E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced stage (Stage IIB-IVB) mycosis fungoides (MF) or Sézary Syndrome (SS) that have achieved disease control with systemic therapy |
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E.1.1.1 | Medical condition in easily understood language |
Specific type of lymphoma affecting the skin (Mycosis fungoides or Sézary Syndrome) which has treated recently with systemic therapy, responded to this treatment and has been stabilized |
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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 | 10028508 |
E.1.2 | Term | Mycosis fungoides/Sezary syndrome |
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 |
The primary objective is to determine if maintenance treatment with resminostat increases progression free survival (PFS) compared to placebo in patients with advanced stage (Stage IIB-IVB) MF or SS that have achieved disease control (complete response [CR], partial response [PR] or stable disease [SD]) with previous systemic therapy.
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E.2.2 | Secondary objectives of the trial |
Key Secondary Objective
•To determine if maintenance treatment with resminostat increases time to symptom (pruritus) worsening (TTSW) compared to placebo.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Patients with histologically confirmed MF (Stage IIB-IVB) or SS in an ongoing CR, PR or SD after at least one prior systemic therapy according to local standards (including but not limited to α-interferon, bexarotene, extracorporeal photopheresis, chemotherapy) or total skin electron beam irradiation
o the most recent systemic therapy must have been completed as planned or stopped due to unacceptable toxicity 2-12 weeks prior to randomisation, i.e. patients should not be withdrawn from a treatment from which they derive benefit
2.Male or female ≥ 18 years
3.Written informed consent obtained prior to any trial specific procedure
4.Eastern Cooperative Oncology Group (ECOG) status score 0-2
5.Adequate haematological, hepatic and renal function, as demonstrated by:
a)haemoglobin ≥ 9.0 g/dl (International System [SI] of Units: 5.6 mmol/L)
b)absolute neutrophil count ≥ 1,000/mm3
c)platelets ≥ 75 × 109/L
d)alanine aminotransferase and aspartate amino-transferase ≤ 2 times upper limit of normal
e)total bilirubin ≤ 2 mg/dL (SI units: 34.2 µmol/L) (unless known Gilbert syndrome)
f)serum creatinine ≤ 1.5 mg/dL (SI units: 132 µmol/L)
g)prothrombin time International Normalised Ratio ≤ 2.3
6.Women of childbearing potential (not post-menopausal for 1 year and not surgically sterile) and males with partners of childbearing potential must be sexually abstinent (i.e. refraining from heterosexual intercourse) or must use a highly effective contraception (at least one of the following: combined (oral, intravaginal or transdermal) or progestogen-only (oral, injectable or implantable) hormonal contraceptives, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomy of the partner from the time of screening to 30 days (female patients) or 3 months (male patients) after the last dose of trial treatment
7.Adequate recovery from precedent non-haematological toxicities, excluding alopecia, to ≤ National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 1
8.Able to comply with all the requirements of the protocol
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E.4 | Principal exclusion criteria |
1.Patients with PD
2.Known central nervous system involvement
3.History and current cardiovascular complications, including unstable angina pectoris, uncontrolled hypertension, congestive heart failure (New York Heart Association [NYHA] Class III or IV) related to primary cardiac disease, a condition requiring anti arrhythmic therapy, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to randomisation
4.Baseline corrected QT (QTc) interval > 500 milliseconds [NOTE: QTcF is relevant]
5.History of additional risk factors for Torsade de Pointes (e.g., heart failure, hypokalaemia, family history of Long QT Syndrome)
6.Use of concomitant medications that are known to prolong the QT/QTc interval
7.Concurrent use of any other specific anti tumour therapy including psoralen photo chemotherapy (PUVA), chemotherapy, immunotherapy, hormonal therapy, radiation therapy, or experimental medications
8.Previous or concurrent cancer that is distinct in primary site or histology from CTCL, except curatively treated squamous-cell carcinoma of the skin stage 0-1 and curatively treated melanoma stage 0-1A with a low risk of recurrence/metastasis as per assessment of the investigator, cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumours (Ta, Tis and T1); any cancer curatively treated > 3 years prior to randomisation will be allowed
9.Current evidence of any uncontrolled clinically significant internal, psychiatric or neurologic disease
10.Altered mental status precluding understanding of the informed consent process and/or completion of the necessary trial procedures
11.Pregnant or breast feeding women
12.History of allergic reactions attributed to compounds of similar chemical or biological composition to the trial drugs
13.Active alcohol and/or drug abuse
14.Any other acute or chronic condition that, in the investigator’s opinion, would limit the patient’s ability to complete or participate in this trial
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival (PFS) is defined as the time from date of randomisation to first date that criteria for PD have been met according to the global response score or death due to any cause in the absence of documented PD. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PFS (progression free survival) is defined as the time from date of
randomisation to first date that criteria for progressive disease (PD)
have been met according to the global response score or death due to
any cause in the absence of documented PD. |
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E.5.2 | Secondary end point(s) |
Key Secondary Endpoint
•TTSW (pruritus)
Secondary Endpoints
•TTP
•TTNT
•PFS2
•PFS3
•ORR (CR, PR)
•DOR
•OS
•HrQoL
oVAS (itching)
oFACT-G
oSkindex-29
•PK analysis (peripheral blood)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
TTSW (pruritus), the key secondary endpoint, is defined as the time from date of randomisation to first date that criteria for symptom (pruritus) worsening have been met. |
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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 | Yes |
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 | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
open label phase to follow the blinded phase, see protocol for details |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 48 |
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 |
Japan |
Austria |
Belgium |
France |
Germany |
Italy |
Netherlands |
Poland |
Spain |
Switzerland |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |