Trial record 1 of 1 for:    NCT01828346
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Birinapant With 5-azacitidine in MDS Subjects Who Are Naïve, Have Relapsed or Are Refractory to 5-azacitidine Therapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by TetraLogic Pharmaceuticals
Sponsor:
Information provided by (Responsible Party):
TetraLogic Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01828346
First received: April 5, 2013
Last updated: August 13, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Myelodysplastic Syndrome
Drug: TL32711
Drug: 5-Azacitidine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by TetraLogic Pharmaceuticals:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 45
Study Start Date: June 2013
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: TL32711

    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)
    Other Name: Birinapant
    Drug: 5-Azacitidine
    Dose Level (0) - 75mg/m2 daily
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01828346

Contacts
Contact: Minal Mehta, MBBS 610-889-9900 ext 111 minal.mehta@tetralogicpharma.com

Locations
United States, Arizona
Palo Verde Hematology Oncology Recruiting
Glendale, Arizona, United States, 85304
Contact    602-978-6255      
Principal Investigator: Amol Nanak S. Rakkar, MD         
Mayo Clinic Scottsdale Recruiting
Scottsdale, Arizona, United States, 85259
Contact    480-301-8335      
Principal Investigator: Raoul Tibes, MD, PhD         
United States, California
California Cancer Associates for Research and Excellence Recruiting
Fresno, California, United States, 93720
Contact    559-326-1222      
Principal Investigator: Steven J. Hager, DO         
United States, Florida
Mayo Clinic Jacksonville Recruiting
Jacksonville, Florida, United States, 32224
Contact    904-953-7292      
Principal Investigator: James Foran, MD         
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact    716-845-3544      
Principal Investigator: Eunice S. Wang, MD         
United States, Pennsylvania
University of Pennsylvania, Abramson Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact    855-216-0098      
Principal Investigator: Noelle Frey, MD         
United States, Texas
The University of Texas M.D. Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact    713-563-1586      
Principal Investigator: Gautam Borthakur, MD         
Sponsors and Collaborators
TetraLogic Pharmaceuticals
  More Information

No publications provided

Responsible Party: TetraLogic Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01828346     History of Changes
Other Study ID Numbers: TL32711-0087
Study First Received: April 5, 2013
Last Updated: August 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by TetraLogic Pharmaceuticals:
TL32711
Birinapant
5-Azacitidine
Myelodysplastic syndrome
MDS
Relapsed
Refractory
Failed
open-label
non-Randomized
dose-escalation
dose-expansion

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Disease
Pathologic Processes
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014