Up to 3 years post treatment
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