Relapsed/Refractory Cutaneous T-Cell Lymphoma (CTCL) - Mycosis fungoides and Sezary syndrome MedDRA version: 22.0 Level: LLT Classification code 10028510 Term: Mycosis fungoides/Sezary syndrome recurrent System Organ Class: 100000004864
Conditions
Interventions
Trade Name: POTELIGEO
Product Name: Mogamulizumab
Product Code: KW-0761
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Mogamulizumab
CAS Number: 1159266-37-1
Current
Sponsors
Kyowa Kirin Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Voluntarily signed and dated institutional review board (IRB)/ ethics committee (EC) approved informed consent obtained prior to performing any study-related procedur in accordance with regulatory and institutional guidelines. 2) Male and female participants equal to or more than 18 years of age at the Pre-treatment Visit. 3) Histologically confirmed diagnosis of MF or SS. - Stage IB, II-A, II-B, III, or IV (Olsen, 2011); 4) Participants who have failed at least one prior course of systemic therapy (e.g., interferon, bexarotene, photopheresis, anti-neoplastic chemotherapy). Psoralen plus UVA is not considered a systemic therapy. 5) ECOG performance status score of = 1. 6) The participant has resolution of all clinically significant toxic effects of prior cancer therapy to Grade = 1 according to NCI-CTCAE (v.5.0), excluding the specifications required in 7, 8, and 9 below. 7) Adequate hematological function, defined as: a) Absolute neutrophil count (ANC) = 1000 cells/uL (= 1000/mm3) and b) Platelets =75,000 cells/uL (=75,000/mm3); 8) Adequate hepatic function, defined as: a) Bilirubin = 1.5 times the specific institutional upper limit of normal (ULN), except for participants with Gilbert’s syndrome. b) Aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/serum glutamic-pyruvic transaminase (ALT/SGPT) each = 2.5 × ULN or = 5.0 × ULN in the presence of known hepatic involvement by CTCL. 9) Adequate renal function, defined as calculated creatinine clearance = 30 mL/min using the Cockcroft-Gault formula. 10) Participants previously treated with anti-CD4 antibody or alemtuzumab are eligible, provided their CD4+ cell counts are = 200/mm3. 11) Participants with MF and a known history of non-complicated staphylococcus colonization/infection are eligible, provided they continue to receive stable doses of prophylactic antibiotics. 12) Women of childbearing potential must have a negative pregnancy test within 7 days prior to receiving study medication. 13) Women of childbearing potential must agree to use effective contraception, defined as oral contraceptives, double barrier method (condom plus spermicide or diaphragm plus spermicide) or practice true abstinence from sexual intercourse (periodic abstinence, e.g., calendar, ovulation, symptothermal, post-ovulation methods, and withdrawal, are not acceptable methods of contraception) during the study and for 6 months after the last dose. • Women of childbearing potential includes any female who has experienced menarche and who has not undergone successful surgical sterilization or is not postmenopausal (defined as amenorrhea = 12 consecutive months without an alternative medical cause). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 17 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: 1) Current evidence of large cell transformation (LCT). Participants with clinical features suggestive of LCT must have a biopsy performed within 4 months prior to Cycle 1 Day 1 to rule out transformed disease. Participants with a history of LCT but without current aggressive disease and no current evidence of LCT on pathology in skin or lymph nodes would be eligible. 2) Diagnosed with another malignancy in the past 2 years. However, participants with non-melanoma skin cancers, melanoma in situ, localized cancer of the prostate with current prostate-specific antigen of 160 mmHg or diastolic BP > 100 mmHg, found on 2 consecutive measurements separated by a 1-week period) despite the use of 2 anti-hypertensive medications; f) clinically significant cardiac arrhythmia; or g) uncontrolled diabetes. 6) Active human immunodeficiency virus (HIV), human T-cell lymphotropic virus, type 1, hepatitis B, or hepatitis C disease. 7) Active herpes simplex or herpes zoster. Participants on prophylaxis for herpes may enter the study and should continue to take the prescribed medication for the duration of the study if they started taking medication at least 30 days prior to the Pre-treatment Visit, have no signs of active infection, and their last active infection was more than 6 months ago. 8) Experienced allergic reactions to monoclonal antibodies or other therapeutic proteins. 9) Known active autoimmune disease (i.e., Graves’ disease; systemic lupus erythematosus; rheumatoid arthritis; Crohn’s disease; psoriasis). 10) Is pregnant (confirmed by beta human chorionic gonadotropin) or lactating. 11) Prior treatment with mogamulizumab. 12) Have had any therapy directed against the participant’s underlying cancer or any investigational medications within 4 weeks of randomization (skin directed treatments, including topicals and radiation within 2 weeks of randomization). However, participants with rapidly progressive malignant disease may be enrolled prior to this period after discussion with and approval from the Medical Monitor. 13) Participants on a stable dose of a low dose systemic corticosteroid (= 20 mg prednisone equivalent) for at least 4 weeks prior to the Pre-treatment Visit may continue use, although the Investigator should attempt to taper the use to the lowest dosage tolerable while on study. Initiation of treatment with systemic corticosteroids or increase in dose while on study is not permitted except to treat an infusion reaction. Participants may receive intra-articular corticosteroid injections, intraocular corticosteroid drops, inhalation or nasal corticosteroids, and replacement doses of systemic corticosteroids as needed. 14)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of mogamulizumab given every 4 weeks in participants with relapsed/refractory mycoses fungoides (MF) or Sézary syndrome (SS) subtypes of CTCL.;Secondary Objective: • To characterize the pharmacokinetics (PK) of mogamulizumab following 2 mg/kg Q4W IV administration. • To evaluate the anti-tumor activity of mogamulizumab in participants with relapsed/refractory MF or SS (overall response rate [ORR] and duration of response [DOR]) as assessed by Investigators. • To characterize the immunogenicity of mogamulizumab following 2 mg/kg Q4W IV administration. • To evaluate the pharmacodynamic (PDyn) profile.;Primary end point(s): • Percentage of participants experiencing treatment-emergent adverse events. • Changes in laboratory analyses, physical examinations, vital signs, and ECGs.;Timepoint(s) of evaluation of this end point: TEAEs will be collected throughout study; other safety assessments will be carried out at clinic visits (refer to schedule of activities) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Serum concentrations of mogamulizumab and other PK parameters. • ORR will be assessed as described by Olsen (2011). • DOR will be calculated from first response to progression or death. • Detection of anti-drug antibodies (ADAs) to mogamulizumab and incidence of ADAs. • Fresh tissue samples will be assessed for changes in CCR4, CD4, and CD8 expression. • Blood samples will be assessed for circulating malignant T-cells. ;Timepoint(s) of evaluation of this end point: Please refer to the Schedule of Activities (SoAs) in the protocol PK at Cycle 1 Days 1, 8, 15 & 22; ORR & DOR: Cycle 1, Day 28 and every 8 weeks thereafter; ADAs: Day 1 of Cycles 1, 2, 3, 5, 9, 13, 19 and 25; CCR4, CD4 & CD8 expression: Cycle 1 Day 28; Circulating malignant T-cells: every 4 weeks | — |
Countries
France, Italy, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Kyowa Kirin Inc.
Outcome results
None listed