Lymphoma, T-Cell, Cutaneous, Mycosis Fungoides, Sezary Syndrome
Conditions
Keywords
Cutaneous T-Cell Lymphoma (CTLC), Maintenance, resminostat, 4SC, HDAC, Mycosis Fungoides, Sézary Syndrome
Brief summary
The purpose of this study is to determine whether resminostat will be able to delay or prevent worsening of disease in patients with advanced stage mycosis fungoides or Sézary Syndrome that have recently achieved disease control with previous systemic therapy.
Interventions
DRUGresminostat
DRUGPlacebo
Sponsors
4SC AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Patients with histologically confirmed MF (Stage IIB-IVB) or SS in an ongoing complete response (CR), partial response (PR) or stable disease (SD) after at least one prior systemic therapy according to local standards (including but not limited to α-interferon, bexarotene, total skin electron beam irradiation, chemotherapy) \[the most recent systemic therapy must have been completed as planned or stopped due to unacceptable toxicity 2-12 weeks prior to randomisation\] * Eastern Cooperative Oncology Group (ECOG) status score 0-2 * Adequate haematological, hepatic and renal function Main
Exclusion criteria
* Patients with progressive disease (PD) * Baseline corrected QT (QTc) interval \> 500 milliseconds * Concurrent use of any other specific anti-tumour therapy including psoralen photo chemotherapy (PUVA), chemotherapy, immunotherapy, hormonal therapy, radiation therapy, or experimental medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS (Progression-free survival) | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to approximately 32 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| TTSW (Time to symptom worsening): pruritus | From date of randomisation to first date that criteria for symptom (pruritus) worsening have been met, up to approximately 32 months. Symptom worsening is defined as an increase of a minimum of 3 points on the visual analogue itching scale | To determine if maintenance treatment with resminostat increases time to symptom (pruritus) worsening (TTSW) compared to placebo. |
Other
| Measure | Time frame | Description |
|---|---|---|
| TTNT (Time to next treatment) | From date of randomisation to first date that new treatment is received, up to approximately 44 months. | Compare time to next treatment (TTNT) in patients when treated with resminostat vs placebo |
| PFS2, PFS3 (Progression-free survival 2, 3) | From date of start of subsequent treatment to date of progression or death due to any cause in the absence of documented PD whilst receiving second and third line therapy, respectively, up to approximately 44 months | Assess the effect of maintenance treatment with resminostat by means of PFS of subsequent treatments (PFS2, PFS3) |
| ORR (Overall response rate) | Percent of patients within each treatment Arm that achieve confirmed CR or PR relative to the number of patients belonging to the analysis population of interest, up to approximately 32 months. | Compare overall response rate (ORR, including CR, PR) in patients when treated with resminostat vs placebo |
| DOR (Duration of response) | From date confirmed CR or PR (whichever is first) until the criteria for PD have been met, up to approximately 32 months. | Compare duration of response (DOR) in patients when treated with resminostat vs placebo |
| OS (Overall survival) | From the day of randomisation to death from any cause, up to approximately 44 months. | Compare overall survival (OS) in patients when treated with resminostat vs placebo |
| Incidence of treatment-related AEs and SAEs (Safety and tolerability) | Weekly for 3 cycles, then bi-weekly during treatment phase, up to approximately 9 months | Assess the safety and tolerability of resminostat |
| HrQoL (Health related quality of life) | Every 28 days, up to approximately 32 months | Compare changes in health related quality of life (HrQoL) parameters in patients when treated with resminostat vs placebo |
| Maximum Plasma Concentration [Cmax] | At Cycle 3, Day 1 at 0.75h, 2h and 4 h after intake of trial medication / at Cycle 3, Day 5 to be done pre-dose and at 2h and 7h after intake of trial medication | Assess the maximum plasma concentration \[Cmax\] of resminostat and metabolites |
| Area Under the Curve [AUC] | At Cycle 3, Day 1 at 0.75h, 2h and 4 h after intake of trial medication / at Cycle 3, Day 5 to be done pre-dose and at 2h and 7h after intake of trial medication | Assess the Area Under the Curve \[AUC\] of resminostat and metabolites |
| TTP (Time to progression) | From date of randomization until the date of first documented progression, up to approximately 32 months | Compare time to progression (TTP) in patients when treated with resminostat vs placebo |
Countries
Austria, Belgium, France, Germany, Greece, Italy, Japan, Netherlands, Poland, Spain, Switzerland, United Kingdom
Outcome results
None listed