Lenalidomide and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) of lenalidomide following intermediate dose
ARA-C (cytarabine) in relapsed/refractory AML.

SECONDARY OBJECTIVES:

I. Evaluate immune reconstitution in patients in complete remission (CR) treated at the MTD.

II. Evaluate the efficacy of the regimen in the expanded group treated at the MTD.

OUTLINE: This is a dose-escalation study of lenalidomide.

Patients receive lenalidomide orally (PO) on days 6-26 and cytarabine intravenously (IV) over
3 hours on days 1-5. Treatment repeats every 28 days for up to 2 courses in the absence of
disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 2 weeks and then every 3
months thereafter.

Inclusion Criteria:

- Patient with relapsed/refractory AML for which no standard effective therapy is
anticipated to result in a durable partial or complete remission

- Eastern Cooperative Oncology Group Performance (ECOG) status 0-2

- Bilirubin =< 2.5 x upper limit of normal (ULN) unless considered Gilbert's syndrome of
leukemia

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
unless considered Gilbert's syndrome of leukemia

- Partial thromboplastin time (PTT) must be < 1.5 x ULN and international normalized
ratio (INR) < 1.5 ULN

- Phase I subjects must have calculated creatinine clearance >= 50 ml/min by
Cockcroft-Gault formula

- All study participants must be registered into the mandatory RevAssist program, and be
willing and able to comply with the requirements of RevAssist

- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
test with a sensitivity of at least 50 mIU/mL within 10-14 days and again within 24
hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled
within 7 days as required by RevAssist) of lenalidomide and must either commit to
continued abstinence from heterosexual intercourse or begin TWO acceptable methods of
birth control, one highly effective method and one additional effective method AT THE
SAME TIME, at least 28 days before she starts taking lenalidomide; FCBP must also
agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual
contact with a FCBP even if they have had a successful vasectomy; all patients must be
counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal
exposure; men must agree to use a latex condom during sexual contact with a FCBP even
if they have had a successful vasectomy; all patients must be counseled at a minimum
of every 28 days about pregnancy precautions and risks of fetal exposure

- Patient is capable of understanding and complying with parameters as outlined in the
protocol and able to sign informed consent

- For patients with thromboembolic risk (history of deep venous thrombosis
[DVT]/pulmonary embolism [PE], on medications that increase risk of thrombolic event,
etc.) able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation
(patients intolerant to aspirin [ASA] may use warfarin or low molecular weight
heparin); the risk of blood clots may also be increased when lenalidomide is combined
with other drugs known to cause blood clots such as steroids, other forms of cancer
drugs, hormone replacement therapy, birth control pills and erythropoietin

Exclusion Criteria:

- Known active central nervous system (CNS) disease

- The patient has received any anti-cancer therapy including chemotherapy,
immunotherapy, radiotherapy, hormonal, biologic or any investigational agents within
14 days or 5 half lives, whichever is greater, prior to drug administration on this
study or has not recovered to less than grade 2 clinically significant
non-hematological adverse effects/toxicities of the previous therapy except
hydroxyurea up to 24 hours prior to cytarabine initiation

- The patient has a documented left ventricular ejection fraction of < 50 %

- Active uncontrolled infection

- Symptomatic congestive heart failure

- Unstable angina pectoris or cardiac arrhythmia

- History of adrenal insufficiency

- Psychiatric illness/social situation that would limit compliance with study
requirements

- Known seropositive for or active viral infection with human immunodeficiency virus
(HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); patients who are
seropositive because of hepatitis B virus vaccine are eligible

- Any medical condition which in the opinion of the study investigator places the
patient at an unacceptable high risk of toxicities

- Lactating or pregnant female (Lactating females must agree not to breast feed while
taking lenalidomide)

- The development of erythema nodosum if characterized by a desquamating rash while
taking thalidomide or similar drugs

- Any prior use of lenalidomide

- Concurrent use of other anti-cancer agents or treatments or any other investigational
agent except hydroxyurea up to 24 hours prior to cytarabine initiation