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


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Myelodysplastic Syndrome

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Trial Information

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


This is a Phase 1b/2a, open-label, non-randomized study in male and female subjects with MDS
who are 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
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.


Inclusion Criteria:



- Men or women more than18 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.

- 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 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 advanced malignant hepatic tumors or second 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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose (MTD)

Outcome Time Frame:

6 months

Safety Issue:

Yes

Authority:

United States: Food and Drug Administration

Study ID:

TL32711-0087

NCT ID:

NCT01828346

Start Date:

May 2013

Completion Date:

June 2014

Related Keywords:

  • Myelodysplastic Syndrome
  • TL32711
  • Birinapant
  • 5-Azacitidine
  • Myelodysplastic syndrome
  • MDS
  • Relapsed
  • Refractory
  • Failed
  • open-label
  • non-Randomized
  • dose-escalation
  • dose-expansion
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location

Miami, Florida  33176
Tetralogic research siteScottsdale, Arizona  85259
Tetralogic research siteBuffalo, New York  14263
Tetralogic research sitePhiladelphia, Pennsylvania  19104
Tetralogic research siteHouston, Texas  77030