NCT03687125

Tinostamustine Conditioning and Autologous Stem Cell

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
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 6 (actual)
• Sponsor: Mundipharma-EDO GmbH · Industry
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

• Multiple Myeloma in Relapse
• Multiple Myeloma Progression
• Multiple Myeloma With Failed Remission

Interventions

Type	Name	Description
DRUG	Tinostamustine	Participants received tinostamustine IV injection.
PROCEDURE	Autologous Stem Cell Transplant (ASCT)	Undergo autologous stem cell transplant

Timeline

• Start date: 2018-10-15
• Primary completion: 2019-04-17
• Completion: 2019-04-17
• First posted: 2018-09-27
• Last updated: 2021-06-18
• Results posted: 2021-06-18

Locations

12 sites across 3 countries: United States, Norway, Switzerland

Regulatory

• FDA-regulated drug study