Mitoxantrone, Etoposide, and Cytarabine (MEC) Plus Lenalidomide for Relapsed or Refractory Acute Myeloid Leukemia

This research study is a Phase II clinical trial. Phase II clinical trials test the safety
and effectiveness of an investigational intervention to learn whether the intervention works
in treating a specific disease. "Investigational" means that the intervention is being
studied.

The FDA (the U.S. Food and Drug Administration) has not approved lenalidomide for this
specific disease, but it has been approved for other uses, including for patients with
multiple myeloma and some patients with myelodysplastic syndrome. This treatment is
investigational because it is not approved by the FDA for patients with AML. Lenalidomide is
a chemotherapy that also modulates the immune system, and is in a category of drugs called
immunomodulatory drugs or IMIDs. Some research studies suggest that lenalidomide may be
effective in patients with AML. Since the investigators know that many patients who receive
MEC chemotherapy alone have less than desired response rates and overall shorter periods of
remission (time free from leukemia) after treatment, the investigators are studying whether
the addition of lenalidomide to MEC improves upon typical responses.

The combination of MEC (mitoxantrone, etoposide, and cytarabine) is a standard treatment
option, commonly used for relapsed or refractory acute myeloid leukemia.

Inclusion Criteria:

- Acute myelogenous leukemia diagnosed by WHO criteria with one of the following
(patients with biphenotypic leukemia are eligible, provided that the treating
physician determines an AML treatment regimen is appropriate)

- Primary refractory disease following > 1cycle of chemotherapy, (such as
hypomethylating agent or induction chemotherapy)

- First relapse or higher. Patients with primary or secondary acute myelogenous
leukemia are eligible.

- Age 18-70 years old

- LVEF > 50 %

- ECOG Performance status 0-2

- Able to adhere to study schedule and other protocol requirements.

- Participants must have normal organ function as defined below, unless felt due to
underlying disease and approved by the overall PI. Patients with Gilbert's disease may
have total bilirubin up to < 3 x ULN.

- Creatinine < 2.0mg/dl

- Total bilirubin < 1.5 x ULN

- AST (SGOT) and ALT (SGPT) < 3 x ULN.

- Patients may receive hydroxyurea, steroids, or leukapheresis as necessary until Day 5
of treatment.

- Patients must give voluntary written informed consent and HIPAA authorization before
performance of any study-related procedure not part of normal medical care, with the
understanding that consent may be withdrawn by the subject at any time without
prejudice to future medical care.

- Patients may have had prior treatment for MDS or AML, including prior lenalidomide for
MDS or AML or another condition.

- Patient may have had prior autologous or allogeneic transplant (family member,
unrelated donor, or cord blood) if there is at least 90 days between transplant and
study entry.

- Patients may also have had donor lymphocyte infusion if there is at least 60 days
between donor lymphocyte infusion and study entry.

- Patients on immunosuppression are also eligible.

- Females of childbearing potential (FCBP)† must have a negative serum or urine
pregnancy test with a sensitivity of at least 50 mIU/mL prior to receiving treatment
with 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.

- Ability to understand and the willingness to sign a written informed consent document.

- All study participants must be registered into the mandatory Revlimid REMS ® program,
and be willing and able to comply with the requirements of the REMs ® program. Females
of reproductive potential must adhere to the scheduled pregnancy testing as required
in the Revlimid REMS® program

Exclusion Criteria:

- Known hypersensitivity to thalidomide or lenalidomide (if applicable).

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

- Known seropositive for human immunodeficiency virus (HIV). HIV testing is not
required. Hepatitis testing is not required.

- Patients who have had a myocardial infarction within 6 months of enrollment or has New
York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina,
uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
ischemia or active conduction system abnormalities.

- Any serious medical condition laboratory abnormality or psychiatric illness that would
prevent the subject from signing the consent form.

- Any condition, including laboratory abnormalities, that in the opinion of the
investigator places the subject at unacceptable risk if he/she were to participate in
the study or confounds the ability to interpret data from the study.

- Patients with major surgery within 28 days prior to treatment.

- Patients with any serious medical or psychiatric illness that could, in the
investigator's opinion, potentially interfere with the completion of treatment
according to this protocol.

- Patient has received an investigational agent or cytotoxic chemotherapy (excluding
hydroxyurea) within 7 days of study entry.

- Patients with acute promyelocytic leukemia.

- Females who are pregnant