Study of Tinostamustine, First-in-Class Alkylating HDACi Fusion Molecule, in Relapsed/Refractory Hematologic Malignancies
Last updated on July 2021Recruitment
- Recruitment Status
- Recruiting
- Estimated Enrollment
- 84
Summary
- Conditions
- Cutaneous T Cell Lymphoma
- Hematological Malignancies
- Hodgkin's Lymphoma
- Multiple Myeloma
- Type
- Interventional
- Phase
- Phase 1
- Design
- Allocation: N/AIntervention Model: Single Group AssignmentMasking: None (Open Label)Primary Purpose: Treatment
Participation Requirements
- Age
- Between 18 years and 125 years
- Gender
- Both males and females
Description
Tinostamustine is a new chemical entity, a first-in-class fusion molecule of an alkylator, bendamustine and a histone-deacetylase inhibitor (HDACi), vorinostat. It is anticipated that tinostamustine may have activity in various hematological malignancies and solid tumors. The study consists of 2 sta...
Tinostamustine is a new chemical entity, a first-in-class fusion molecule of an alkylator, bendamustine and a histone-deacetylase inhibitor (HDACi), vorinostat. It is anticipated that tinostamustine may have activity in various hematological malignancies and solid tumors. The study consists of 2 stages: Stage 1: Dose Escalation to determine Maximum Tolerated Dose (MTD) at the optimal infusion time and the pharmacokinetic (PK) profiles; is expected to enroll between 21 and 48 patients. Stage 1 has now been completed. Stage 2: Expansion in five Cohorts, in which approximately 12-16 patients will be enrolled per cohort, for a maximum of 70 patients. In Stage 1, tinostamustine doses were escalated following the standard 3+3 design. The decision to escalate to the next dose level occurred after all cohort patients completed 3 weeks (21 days) of observation and have been evaluated for safety and toxicity.The starting dose was a 1 hour infusion of 20 mg/m2, and the maximum dose level was 150 mg/m2. Reduced infusion times of 45 minutes and 30 minutes were assessed once the maximum tolerated dose at a 1-hour infusion was determined. In Stage 2, five cohorts of patients (with relapsed/refractory multiple myeloma (MM); relapsed/refractory Hodgkin's lymphoma; relapsed/refractory peripheral T-cell lymphoma (PTCL); relapsed/refractory cutaneous T-cell lymphoma (CTCL); and relapsed/refractory T-cell Prolymphocytic leukemia (T-PLL) will be enrolled and treated at the recommended Phase 2 dose (RP2D) based on results of Stage 1. For MM patients, treatment will occur on Day 1 and Day 15 of a 28 day cycle. For lymphoma patients, treatment will occur on Day 1 of a 21 day cycle. Patients in each stage of the study are expected to receive a median of four Cycles of therapy, and the maximum number of treatment Cycles allowed is 12.
Tracking Information
- NCT #
- NCT02576496
- Collaborators
- Not Provided
- Investigators
- Principal Investigator: Pier L Zinzani, MD,PhD University of Bologna Medical Center, Bologna