A Phase I-II Open Label Non-Randomized Study Using TL32711 for Patients With Acute Myelogenous Leukemia, Myelodysplastic Syndrome and Acute Lymphoblastic Leukemia

Phase 1

Terminated

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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Phase 1 DL-1b	Birinapant	17mg/m2/dose IV three times per week x 3 weeks of 4 week cycle
Phase 1 DL-1c	Birinapant	22mg/m2/dose IV twice per week x 3 weeks of 4 week cycle
Phase 1 DL-1	Birinapant	17mg/m2 IV/dose once per week x 3 weeks of 4 week cycle
Phase 1 DL1	Birinapant	26mg/m2/dose IV once per week x 3 weeks of 4 week cycle
Phase 1 DL-1a	Birinapant	17mg/m2/dose IV twice per week x 3 weeks of 4 week cycle
Phase 1 DL-1d	Birinapant	17mg/m2/dose IV twice per week x 3 weeks of 4 week cycle

Primary Outcome Measures

Name	Time	Method
Number of Dose Limiting Toxicities Per Dosing Level.	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.
The Safety of Birinapant (TL32711) in Subjects With Acute Myeloid Leukemia, Myelodysplastic Syndromes and Acute Lymphoblastic Leukemia. Acute Lymphocytic Leukemia.	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.

Secondary Outcome Measures