Clinical Trials/NCT06495723

NCT06495723

Recruiting

Phase 1

Phase I/II, Open-label, Multi-center Study to Evaluate the Safety and Efficacy of Glyco-humanized Polyclonal Antibody Directed Against Tumoral T Cells, in Patients With Relapsed/Refractory Peripheral T Cells Lymphoma (PTCL)

Xenothera SAS8 sites in 2 countries54 target enrollmentJuly 9, 2024

ConditionsPeripheral T Cells Lymphoma (PTCL)

InterventionsLIS1

Overview

Phase: Phase 1
Intervention: LIS1
Conditions: Peripheral T Cells Lymphoma (PTCL)
Sponsor: Xenothera SAS
Enrollment: 54
Locations: 8
Primary Endpoint: Dose Escalation part: Dose Limiting Toxicities (DLTs)
Status: Recruiting
Last Updated: 9 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

July 9, 2024

End Date

July 31, 2027

Last Updated

9 months ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Xenothera SAS

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Provide signed, written informed consent.
•Is male or female, age ≥18 years old (at the time consent is obtained)
•For Part 1: Has a histological diagnosis of the following relapsed or refractory PTCL based on WHO 2022 classification of lymphoid neoplasms
•Intestinal T-cell and NK cell lymphoid proliferations and lymphomas (without NK cell neoplasms)
•Hepatosplenic T-cell lymphoma
•Anaplastic large cell lymphoma
•Nodal TFH cell lymphoma
•Other peripheral t-cell lymphomas For Part 2: The type of PTCL will be defined based on SC review after completion of Part 1 and will be documented in the protocol amendment
•Had previously received 1 or more appropriate systemic therapies, including an alkylating agent and/or anthracycline, for treatment of the current disease (radiation therapy alone would not be acceptable as previous therapy). Participants with ALCL must have received prior brentuximab vedotin or be unable to receive it due to allergy or intolerance.
•Experienced disease progression during or after completion of most recent therapy or refractory disease.

Exclusion Criteria

•Is diagnosed with a bulky disease (≥10 cm).
•Has known history or presence of central nervous system involvement by leukemia or lymphoma.
•Has Mature T-cell and NK-cell leukemias (WHO 2022 criteria)
•Has T-lymphoblastic leukemia/lymphoma (WHO 2022 criteria)
•Has tumor-like lesions with T-cell predominance (WHO 2022 criteria)
•Has Primary cutaneous T-cell lymphomas (WHO 2022 criteria)
•Has any other active cancers, or history of treatment for invasive cancer ≤3 years.
•Note: Participants with stage I cancer who have received definitive local treatment at least 3 years previously and are considered unlikely to recur are eligible. All participants with previously treated in situ carcinoma (i.e., non-invasive) are eligible.
•Received any of the following treatments prior to the first dose of study medication:
•Systemic chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks (or 5 half-lives, whichever is shorter) before Cycle 1 Day

Arms & Interventions

Dose Escalation part: dose 2 mg/kg

Dose Escalation part: Dose level of LIS1: 2 mg/kg.

Intervention: LIS1

Dose Escalation part: dose 4 mg/kg

Dose Escalation part: Dose level of LIS1: 4 mg/kg.

Intervention: LIS1

Dose Escalation part: dose 6 mg/kg

Dose Escalation part: Dose level of LIS1: 6 mg/kg.

Intervention: LIS1

Expansion part

Expansion part: Participants will receive LIS1 at the RP2D determined in Part 1 of the study.

Intervention: LIS1

Outcomes

Primary Outcomes

Dose Escalation part: Dose Limiting Toxicities (DLTs)

Time Frame: At the end of Cycle 1 (28 days)

Incidence of DLTs in the first cycle

Dose Escalation part: treatment emergent adverse events (TEAEs)

Time Frame: After the first dose of study intervention through 60 days following the last dose of study intervention.

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.

Expansion part: Anti-tumors efficacy

Time Frame: Within 3 months after LIS1 initiation

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.

Secondary Outcomes

Expansion part: Proportion of Progressive Disease (PD) as best overall response(Within 3 months and 6 months after LIS1 initiation)
Expansion part: Duration of response (DoR)(Within 3 months and 6 months after LIS1 initiation)
Pharmacokinetics (PK) of LIS: Vd(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: Cmax(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(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(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(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: Proportion of Complete Response (CR) as best overall response(Within 3 months and 6 months after LIS1 initiation)
Expansion part: Proportion of Partial Response (PR) as best overall response(Within 3 months and 6 months after LIS1 initiation)
Expansion part: Proportion of Stable Disease (SD) as best overall response(Within 3 months and 6 months after LIS1 initiation)
Expansion part: treatment emergent adverse events (TEAEs)(After the first dose of study intervention through 60 days following the last dose of study intervention.)
Expansion part: Time to response (TTR)(Within 3 months and 6 months after LIS1 initiation)
Expansion part: Progression-free survival (PFS)(Within 3 months and 6 months after LIS1 initiation)
Expansion part: Overall survival (OS)(Within 3 months and 6 months after LIS1 initiation)
Expansion part: Proportion of patients "bridged to transplantation"(Through study completion, an average of 1 year.)
Pharmacokinetics (PK) of LIS: Ctrough(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(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(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(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.)