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

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of lenalidomide when used in combination
with mitoxantrone hydrochloride, etoposide, and cytarabine (MEC) in patients with relapsed or
refractory acute myeloid leukemia (AML).

II. To determine the dose-limiting toxicities (DLTs) of this combination in this patient
population.

SECONDARY OBJECTIVES:

I. To determine whether the combination of lenalidomide priming prior to re-induction
chemotherapy with MEC has clinical activity in patients with relapsed or refractory AML.

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

LENALIDOMIDE PRIMING: Patients receive lenalidomide orally (PO) for 5 or 7 days.

RE-INDUCTION CHEMOTHERAPY: Patients receive etoposide intravenously (IV) over 1 hour,
cytarabine IV over 3 hours, and mitoxantrone hydrochloride IV over 15-30 minutes on days 1-5.
Patients failing to achieve blast count < 5% at 21 days may receive a second course of
induction therapy. Patients achieving complete remission proceed to lenalidomide priming.

LENALIDOMIDE PRIMING: Within 4-6 weeks, patients receive lenalidomide PO for 5 or 7 days and
then proceed to consolidation therapy.

CONSOLIDATION CHEMOTHERAPY: Patients receive etoposide IV over 1 hour, cytarabine IV over 3
hours, and mitoxantrone hydrochloride IV over 15-30 minutes on days 1-4. Treatment repeats
every 28-35 days for up to 2 courses in the absence of disease progression or unacceptable
toxicity.

After completion of study treatment, patients are followed up for 6 months.

Inclusion Criteria:

- Patients eligible include those with diagnosis of AML other than acute promyelocytic
leukemia by World Health Organization (WHO) criteria with relapsed disease after
induction therapy or refractory to induction chemotherapy, as determined by morphology
on bone marrow biopsy; also eligible are patients unwilling to receive standard
induction chemotherapy

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

- Serum creatinine =< 1.5 mg/dL; if serum creatinine > 1.5 mg/dL, then the estimated
glomerular filtrate rate (GFR) must be > 60ml/min/1.73m^2 as calculated by the
Modification of Diet in Renal Disease equation

- Serum bilirubin =< 1.5 x upper limit of normal (ULN) unless elevation is considered to
be secondary to Gilbert's syndrome, hemolysis, or hepatic infiltration by AML

- Aspartate transaminase (AST)/alanine transaminase (ALT) =< 2.5 x ULN

- Alkaline phosphatase =< 2.5 x ULN

- All study participants must be registered into the mandatory Revlimid assistance
(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) 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

Exclusion Criteria:

- Patient must not undergo concomitant radiotherapy, chemotherapy or immunotherapy;
patient must not be in concurrent study with other investigational agents

- Patients who have received prior lenalidomide therapy are not eligible for this study;
further there should be at least a 14-day window from the patient's last prior therapy
before initiation of treatment on clinical trial

- Have other severe concurrent disease or serious organ dysfunction involving the heart,
kidney, liver or other organ system that may place the patient at undue risk to
undergo treatment

- Have significant, uncontrolled active infection

- Pregnant or nursing patients will be excluded from the study

- Known human immunodeficiency virus (HIV) infection