Mogamulizumab and Extracorporeal Photopheresis for the Treatment of Sezary Syndrome or Mycosis Fungoides
Hematopoietic Malignancies
Leukemia
Lymphoma
Non-Hodgkin Lymphoma
Unknown Primary
18 Years and older, Male and Female
WINSHIP5101-20 (primary)
NCI-2020-06013
Summary
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.
Objectives
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 1-6): Patients receive mogamulizumab intravenously (IV) over 60 minutes on days 1, 8, 15, 22, and 29 for 5 weeks in the absence of disease 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): Beginning 1 week after induction, 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+): Beginning 2 weeks after cycle 12, 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.
Eligibility
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Histopathologic diagnosis of primary cutaneous T-cell non-Hodgkin lymphoma (CTCL) (mycosis fungoides [MF] or Sezary syndrome [SS]), confirmed by skin biopsy, or lymph node, or blood assessment, of current disease
- CTCL stage 3A-4A2 disease at study entry according to International Society of Cutaneous Lymphoma (ISCL)/European Organization for Research and Treatment of Cancer (EORTC)
- Newly diagnosed or =< 3 different lines of systemic therapy
* Systemic therapy includes oral retinoids, interferon, pralatrexate, methotrexate, vorinostat, romidepsin, or other oral, IV or subcutaneous treatments used to treat systemic disease
* A line of therapy is defined as any therapy or group of therapies that was started or changed for lack of response, disease progression, or intolerance
- A minimum washout period of 4 weeks after previous CTCL therapy is recommended prior to the first dose of combination therapy
- Willing and able to comply with all aspects of the protocol
- Absolute neutrophil count (ANC) >= 500/mcL (within 16 days of cycle 1 day 1)
- Platelets >= 50,000/mcL (within 16 days of cycle 1 day 1)
- Total bilirubin =< 3 institutional upper limit of normal (ULN) (within 16 days of cycle 1 day 1)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 5 institutional upper limit of normal (ULN) (within 16 days of cycle 1 day 1)
- Not dialysis dependent, creatinine clearance >= 30 mL/min (within 16 days of cycle 1 day 1)
- Female of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting therapy: documented by negative beta-human chorionic gonadotropin [beta-hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of beta-hCG. A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug
- FCBP and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 30 Days after completion. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 30 days after completion of study drug administration. A female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months
**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts...
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