Myelodysplastic SyndromePhase 1/2NCT01828346
Birinapant With 5-azacitidine in MDS Subjects Who Are Naïve, Have Relapsed or Are Refractory to 5-azacitidine Therapy
A Phase 1/2 study testing Birinapant and 5-Azacitidine in people with Myelodysplastic Syndrome, run by TetraLogic Pharmaceuticals at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome
- What is being tested?
- Birinapant and 5-Azacitidine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 7 sitesUnited States
- Study dates
- Jun 2013to Nov 2015
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Roswell Park Cancer Institute
Buffalo, New York, 14263
California Cancer Associates for Research and Excellence
Fresno, California, 93720
Palo Verde Hematology Oncology
Glendale, Arizona, 85304
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, 77030
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224
University of Pennsylvania, Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
Mayo Clinic Scottsdale
Scottsdale, Arizona, 85259
About this study
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
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.
Read the 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
- Being tested
- Birinapant, 5-Azacitidine
- Keywords
- TL32711, Birinapant, 5-Azacitidine, Myelodysplastic syndrome, MDS, Relapsed, Refractory, Failed, open-label, non-Randomized, dose-escalation, dose-expansion
- Medical subject headings
- Myelodysplastic Syndromes, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BirinapantDrug
Also called 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)
5-AzacitidineDrug
Also called 5-AZA
Dose Level (0) - 75mg/m2 daily
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | 5-Azacitidine plus birinapant Receives: Drug: Birinapant; Drug: 5-Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD)
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2013 (estimated)
- Study startJun 2013
- Primary completionJun 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- TetraLogic Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gautam Borthakur, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01828346
- Sponsor's protocol ID
- TL32711-0087
- Status last verified
- Apr 2016
- First submitted
- 5 Apr 2013
- Last updated
- 21 Apr 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01828346
- Acronym / sponsor ID
- TL32711-0087
- Conditions
- Myelodysplastic Syndrome
- Keywords
- TL32711, Birinapant, 5-Azacitidine, Myelodysplastic syndrome, MDS, Relapsed, Refractory, Failed
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- TetraLogic PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jun 2013
- Primary completion
- Jun 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 10 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Birinapant, Drug: 5-Azacitidine5-Azacitidine plus birinapant |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BirinapantAlso: TL32711Dose 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 | Treatment |
| 5-AzacitidineAlso: 5-AZADose Level (0) - 75mg/m2 daily | Drug | Treatment |
Primary outcome
Maximum tolerated dose (MTD)
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2016.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gautam Borthakur, MD principal investigator
M.D. Anderson Cancer Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Birinapant and 5-Azacitidine in people with Myelodysplastic Syndrome, run by TetraLogic Pharmaceuticals at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2016.