Erlotinib Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

PRIMARY OBJECTIVES:

I. To assess the efficacy of erlotinib (erlotinib hydrochloride) in patients with refractory
or relapsed acute myeloid leukemia (AML).

II. To determine the safety and tolerability of erlotinib in this patient population.

SECONDARY OBJECTIVES:

I. To investigate inhibitory effect of this drug on spleen tyrosine kinase (SYK) and its
down-stream targets such as mitogen-activated protein kinase 8 (JNK), mitogen-activated
protein kinase (MAPK) and mitogen-activated protein kinase 1 (Erk).

II. To evaluate its role in janus kinase (Jak)/signal transducer and activator of
transcription (STAT) pathway and to investigate erlotinib-mediated cell death and/or
differentiation.

III. To quantitate concentrations of plasma erlotinib.

OUTLINE:

Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-28. Courses
repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

Inclusion Criteria:

- Patients with AML who have either been refractory to prior therapy or have relapsed
after prior therapy; patients with myelodysplastic syndromes (MDS) or chronic
myelomonocytic leukemia (CMML) who received therapy with a hypomethylating agent and
progress to AML are eligible if they have received any therapy for MDS and failed
(i.e., lack or loss of response) regardless of whether they have received therapy for
AML or not; the World Health Organization (WHO) classification will be used for AML

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2

- Total bilirubin =< 2 x upper limit of normal (ULN)

- Alanine aminotransferase (ALT) =< 2.5 x ULN

- Creatinine =< 2 x ULN

- Patients must provide written informed consent

- Patients must have been off chemotherapy for 2 weeks prior to entering this study,
unless there is evidence of rapidly progressive disease, and must have recovered from
the clinically significant toxic effects of that therapy to at least grade 1; use of
hydroxyurea for patients with rapidly proliferative disease is allowed before the
start of study therapy and for the first four weeks on therapy

- Patients-both males and females-with reproductive potential (i.e., menopausal for less
than 1 year and not surgically sterilized) must practice effective contraceptive
measures throughout the study; women of childbearing potential must provide a negative
pregnancy test (serum or urine) within 14 days prior to initiation of study

Exclusion Criteria:

- Patients with known allergy or hypersensitivity to erlotinib

- Patients with any other known disease (except carcinoma in-situ) concurrent severe
and/or uncontrolled medical condition (e.g. uncontrolled diabetes; cardiovascular
disease including congestive heart failure New York Heart Association [NYHA] class III
or IV, myocardial infarction within 6 months, and poorly controlled hypertension;
chronic renal failure; or active uncontrolled infection) which, in the opinion of the
investigator could compromise participation in the study

- Patients unwilling or unable to comply with the protocol

- Significant gastrointestinal disorders that may interfere with absorption of erlotinib

- Patients who can receive a stem cell transplant within 4 weeks