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

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.

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