Innocuité, pharmacodynamique et efficacité du MT-3724 dans le traitement des patients atteints d’un LBDGC récidivant ou réfractaire

Titre officiel

Innocuité, pharmacodynamique et efficacité du MT-3724 dans le traitement des patients atteints d’un LBDGC récidivant ou réfractaire

Sommaire:

Cette étude de phase I à doses multiples croissantes vise à inscrire des sujets atteints d’un lymphome non hodgkinien à cellules B progressif présentant des lésions mesurables [> 1,5 cm] (y compris le petit lymphome lymphocytaire [PLL]) OU atteints d’un PLL récidivant/réfractaire à cellules B ayant reçu un traitement standard par un schéma de première intention renfermant au moins un anticorps anti-CD20 (p. ex. le rituximab ou l’ofatumumab), celui-ci ayant entraîné une réponse initiale suivie d’une récidive/récurrence, et qui ne sont pas admissibles à aucun autre traitement biologique, chimiothérapie et/ou greffe de cellules souches autologues approuvé et/ou qui ont refusé tout autre traitement approuvé et/ou qui sont peu susceptibles d’obtenir des bienfaits cliniques de tout traitement de priorité plus élevée selon l’évaluation de l’investigateur.

Description de l'essai

Primary Outcome:

• Tolerability as measured by number of subjects with dose limiting toxicities
• Safety as measured by number of subjects with Adverse Events using CTCAE
• Efficacy of MT-3724 (Part 3)

Secondary Outcome:

• PK Assessment of MT-3724 by Cmax
• PK Assessment of MT-3724 by tmax
• PK Assessment of MT-3724 by AUC0-4
• PK Assessment of MT-3724 by AUC0-inf
• PK Assessment of MT-3724 by AUClast
• PK Assessment of MT-3724 by t1/2
• PK Assessment of MT-3724 by Vz
• PK Assessment of MT-3724 by CL
• PD as measured by clinical symptoms, immunogenicity
• Efficacy of MT-3724 (Part 3) as based on ORR
• Efficacy of MT-3724 (Part 3) as based on DOR
• Efficacy of MT-3724 (Part 3) as based on DCR
• Efficacy of MT-3724 (Part 3)as based on PFS
• Efficacy of MT-3724 (Part 3) as based on OS
• PD as measured by B-cell count and immunophenotype in peripheral blood as determined by flow cytometry measured against MT-3724 serum concentrations at pre-specified time points
• Immunogenicity as measured by MT-3724 anti-drug antibody (ADA) titer
• Quality of life as assessed through Euro-QoL Questionnaire (Part 3)
• Safety as measured by number of subjects with Adverse Events using CTCAE

This is a three-part Phase 2 study Part 1: (MT-3724 Dose Escalation) Define the maximum tolerated dose (MTD) of MT-3724 [Completed] Part 2: (MTD Expansion Cohort) Confirm the safety and tolerability of the MTD of MT-3724 in the MTD Expansion Cohort. Part 3: (Phase 2 MTD Expansion Cohort) Determine the efficacy of MT-3724 as monotherapy in subjects with relapsed or refractory DLBCL based on the overall response rate (ORR) by the revised Lugano Classification for Lymphoma adjusted according to LYRIC. It is anticipated that up to 100 patients will be enrolled in Part 3. Treatment will continue for up to six 21 days cycles. If the subject exhibits SD, CR or PR after the end of Cycle 6 and the investigator determines that the benefit-risk ratio is favourable, then the treatment with MT-3724 may be continued after discussion with the sponsor.

Voir cet essai sur ClinicalTrials.gov