Acute Myelogenous LeukemiaPhase 1/2NCT01486784
A Phase I-II Open Label Non-Randomized Study Using TL32711 for Patients With Acute Myelogenous Leukemia, Myelodysplastic Syndrome and Acute Lymphoblastic Leukemia
A Phase 1/2 study testing Birinapant in people with Acute Myelogenous Leukemia, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial summary
This was initially a phase I/II, open-label non-randomized study using an investigational new drug, TL32711, in patients with AML, MDS and ALL, however, the phase II portion was never initiated. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myelogenous Leukemia
- What is being tested?
- Birinapant
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2011to Apr 2015
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Subjects with a diagnosis of non-M3 AML, Relapsed or refractory ALL or Intermediate Risk 2 or High Risk disease MDS as follows:
- Subjects with a diagnosis of non-M3 AML which meets one of the following criteria:
- Ages 60 or older: Relapsed or refractory after at least one prior therapy for AML
- Ages 60 or older: Newly diagnosed in a patient with a preceding history of myelodysplastic syndrome which has been treated with azacitidine or decitabine and who are not appropriate candidates for aggressive therapy including induction followed by allogeneic stem cell transplantation
- Ages 18-59: Relapsed or refractory disease after failing three prior lines of therapy
- Subjects with a diagnosis of relapsed or refractory ALL: must have failed three prior lines of therapy and be 18 years of age or older.
Show all 11Show fewer
- Subjects with a diagnosis of Intermediate Risk 2 or High Risk disease (as defined by IPSS score):
- Must have failed to respond/intolerant to, or progressed after a hypomethylating agent, and must not be candidates for allogeneic stem cell transplantation
- Life expectancy of at least 4 weeks
- Must have recovered from toxic effects of prior chemotherapy
- Patients must be able to sign consent and be willing and able to comply with scheduled visits, treatment plan and laboratory testing.
Who cannot join
- Cytotoxic chemotherapy (including azacitidine or decitabine) within the past 28 days other than hydroxyurea
- Active participation in any other investigational treatment study for AML.
- ECOG performance status greater than 2
- Uncontrolled intercurrent illness including, but not limited to: uncontrolled ongoing infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- QT interval corrected for heart rate (QTcB) greater than 480 msec (including subjects on medication). Subjects with a ventricular pacemaker for whom QT interval is not measurable may be eligible for enrollment after consultation with the drug manufacturer and study Medical Monitor, and written documentation of this approval.
- Female subjects who are pregnant or breastfeeding
Trial locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
This was initially a phase I/II, open-label non-randomized study using an investigational new drug, TL32711, in patients with AML, MDS and ALL, however, the phase II portion was never initiated. This study initially targeted subjects 60 years of age and older (with non-M3 AML who have relapsed or refractory disease after standard therapy or who are newly diagnosed and subjects 18-59 (relapsed or refractory after failing 3 prior lines of therapy), and then targeted subjects 18 years of age and older with MDS and ALL.
Read the detailed description
This was initially a phase I/II, open-label, non-randomized study using an investigational new drug, TL 32711, in patients with acute myelogenous leukemia. This study targeted subjects 60 years of age and older (with non-M3 AML who have relapsed or refractory disease after standard therapy or who are newly diagnosed and not candidates for standard induction therapy) and subjects 18-59 (relapsed or refractory after failing 3 prior lines of therapy). Subjects would receive the study drug in 4 weeks dosing periods via one of three different treatment schedules (once weekly, twice weekly or three times weekly dosing). They would receive treatment for up to 6 cycles, however treatment may have been extended at the discretion of the study doctor if felt to be in the best interest of the subject. Up to 46 subjects were to be enrolled on this study at the University of Pennsylvania, depending on the number of subjects needed in the Phase I component in order to determine the MTD. The primary objective of the Phase 1 component was to determine the safety and tolerability of TL32711, and the MTD in this patient population. The primary objective of the Phase 2 portion of this study was to further define the safety and tolerability, and provide preliminary efficacy data, however, the Phase II portion was never initiated.
- Conditions
- Acute Myelogenous Leukemia
- Being tested
- Birinapant
- Keywords
- equal to or greater than age 60 years, non-M3 AML, relapsed disease, primary refractory disease, not appropriate or willing candidates for aggressive therapy, AML
- Medical subject headings
- Leukemia, Myeloid, Acute, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BirinapantDrug
Also called TL37211
IV formulation to be given weekly 3 weeks out of 4 week cycle or 4 weeks our of a 4 week cycle as a 30 minute infusion
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 DL1 | Experimental | 26mg/m2/dose IV once per week x 3 weeks of 4 week cycle Receives: Drug: Birinapant |
| Phase 1 DL-1 | Experimental | 17mg/m2 IV/dose once per week x 3 weeks of 4 week cycle Receives: Drug: Birinapant |
| Phase 1 DL-1a | Experimental | 17mg/m2/dose IV twice per week x 3 weeks of 4 week cycle Receives: Drug: Birinapant |
| Phase 1 DL-1b | Experimental | 17mg/m2/dose IV three times per week x 3 weeks of 4 week cycle Receives: Drug: Birinapant |
| Phase 1 DL-1c | Experimental | 22mg/m2/dose IV twice per week x 3 weeks of 4 week cycle Receives: Drug: Birinapant |
| Phase 1 DL-1d | Experimental | 17mg/m2/dose IV twice per week x 3 weeks of 4 week cycle Receives: Drug: Birinapant |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Safety of Birinapant (TL32711) in Subjects With Acute Myeloid Leukemia, Myelodysplastic Syndromes and Acute Lymphoblastic Leukemia. Acute Lymphocytic Leukemia.
Safety of birinapant will be measured as the number of adverse events per dosing level occurring with greater than 5% frequency in the total evaluable subject population. Adverse events are any untoward medical occurrences experienced by research study participants. These events are documented and assessed for severity and relation to the study drug by the treating investigator, using the Common Terminology for Criteria for Adverse Events for severity, and information on known side effects of the study drug for relation.
Measured: First day of study treatment to 30 days after last study treatment. The average length of time for adverse event monitoring was 14 weeks.
Number of Dose Limiting Toxicities Per Dosing Level.
This outcome measure will be defined as the number of dose limiting toxicities per dosing level. Dose limiting toxicities are pre-defined medical events that may be related to the dosing of the study drug. These toxicities are documented and assessed for severity based on pre-defined thresholds, and may result in modification of the study drug dosing.
Measured: First day of study treatment to 30 days after last study treatment. The average length of time for adverse event monitoring was 14 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2011 (estimated)
- Study startNov 2011
- Primary completionNov 2014
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Myelogenous LeukemiaStudies 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Noelle Frey, MD, Principal investigator, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01486784
- Sponsor's protocol ID
- UPCC 15411
- Status last verified
- Jun 2021
- First submitted
- 5 Dec 2011
- Last updated
- 24 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I-II Open Label Non-Randomized Study Using TL32711 for Patients With Acute Myelogenous Leukemia, Myelodysplastic Syndrome and Acute Lymphoblastic Leukemia
- ClinicalTrials.gov ID
- NCT01486784
- Acronym / sponsor ID
- UPCC 15411
- Conditions
- Acute Myelogenous Leukemia
- Keywords
- equal to or greater than age 60 years, non-M3 AML, relapsed disease, primary refractory disease, not appropriate or willing candidates for aggressive therapy, AML
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Study start
- Nov 2011
- Primary completion
- Nov 2014 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 7 Dec 2011 (estimated)
- Results
- Posted 13 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was initially a phase I/II, open-label non-randomized study using an investigational new drug, TL32711, in patients with AML, MDS and ALL, however, the phase II portion was never initiated. This study initially targeted subjects 60 years of age and older (with non-M3 AML who have relapsed or refractory disease after standard therapy or who are newly diagnosed and subjects 18-59 (relapsed or refractory after failing 3 prior lines of therapy), and then targeted subjects 18 years of age and older with MDS and ALL.
Detailed description
This was initially a phase I/II, open-label, non-randomized study using an investigational new drug, TL 32711, in patients with acute myelogenous leukemia. This study targeted subjects 60 years of age and older (with non-M3 AML who have relapsed or refractory disease after standard therapy or who are newly diagnosed and not candidates for standard induction therapy) and subjects 18-59 (relapsed or refractory after failing 3 prior lines of therapy). Subjects would receive the study drug in 4 weeks dosing periods via one of three different treatment schedules (once weekly, twice weekly or three times weekly dosing). They would receive treatment for up to 6 cycles, however treatment may have been extended at the discretion of the study doctor if felt to be in the best interest of the subject. Up to 46 subjects were to be enrolled on this study at the University of Pennsylvania, depending on the number of subjects needed in the Phase I component in order to determine the MTD. The primary objective of the Phase 1 component was to determine the safety and tolerability of TL32711, and the MTD in this patient population. The primary objective of the Phase 2 portion of this study was to further define the safety and tolerability, and provide preliminary efficacy data, however, the Phase II portion was never initiated.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Phase 1 DL1 | Experimental | Drug: Birinapant26mg/m2/dose IV once per week x 3 weeks of 4 week cycle |
| Phase 1 DL-1 | Experimental | Drug: Birinapant17mg/m2 IV/dose once per week x 3 weeks of 4 week cycle |
| Phase 1 DL-1a | Experimental | Drug: Birinapant17mg/m2/dose IV twice per week x 3 weeks of 4 week cycle |
| Phase 1 DL-1b | Experimental | Drug: Birinapant17mg/m2/dose IV three times per week x 3 weeks of 4 week cycle |
| Phase 1 DL-1c | Experimental | Drug: Birinapant22mg/m2/dose IV twice per week x 3 weeks of 4 week cycle |
| Phase 1 DL-1d | Experimental | Drug: Birinapant17mg/m2/dose IV twice per week x 3 weeks of 4 week cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Subjects with a diagnosis of non-M3 AML, Relapsed or refractory ALL or Intermediate Risk 2 or High Risk disease MDS as follows:
- Subjects with a diagnosis of non-M3 AML which meets one of the following criteria:
- Subjects with a diagnosis of relapsed or refractory ALL: must have failed three prior lines of therapy and be 18 years of age or older.
- Subjects with a diagnosis of Intermediate Risk 2 or High Risk disease (as defined by IPSS score):
Key exclusion criteria (6 listed)
- Cytotoxic chemotherapy (including azacitidine or decitabine) within the past 28 days other than hydroxyurea
- Active participation in any other investigational treatment study for AML.
- ECOG performance status greater than 2
- Uncontrolled intercurrent illness including, but not limited to: uncontrolled ongoing infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- QT interval corrected for heart rate (QTcB) greater than 480 msec (including subjects on medication). Subjects with a ventricular pacemaker for whom QT interval is not measurable may be eligible for enrollment after consultation with the drug manufacturer and study Medical Monitor, and written documentation of this approval.
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: TL37211IV formulation to be given weekly 3 weeks out of 4 week cycle or 4 weeks our of a 4 week cycle as a 30 minute infusion | Drug | Phase 1 DL-1, Phase 1 DL-1a, Phase 1 DL-1b, Phase 1 DL-1c, Phase 1 DL-1d, Phase 1 DL1 |
Primary outcome
The Safety of Birinapant (TL32711) in Subjects With Acute Myeloid Leukemia, Myelodysplastic Syndromes and Acute Lymphoblastic Leukemia. Acute Lymphocytic Leukemia.
Time frame: First day of study treatment to 30 days after last study treatment. The average length of time for adverse event monitoring was 14 weeks.
Safety of birinapant will be measured as the number of adverse events per dosing level occurring with greater than 5% frequency in the total evaluable subject population. Adverse events are any untoward medical occurrences experienced by research study participants. These events are documented and assessed for severity and relation to the study drug by the treating investigator, using the Common Terminology for Criteria for Adverse Events for severity, and information on known side effects of the study drug for relation.
Number of Dose Limiting Toxicities Per Dosing Level.
Time frame: First day of study treatment to 30 days after last study treatment. The average length of time for adverse event monitoring was 14 weeks.
This outcome measure will be defined as the number of dose limiting toxicities per dosing level. Dose limiting toxicities are pre-defined medical events that may be related to the dosing of the study drug. These toxicities are documented and assessed for severity based on pre-defined thresholds, and may result in modification of the study drug dosing.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Noelle Frey, MD principal investigator
Abramson Cancer Center at Penn Medicine
1 site 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 in people with Acute Myelogenous Leukemia, run by Abramson Cancer Center at Penn Medicine at 1 site 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 11 inclusion and 6 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: stopped early, as of the sponsor's last update on 24 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Yes. Results are posted in the registry (first posted 13 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
The Safety of Birinapant (TL32711) in Subjects With Acute Myeloid Leukemia, Myelodysplastic Syndromes and Acute Lymphoblastic Leukemia. Acute Lymphocytic Leukemia. (time frame: First day of study treatment to 30 days after last study treatment. The average length of time for adverse event monitoring was 14 weeks.). The study lists 2 primary outcomes in all. 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 24 Jun 2021.