Back to resultsA Phase I-II Open Label Non-Randomized Study Using TL32711 for Patients With Acute Myelogenous Leukemia, Myelodysplastic Syndrome and Acute Lymphoblastic Leukemia
Primary Purpose
Acute Myelogenous Leukemia
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Birinapant
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myelogenous Leukemia focused on measuring 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
Eligibility Criteria
Inclusion criteria
- 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.
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.
Exclusion criteria
- 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
Sites / Locations
- Abramson Cancer Center of the University of Pennsylvania
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Phase 1 DL1
Phase 1 DL-1
Phase 1 DL-1a
Phase 1 DL-1b
Phase 1 DL-1c
Phase 1 DL-1d
Arm Description
26mg/m2/dose IV once per week x 3 weeks of 4 week cycle
17mg/m2 IV/dose once per week x 3 weeks of 4 week cycle
17mg/m2/dose IV twice per week x 3 weeks of 4 week cycle
17mg/m2/dose IV three times per week x 3 weeks of 4 week cycle
22mg/m2/dose IV twice per week x 3 weeks of 4 week cycle
17mg/m2/dose IV twice per week x 3 weeks of 4 week cycle
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT01486784
First Posted
December 5, 2011
Last Updated
June 23, 2021
Sponsor
Abramson Cancer Center at Penn Medicine
1. Study Identification
Unique Protocol Identification Number
NCT01486784
Brief Title
A Phase I-II Open Label Non-Randomized Study Using TL32711 for Patients With Acute Myelogenous Leukemia, Myelodysplastic Syndrome and Acute Lymphoblastic Leukemia
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Terminated
Study Start Date
November 2011 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
April 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Abramson Cancer Center at Penn Medicine
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase 1 DL1
Arm Type
Experimental
Arm Description
26mg/m2/dose IV once per week x 3 weeks of 4 week cycle
Arm Title
Phase 1 DL-1
Arm Type
Experimental
Arm Description
17mg/m2 IV/dose once per week x 3 weeks of 4 week cycle
Arm Title
Phase 1 DL-1a
Arm Type
Experimental
Arm Description
17mg/m2/dose IV twice per week x 3 weeks of 4 week cycle
Arm Title
Phase 1 DL-1b
Arm Type
Experimental
Arm Description
17mg/m2/dose IV three times per week x 3 weeks of 4 week cycle
Arm Title
Phase 1 DL-1c
Arm Type
Experimental
Arm Description
22mg/m2/dose IV twice per week x 3 weeks of 4 week cycle
Arm Title
Phase 1 DL-1d
Arm Type
Experimental
Arm Description
17mg/m2/dose IV twice per week x 3 weeks of 4 week cycle
Intervention Type
Drug
Intervention Name(s)
Birinapant
Other Intervention Name(s)
TL37211
Intervention Description
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
Primary Outcome Measure Information:
Title
The Safety of Birinapant (TL32711) in Subjects With Acute Myeloid Leukemia, Myelodysplastic Syndromes and Acute Lymphoblastic Leukemia. Acute Lymphocytic Leukemia.
Description
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.
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.
Title
Number of Dose Limiting Toxicities Per Dosing Level.
Description
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.
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria
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.
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.
Exclusion criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Noelle Frey, MD
Organizational Affiliation
Abramson Cancer Center at Penn Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Abramson Cancer Center of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Phase I-II Open Label Non-Randomized Study Using TL32711 for Patients With Acute Myelogenous Leukemia, Myelodysplastic Syndrome and Acute Lymphoblastic Leukemia
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