NCT01828346

Birinapant With 5-azacitidine in MDS Subjects Who Are Naïve, Have Relapsed or Are Refractory to 5-azacitidine Therapy

A Phase 1b/2a, Open-label, Non-randomized Study of Birinapant in Combination With 5-azacitidine in Subjects With Myelodysplastic Syndrome Who Are Naïve, Refractory or Have Relapsed to 5-azacitidine Therapy

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 21 (actual)
• Sponsor: TetraLogic Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a dose escalation followed by dose expansion study of TL32711 in combination with 5-Azacitidine in subjects with Myelodysplastic syndrome who are naïve, have relapsed or have failed prior 5-azacitidine therapy. Pre-clinical and mechanistic studies support that 5-Azacitidine may modulate pathways that enable birinapant-mediated anti-tumor activity.

Detailed description

This is a Phase 1b/2a, open-label, non-randomized study in male and female subjects with MDS who are naïve, refractory or have relapsed to 5-Azacitidine therapy. Primary Objective is to determine the maximum tolerated dose (MTD), recommended Phase 2 dose, and pharmacodynamics (PD) of birinapant (TL32711) when administered in combination with 5-azacitidine (5 AZA) in subjects with myelodysplastic syndrome (MDS) who are naïve, refractory or have relapsed to 5-AZA therapy. Secondary Objectives are to determine the clinical activity using the International Working Group (IWG) (Cheson, 2006) Response Criteria for MDS during the Phase 1b dose escalation stage of the study and in the Phase 2a expansion cohort, to determine the pharmacokinetics (PK) of birinapant when administered with 5-AZA in plasma and to assess exploratory translational biomarkers of anti-tumor activity of birinapant in combination therapy.

Conditions

• Myelodysplastic Syndrome

Interventions

Type	Name	Description
DRUG	Birinapant	Dose escalation part: (Drug escalation dose levels) * Dose Level (1) - 13mg/m2 (twice a week for 3 of 4 weeks) * Dose Level (-1) - 11 mg/m2 (twice a week for 3 of 4 weeks) * Dose Level (2) - 13mg/m2 (twice weekly x 4 weeks) * Dose Level (3a) - 17mg/m2 (twice weekly × 4 weeks)OR * Dose Level (3b) - 17mg/m2 (twice a week for 3 of 4 weeks)
DRUG	5-Azacitidine	Dose Level (0) - 75mg/m2 daily

Timeline

• Start date: 2013-06-01
• Primary completion: 2015-06-01
• Completion: 2015-11-01
• First posted: 2013-04-10
• Last updated: 2016-04-21

Locations

7 sites across 1 country: United States