Tinostamustine Conditioning and Autologous Stem Cell — TITANIUM1  

Multiple Myeloma in Relapse Clinical Trial

Official title: Phase 1/2 Open-label Trial of Tinostamustine Conditioning and Autologous Stem Cell Transplantation for Salvage Treatment in Relapsed / Refractory Multiple Myeloma (TITANIUM 1)

Status Terminated

Clinical Trial Summary

Phase 1

The primary objectives of Phase 1 of this study are to:

• Establish the safety, toxicity, and maximum tolerated dose (MTD) of the tinostamustine conditioning regimen.

• Identify the recommended Phase 2 dose (RP2D) of tinostamustine for use in the Phase 2 portion of the study.

The secondary objective of Phase 1 of this study is to:

• Investigate the pharmacokinetics (PK) of tinostamustine.

Clinical Trial Description

Study Design (Methodology):

This is a 2-part, international, multi-center, open-label study of salvage treatment with tinostamustine conditioning followed by ASCT in participants with relapsed/ refractory multiple myeloma (MM). (ASCT is defined as salvage if the participant had already received a prior ASCT and undergoes a second ASCT after evidence of progressive disease [PD].) Phase 1 of the study employs a standard 3+3 dose escalation design with the objective of defining the dose limiting toxicities (DLTs) of the tinostamustine conditioning regimen and defining the MTD and RP2D for use in the Phase 2 portion of the study.

The Safety Review Committee can make a decision to stop dose escalation or explore intermediary doses at any time. The total dose of tinostamustine will be administered on Day -1. Phase 2 of the study employs a 2-step sequential design (Simon, 1989). In Stage 1 of Phase 2, up to 31 participants initially will be enrolled. If lesser than or equal to (<=) 25 participants of these initial 31 participants experience a response, then no additional participants will be enrolled. However, if greater than (>) 25 participants in Stage 1 of Phase 2 experience a response, then enrollment in this cohort will continue, with up to 71 participants enrolled. In Phase 2 of the study, all participants will receive tinostamustine at the RP2D administered in Phase 1 according to the same schedule. After provision of written informed consent, participants will be screened for study eligibility within 28 days before Day 1 (the day of ASCT). Participants who have a minimum of 2×106 CD34+ cells/kg cryopreserved and are otherwise determined to be eligible, based on screening assessments, will be enrolled and receive the tinostamustine conditioning regimen. The tinostamustine dose will be administered 24 hours pre-ASCT (i.e., Day -1). On Day 1, ASCs will be administered intravenously (IV) according to standard institutional practice. Participants will receive supportive measures (including growth factor support post-ASCT, antimicrobial prophylaxis, red blood cell and platelet transfusion, and treatment for neutropenic fever) according to standard institutional practice. ;

Related Conditions & MeSH terms

• Multiple Myeloma
• Multiple Myeloma in Relapse
• Multiple Myeloma Progression
• Multiple Myeloma With Failed Remission
• Neoplasms, Plasma Cell

• NCT number: NCT03687125
• Study type: Interventional
• Source: Mundipharma-EDO GmbH
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: October 15, 2018
• Completion date: April 17, 2019