This is a 2-part study consisting of a Part 1, dose escalation and dose-finding component to establish the Maximal Tolerated Dose (MTD), or Recommended Part 2 Dose (RP2D) of LIS1 as a single agent; followed by a Part 2, to investigate anti-tumors efficacy of LIS1 in selected subtypes of Peripheral TCell Lymphoma (PTCL) and to further evaluate its safety and tolerability at RP2D.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
54
The study intervention (LIS1) is a glyco-humanized polyclonal antibody drug which is formulated for IV administration.
CHU de Caen
Caen, France
RECRUITINGCHU de Clermont-Ferrand
Clermont-Ferrand, France
RECRUITINGCHU Henri-Mondor
Créteil, France
Dose Escalation part: Dose Limiting Toxicities (DLTs)
Incidence of DLTs in the first cycle
Time frame: At the end of Cycle 1 (28 days)
Dose Escalation part: treatment emergent adverse events (TEAEs)
The severity of averse events (AEs) will be graded according to the NCI CTCAE, v5.0. Treatment-emergent adverse events are defined as any AE with onset or worsening of a pre existing condition after the first dose of study intervention through 60 days following the last dose of study intervention.
Time frame: After the first dose of study intervention through 60 days following the last dose of study intervention.
Expansion part: Anti-tumors efficacy
Objective response rate (ORR): defined as the proportion of participants with CR or PR assessed by Investigators according to Lugano criteria with the LYRIC modification for immunomodulatory drug.
Time frame: Within 3 months after LIS1 initiation
Pharmacokinetics (PK) of LIS: Cmax
LIS1 peak plasma concentration (Cmax) in plasma
Time frame: At Cycle1Day 1 Predose and 5 minutes; 1; 2; 4; 8; 24 hours after the end of infusion. At Day1 and Day15 of Cycle2 to 6 (each cycle is 28 days): Predose and 5 minutes after the end of infusion. At Day 30 and Day60 after the last dose of LIS1.
Pharmacokinetics (PK) of LIS: Tmax
Time to peak drug concentration in plasma (Tmax)
Time frame: At Cycle1Day 1 Predose and 5 minutes; 1; 2; 4; 8; 24 hours after the end of infusion. At Day1 and Day15 of Cycle2 to 6 (each cycle is 28 days): Predose and 5 minutes after the end of infusion. At Day 30 and Day60 after the last dose of LIS1.
Pharmacokinetics (PK) of LIS: AUC
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CHU de Bordeaux - GH Sud - Hôpital Haut-Lévêque
Pessac, France
RECRUITINGCHU de Lyon - Hôpital Lyon Sud
Pierre-Bénite, France
RECRUITINGSC Ematologia Istituto Nazionale dei TumoriIRCCS Fondazione "G. Pascale"
Naples, Campania, Italy
RECRUITINGIRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola
Bologna, Emilia-Romagna, Italy
RECRUITINGFondazione IRCCS Istituto Nazionale dei Tumori
Milan, Lombardy, Italy
RECRUITINGAUC24hours; AUC0-14days; AUC15-28days and AUC0-28days will be assessed
Time frame: At Cycle1Day 1 Predose and 5 minutes; 1; 2; 4; 8; 24 hours after the end of infusion. At Day1 and Day15 of Cycle2 to 6 (each cycle is 28 days): Predose and 5 minutes after the end of infusion. At Day 30 and Day60 after the last dose of LIS1.
Pharmacokinetics (PK) of LIS: Ctrough
Trough concentration (Ctrough) is the concentration reached by LIS1 immediately before the next dose is administered
Time frame: At Cycle1Day 1 Predose and 5 minutes; 1; 2; 4; 8; 24 hours after the end of infusion. At Day1 and Day15 of Cycle2 to 6 (each cycle is 28 days): Predose and 5 minutes after the end of infusion. At Day 30 and Day60 after the last dose of LIS1.
Pharmacokinetics (PK) of LIS: Cmin
Cmin for the minimum blood plasma concentration reached by LIS1 during the time interval between administration of two doses
Time frame: At Cycle1Day 1 Predose and 5 minutes; 1; 2; 4; 8; 24 hours after the end of infusion. At Day1 and Day15 of Cycle2 to 6 (each cycle is 28 days): Predose and 5 minutes after the end of infusion. At Day 30 and Day60 after the last dose of LIS1.
Pharmacokinetics (PK) of LIS: T1/2
Half-life (T1/2) refers to the time required for plasma concentration of LIS1 to decrease
Time frame: At Cycle1Day 1 Predose and 5 minutes; 1; 2; 4; 8; 24 hours after the end of infusion. At Day1 and Day15 of Cycle2 to 6 (each cycle is 28 days): Predose and 5 minutes after the end of infusion. At Day 30 and Day60 after the last dose of LIS1.
Pharmacokinetics (PK) of LIS: CL
Clearance (CL) is the volume of blood or plasma cleared of LIS1 from the body per unit of time
Time frame: At Cycle1Day 1 Predose and 5 minutes; 1; 2; 4; 8; 24 hours after the end of infusion. At Day1 and Day15 of Cycle2 to 6 (each cycle is 28 days): Predose and 5 minutes after the end of infusion. At Day 30 and Day60 after the last dose of LIS1.
Pharmacokinetics (PK) of LIS: Vd
Volume of distribution (Vd) is defined as the total amount of LIS1 in the body divided by its concentration in plasma
Time frame: At Cycle1Day 1 Predose and 5 minutes; 1; 2; 4; 8; 24 hours after the end of infusion. At Day1 and Day15 of Cycle2 to 6 (each cycle is 28 days): Predose and 5 minutes after the end of infusion. At Day 30 and Day60 after the last dose of LIS1.
Host immunogenicity to LIS1
Number of participants who develop detectable anti-drug antibodies
Time frame: Before and after (up to 5 min after the infusion) LIS1 infusion at Cycle1Day 1, Cycle1Day8, Cycle1Day15, and Cycle1Day22, then before infusion at Day1 and Day15 of Cycle2 to Cycle6 (each cycle is 28 days), and at Day30 and Day60 after last dose of LIS1
Expansion part: treatment emergent adverse events (TEAEs)
The severity of averse events (AEs) will be graded according to the NCI CTCAE, v5.0. Treatment-emergent adverse events are defined as any AE with onset or worsening of a pre existing condition after the first dose of study intervention through 60 days following the last dose of study intervention.
Time frame: After the first dose of study intervention through 60 days following the last dose of study intervention.
Expansion part: Proportion of Complete Response (CR) as best overall response
Proportion of Complete Response as best overall response
Time frame: Within 3 months and 6 months after LIS1 initiation
Expansion part: Proportion of Partial Response (PR) as best overall response
Proportion of PR as best overall response
Time frame: Within 3 months and 6 months after LIS1 initiation
Expansion part: Proportion of Stable Disease (SD) as best overall response
Proportion of SD as best overall response
Time frame: Within 3 months and 6 months after LIS1 initiation
Expansion part: Proportion of Progressive Disease (PD) as best overall response
Proportion of PD as best overall response
Time frame: Within 3 months and 6 months after LIS1 initiation
Expansion part: Duration of response (DoR)
DoR: defined as the time interval between the first confirmed objective response (CR or PR) and the first occurrence of objective progression (PD) or death from any cause.
Time frame: Within 3 months and 6 months after LIS1 initiation
Expansion part: Time to response (TTR)
TTR: defined as the time from the date of LIS1 initiation to first confirmed objective response (CR or PR)
Time frame: Within 3 months and 6 months after LIS1 initiation
Expansion part: Progression-free survival (PFS)
PFS: defined as the time from the date of LIS1 initiation to the date of first documented progression or death
Time frame: Within 3 months and 6 months after LIS1 initiation
Expansion part: Overall survival (OS)
OS: defined as the time interval between the date of LIS1 initiation and the date of death due to any cause
Time frame: Within 3 months and 6 months after LIS1 initiation
Expansion part: Proportion of patients "bridged to transplantation"
Proportion of patients with a stem cell transplantation after LIS1 treatment
Time frame: Through study completion, an average of 1 year.