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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01332786
• Other study ID #: OZM-029
• Status: Completed
• Phase: Phase 1
• First received: March 31, 2011
• Last updated: April 14, 2015
• Start date: March 2011
• Est. completion date: January 2015

Study information

• Verified date: April 2015
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review CommitteeCanada: Health CanadaUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: January 2015
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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

Locations

Country	Name	City	State
Canada	Princess Margaret Hospital	Toronto	Ontario
United States	The University of Kansas Medical Center	Kansas City	Kansas
United States	University of California, Los Angeles	Los Angeles	California

Sponsors (4)

Lead Sponsor	Collaborator
University Health Network, Toronto	Memorial Sloan Kettering Cancer Center, University of California, Los Angeles, University of Kansas Medical Center

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity evaluated according to CTCAE version 4.03		Reviewed at each visit and assessed at the end of each 3-week cycle	Yes
Secondary	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	No