Safety Study Evaluating Intravenous Infusions of Tigecycline to Treat Acute Myeloid Leukemia

Phase 1 Study Evaluating the Tolerance and Biologic Activity of Intravenous Infusions of Tigecycline in Patients With Relapsed or Refractory AML

The purpose of this study is to determine whether tigecycline is safe and which dosage is most effective in the treatment of patients with acute myeloid leukemia.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Tigecycline

Detailed Description

Relapsed and refractory hematologic malignancies have poor responses to standard therapy and are associated with a poor prognosis. For example, relapsed acute myeloid leukemia (AML) is a highly aggressive and resistant disease, particularly when associated with first complete response (CR) duration of less than 12 months. Thus, there is an urgent need for new agents in relapsed and refractory hematologic malignancies such as acute leukemia. In elderly patients, where the tolerance of aggressive induction therapy is often poor and curative options such as bone marrow transplantation HSCT are not available, the need for effective non-aggressive drug regimens for AML is even greater.

Tigecycline is a glycylcycline derivative of tetracycline. Tigecycline is currently indicated for the treatment of complicated skin and skin structure infections, and complicated intra-abdominal infections. This clinical trial is a Phase I dose escalation study of tigecycline in patients with relapsed or refractory AML or those with newly diagnosed disease not eligible for induction chemotherapy.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age >18 years
• Diagnosis of relapsed or refractory AML for which all potentially curative or standard salvage therapy options have been exhausted; OR AML without prior treatment who are not eligible for induction chemotherapy as defined as age > or equal to 80 or age > 70 with poor risk cytogenetics (3 or more abnormalities, -5/del(5q), 3q abnormalities, or -7) or stable co-morbidities that would preclude induction chemotherapy such as LVEF less than 40% and/or DlCO less than 60% expected
• ECOG 0-2 performance status
• Biochemical values within the following range
• Serum creatinine <2x upper limit of normal
• Total bilirubin <1.5x upper limit of normal
• AST and ALT <2x upper limit of normal
• Recovery from non-hematologic toxicity from prior chemotherapy
• Able and willing to provide informed consent

Exclusion Criteria:

• Allergy to tetracycline or minocycline
• Uncontrolled intercurrent illness such as uncontrolled diabetes or active uncontrolled infection
• Active systemic bacterial, fungal, or viral infection
• Concomitant use of linezolid or chloramphenicol that are known to inhibit mitochondrial protein synthesis
• Pregnant or breast feeding
• Known active CNS involvement with AML
• Neurologic symptoms related to uncontrolled illnesses or unexplained causes
• Psychiatric illness that would limit compliance with study
• Receiving systemic chemotherapy other than hydroxyurea to control circulating blast counts. Concomitant hydroxyurea is permitted, but only in the first cycle of therapy
• Prior therapy with tigecycline as an anti-cancer therapy or any use of the drug in the last month
• Use of other investigational anti-leukemic therapy within 14 days of registration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Tigecycline

Drug: Tigecycline; Dosage Form: one-hour intravenous infusion Dosage levels, frequency, duration: (3-week cycles); Level 1: 50 mg daily x 10 doses; 1 week rest; Level 2: 100 mg daily x 10 doses; 1 week rest; Level 3: 150 mg daily x 10 doses; 1 week rest; Level 4: 200 mg daily x 10 doses 1 week rest; Level 5: 250 mg daily x 10 doses; 1 week rest; Level 6: 300 mg daily x 10 doses; 1 week rest; Level 7: 350 mg daily x 10 doses; 1 week rest; Other Names: Tygacil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Toxicity evaluated according to CTCAE version 4.03	Reviewed at each visit and assessed at the end of each 3-week cycle

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate assessment of tigecycline through laboratory assessments	Bone marrow assessment, absolute neutrophil count, platelet counts	Assessed at the end of each 3-week cycle for the study duration

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: Memorial Sloan Kettering Cancer Center; University of California, Los Angeles; University of Kansas
• Investigators: Study Director: Aaron Schimmer, MD, University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: March 31, 2011
• First Submitted That Met QC Criteria: April 7, 2011
• First Posted (Estimate): April 11, 2011

Study Record Updates

• Last Update Posted (Estimate): April 15, 2015
• Last Update Submitted That Met QC Criteria: April 14, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: AML
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Tigecycline
• Other Study ID Numbers: OZM-029