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

NCT ID: NCT01332786

Last Updated: 2015-04-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2015-01-31

Brief 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.

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.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tigecycline

Group Type: EXPERIMENTAL

Tigecycline

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

Tygacil

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Kansas

OTHER

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Aaron Schimmer, MD

Role: STUDY_DIRECTOR

University Health Network, Toronto

Locations

University of California, Los Angeles

Los Angeles, California, United States

The University of Kansas Medical Center

Kansas City, Kansas, United States

Princess Margaret Hospital

Toronto, Ontario, Canada

Countries

United States; Canada

Other Identifiers

OZM-029

Identifier Type: -

Identifier Source: org_study_id