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

NCT01828346 | Completed Phase 1

• 1 other identifier: TL32711-0087
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Myelodysplastic Syndrome

Keywords

TL32711; Birinapant; 5-Azacitidine; Myelodysplastic syndrome; MDS; Relapsed; Refractory; Failed; open-label; non-Randomized; dose-escalation; dose-expansion

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  6 months

Study Arms (1)

Treatment

EXPERIMENTAL

5-Azacitidine plus birinapant

Drug: Birinapant; Drug: 5-Azacitidine

Interventions

Birinapant DRUG

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)

Also known as: TL32711

Treatment

5-Azacitidine DRUG

Dose Level (0) - 75mg/m2 daily

Also known as: 5-AZA

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• TetraLogic Pharmaceuticals: lead

Study Sites (7)

Palo Verde Hematology Oncology

Glendale, Arizona, 85304, United States

Location

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259, United States

Location

California Cancer Associates for Research and Excellence

Fresno, California, 93720, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Recurrence

Interventions

birinapant; Azacitidine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Gautam Borthakur, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2013
• First Posted: April 10, 2013
• Study Start: June 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: November 1, 2015
• Last Updated: April 21, 2016

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)