E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed/Refractory Cutaneous T-Cell Lymphoma (CTCL) - Mycosis fungoides and Sezary syndrome |
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E.1.1.1 | Medical condition in easily understood language |
A type of cancer affecting the skin and/or other parts of the body |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 22.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028510 |
E.1.2 | Term | Mycosis fungoides/Sezary syndrome recurrent |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
• 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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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). |
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E.4 | Principal 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 < 0.1 ng/mL, treated thyroid cancer, or cervical carcinoma in situ or ductal/lobular carcinoma in situ of the breast within the past 2 years may enroll as long as there is no current evidence of disease. 3) Clinical evidence of central nervous system (CNS) metastasis. 4) Psychiatric illness, disability, or social situation that would compromise the participant’s safety or ability to provide consent, or limit compliance with study requirements. 5) Significant uncontrolled intercurrent illness including, but not limited to: a) uncontrolled infection requiring antibiotics; b) clinically significant cardiac disease (class III or IV of the NYHA classification); c) unstable angina pectoris; d) angioplasty, stenting, or myocardial infarction within 6 months; e) uncontrolled hypertension (systolic blood pressure [BP] > 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) Participants on a stable dose of medium or low potency topical corticosteroids for at least 4 weeks prior to the Pre-treatment Visit may continue use at the same dose, although the Investigator should attempt to taper the use to the lowest dosage tolerable while on study. Initiation of treatment with topical corticosteroids while on study is not permitted except to treat an acute rash. 15) History of allogeneic transplant. 16) Autologous hematopoietic stem cell transplant within 90 days of the Pre-treatment Visit. 17) Participants will be excluded if on any immunomodulatory drug for concomitant or intercurrent conditions other than T-cell lymphoma or who have received any of these agents within 4 weeks of treatment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Percentage of participants experiencing treatment-emergent adverse events. • Changes in laboratory analyses, physical examinations, vital signs, and ECGs. |
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E.5.1.1 | 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) |
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E.5.2 | 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.
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E.5.2.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United States |
France |
Italy |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of trial is 2 years from the last participant’s first dose or when all participants discontinue treatment, whichever occurs first. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |