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

NCT01486784 | Terminated Phase 1 Results DMC

• 1 other identifier: UPCC 15411
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  First day of study treatment to 30 days after last study treatment. The average length of time for adverse event monitoring was 14 weeks.

Study Arms (6)

Phase 1 DL1

EXPERIMENTAL

26mg/m2/dose IV once per week x 3 weeks of 4 week cycle

Drug: Birinapant

Phase 1 DL-1

EXPERIMENTAL

17mg/m2 IV/dose once per week x 3 weeks of 4 week cycle

Drug: Birinapant

Phase 1 DL-1a

EXPERIMENTAL

17mg/m2/dose IV twice per week x 3 weeks of 4 week cycle

Drug: Birinapant

Phase 1 DL-1b

EXPERIMENTAL

17mg/m2/dose IV three times per week x 3 weeks of 4 week cycle

Drug: Birinapant

Phase 1 DL-1c

EXPERIMENTAL

22mg/m2/dose IV twice per week x 3 weeks of 4 week cycle

Drug: Birinapant

Phase 1 DL-1d

EXPERIMENTAL

17mg/m2/dose IV twice per week x 3 weeks of 4 week cycle

Drug: Birinapant

Interventions

Birinapant DRUG

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

Also known as: TL37211

Phase 1 DL-1; Phase 1 DL-1a; Phase 1 DL-1b; Phase 1 DL-1c; Phase 1 DL-1d; Phase 1 DL1

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Interventions

birinapant

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Noelle Frey
• Organization: Abramson Cancer Center at the University of Pennsylvania

noelle.frey@pennmedicine.upenn.edu

Study Officials

• Noelle Frey, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: December 5, 2011
• First Posted: December 7, 2011
• Study Start: November 1, 2011
• Primary Completion: November 1, 2014
• Study Completion: April 1, 2015
• Last Updated: June 24, 2021
• Results First Posted: May 13, 2021

Record last verified: 2021-06

Locations

US (1)