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

• Status: Completed
• Trial end date: 2015-11-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: TetraLogic Pharmaceuticals
• Treatments: Azacitidine

Criteria

Inclusion Criteria:

• Men or women more than 18 years of age.

• Patients with high-risk Myelodysplastic Syndrome

• Performance status of greater or equal to 2 by the Eastern Cooperative Oncology Group (ECOG) scale.

• Subjects with high-risk MDS who are naïve to 5-Azacitidine or have previously received 5-AZA or decitabine as first-line cytotoxic therapy. Subjects with prior 5-Azacitidine therapy were evaluated to be either refractory or relapsed as determined by the Investigator, according to IWG response criteria.Subjects with relapsed or refractory disease may have only received prior 5-Azacitidine or decitabine.

• Hydroxyurea for patients with rapidly proliferative disease can be used up to 24 hours prior to therapy but not concomitantly with 5-Azacitidine.

• Adequate liver, pancreatic and renal function.

• Women of childbearing potential must have a negative serum pregnancy test at screening within 48 hours prior to the first dose

• Women of childbearing potential must agree to use 2 methods of adequate contraception

Exclusion Criteria:

• Subjects with life-threatening toxicity or non tolerability to prior 5-Azacitidine therapy.

• Subjects with hypoplastic Myelodysplastic syndrome.

• Subjects with >30% bone marrow blast cells.

• Subjects with malignant hepatic tumors or secondary malignancy within 2 years

• Known diagnosis of human immunodeficiency virus or chronic active Hepatitis B or C.

• Uncontrolled hypertension

• Impaired cardiac function, uncontrolled cardiac arrhythmias despite medications,

• QT interval corrected for heart rate (QTcB) more than 480 msec

• Lack of recovery of prior adverse events to Grade ≤1 severity (National Cancer Institute Common Terminology Criteria for Adverse Events version 4) (except alopecia) due to therapy administered prior to the initiation of study drug dosing.

• Nursing or pregnant women.

• Known allergy to any of the formulation components of birinapant.

• Known or suspected hypersensitivity to 5-Azacitidine or mannitol.

• Any concurrent disease and/or medical condition that, in the opinion of the Investigator, would prevent the subject's participation.

• History of Bell's Palsy.