Mogamulizumab and Extracorporeal Photopheresis for the Treatment of Sezary Syndrome or Mycosis Fungoides

NCT04676087 | Terminated Phase 1 DMC FDA Drug

• 4 other identifiers: STUDY00001265NCI-2020-06013WINSHIP5101-20P30CA138292
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Mycosis Fungoides; Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Sezary Syndrome

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Up to 3 years post treatment

Secondary Outcomes (6)

• Best overall response rate (ORR)

  Up to 3 years post treatment

• Duration of response (DOR)

  Up to 3 years post treatment

• Time to response (TTR)

  Up to 3 years post treatment

• Overall survival (OS)

  Date of 1st dose of study drug to death from any cause, assessed up to 3 years

• Progression free survival (PFS)

  Date of 1st dose of study drug to progression, death, or subsequent systemic anti-cancer therapy, assessed up to 3 years

Other Outcomes (3)

• Genomic and immunologic profiles

  Up to 3 years post treatment

• T cell populations will include T-regulatory cells and CD8+ cytotoxic T-cells

  Induction is 7 weeks. Treatment consists of 28 cycles (12). Maintenance resumes after 12 cycles with ECP on day 1 of each 28 day cycle.

• Changes in genomic profiles

  Induction is 7 weeks. Treatment consists of 28 cycles (12). Maintenance resumes after 12 cycles with ECP on day 1 of each 28 day cycle.

Study Arms (1)

Treatment (mogamulizumab, ECP)

EXPERIMENTAL

INDUCTION (WEEKS 1-7): Patients receive mogamulizumab 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.

Procedure: Extracorporeal Photopheresis; Biological: Mogamulizumab; Other: Quality-of-Life Assessment

Interventions

Extracorporeal Photopheresis PROCEDURE

Undergo ECP

Also known as: Extracorporeal Photophoresis, photopheresis, Photophoresis

Treatment (mogamulizumab, ECP)

Mogamulizumab BIOLOGICAL

Given IV

Also known as: Immunoglobulin G1, Anti-(CC Chemokine Receptor CCR4) (Human-Mouse Monoclonal KW-0761 Heavy Chain), Disulfide With Human-Mouse Monoclonal KW-0761 Kappa-Chain, Dimer, KM8761, KW-0761, Mogamulizumab-kpkc, Poteligeo

Treatment (mogamulizumab, ECP)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (mogamulizumab, ECP)

Eligibility Criteria

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

You may qualify if:

• 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, single or multi-agent chemotherapy 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
• Prior cytotoxic chemotherapy excluding low dose methotrexate
• 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
• Provide voluntary written informed consent prior to any study specific screening procedures
• 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)

You may not qualify if:

• Visceral involvement except for CTCL involvement of the bone marrow
• Bulky lymphadenopathy (\> 5 cm), or pathologically N3 lymph node involvement
• Total skin electron beam therapy within 6 months prior to registration
• Prior allogeneic transplantation
• Prior mogamulizumab therapy within 6 months of registration or progression or intolerance of mogamulizumab
• Patients with 2 or less doses of prior mogamulizumab prior to registration will be eligible regardless of date mogamulizumab was received
• Patients who received mogamulizumab pre-study enrollment would restart day 1 dosing per protocol
• Prior ECP \> 2 months in duration within 3 months of registration
• Patients with ECP treatment prior to registration will be eligible regardless of date ECP was received (as long as it was not \> 2 months in duration within the 3 months immediately prior to registration), as long as they have measurable disease at the time of enrollment
• Use of topical steroids within 14 days of day 1 of initial therapy is not allowed, with the following exception:
• Topical steroids or systemic low dose steroids (=\< 10 mg/day prednisone) are allowed in subjects with erythroderma who have been on corticosteroids for a prolonged period of time and where discontinuation may lead to rebound flare in disease. The concomitant steroid medication is allowed as long as the type of steroid, route of administration, and steroid dose remain the same as what the subject had been receiving for a prolonged period of time
• Severe or uncontrolled autoimmune condition
• Active, life threatening malignancy (except for CTCL, definitively treated basal or squamous cell carcinoma of the skin, and carcinoma in-situ of the cervix, or other localized malignancies treated with curative intent with surgery or radiation alone) within the past 12 months
• Serious intercurrent illness
• Known significant cardiac disease requiring ongoing treatment, including congestive heart failure (CHF), severe coronary artery disease (CAD), cardiomyopathy, uncontrolled cardiac arrhythmia, unstable angina pectoris, or myocardial infarction (MI) (within 6 months of study enrollment)

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous; Sezary Syndrome

Interventions

Photopheresis; mogamulizumab; Immunoglobulin G; Disulfides

Condition Hierarchy (Ancestors)

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)

PUVA Therapy; Ultraviolet Therapy; Phototherapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Study Officials

• Pamela B Allen

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 9, 2020
• First Posted: December 19, 2020
• Study Start: April 21, 2021
• Primary Completion: October 11, 2023
• Study Completion: October 11, 2023
• Last Updated: August 13, 2024

Record last verified: 2024-08

Locations

US (1)