Lenalidomide as Consolidation and Maintenance in Adults >/= 60 Years of Age With AML Following Standard Induction

This study is a single-arm, open-label phase Ib clinical trial testing the hypothesis that
the daily use of lenalidomide will be safe and tolerable as evidenced by the rate of
dose-limiting toxicity (DLT) seen during one month of reinduction/consolidation in older (≥
60 years of age) acute myeloid leukemia (AML) patients treated after one cycle of
conventional, anthracycline-based induction. (Re-induction is the prescribed lenalidomide
therapy given to patients who are in partial remission/response post induction while
consolidation is the same prescribed lenalidomide therapy post induction given to patients
who are in complete remission).

Dose escalation will take place within cohorts during the 28-day re-induction/ consolidation
lenalidomide treatment at the University of North Carolina at Chapel Hill. After
re-induction/consolidation, patients who harbor ≥ 5% peripheral blood or bone marrow
myeloblasts will be removed from protocol therapy. Patients who have <5% peripheral blood or
bone marrow myeloblasts after consolidation therapy will be allowed to continue to
maintenance therapy: lenalidomide 10 mg/day continuously for up to 12 months. Up to 26
patients will be enrolled.

This trial includes a Geriatric Assessment (GA) of each enrolled patient at baseline and
serially across the trial. The investigators also plan to study natural killer (NK) cell
phenotype and cytolytic function in patients at various intervals across the study (baseline,
post re-induction/consolidation, and during maintenance.

Inclusion Criteria:

- Patients ≥60 years of age with AML

- Patients with therapy-related myeloid neoplasms are allowed

- Patients with AML that has evolved from an antecedent hematologic disorder are
allowed

- Patients will be eligible regardless of their ultimate plans or candidacy for
allogeneic stem cell transplant

- 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; see definition below) must have a negative
serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14
days and again within 24 hours prior to prescribing lenalidomide for
re-induction/consolidation (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.

- A FCBP is a sexually mature female who: 1) has not undergone a hysterectomy or
bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least
24 consecutive months (i.e., has had menses at any time in the preceding 24
consecutive months).

- Men must agree to use a latex condom during sexual contact with a FCBP even if they
have had a successful vasectomy. See Appendix C: Risks of Fetal Exposure, Pregnancy
Testing Guidelines and Acceptable Birth Control Methods.

- Patients must have been treated with 1-2 courses of intensive therapy as first therapy
for AML, commonly described as induction. These therapies should include cytarabine at
a dose ≥700 mg/m2 in combination with an anthracycline or anthracenedione (≥ 135 mg/m2
of daunorubicin, 36 mg/m2 of idarubicin or 40 mg/m2 of mitoxantrone)

- Patients must be in morphologic complete response (CR), complete response with
incomplete hematologic recovery (CRi) or partial response (PR) by international
working group criteria post induction therapy (see Appendix A). Patients in PR who
have undergone only one course of intensive induction therapy will be eligible only if
one or more of the following criteria are met:

- Patient preference to forgo further intensive induction therapy in favor of low-
or intermediate-intensity therapy

- Patients are deemed unlikely to benefit from additional anthracycline-cytarabine
induction therapies for any of the following reasons:

- Therapy-related AML

- Prior myelodysplastic syndrome or myeloproliferative neoplasm

- The presence of cytogenetic or molecular genetic features place patient in
the Intermediate-I, Intermediate -II or Adverse genetic group as defined by
the European LeukemiaNet

- Patients who have experienced one or more CTCAE v4.0 grade 3-4 treatment-related
non-hematologic toxicity within 30 days of beginning the first course of
induction therapy.

- Patients must have recovered from all infectious and non-hematologic toxicities from
prior chemotherapy to ≤ CTCAE grade 1 or baseline prior to study enrollment.

- Adequate renal and hepatic functions as indicated by the following:

- Renal function assessed by calculated creatinine clearance (CrCl) must be >/=
60ml/min by Cockcroft-Gault formula (

- Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN)

- AST/ALT ≤ 2.5 x ULN

- Patients in CRi must have evidence of hematologic recovery after prior therapy to at
least:

- Absolute neutrophils ≥ 0.8 x 109/L

- Platelets ≥ 75 x 109/L

- Independent of red blood cell transfusions

- ECOG performance status 0-2

Exclusion Criteria:

- Prior treatment with lenalidomide

- Known hypersensitivity to thalidomide

- Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as
specified in the protocol.

- The diagnosis of AML-M3 (acute promyelocytic leukemia) characterized by translocations
involving the retinoic acid receptor-alpha (RAR-alpha) gene.

- Use of investigational agents within 2 weeks or any anticancer therapy within 2 weeks
before study entry; the patient must have recovered from all acute toxicities from any
previous therapy.

- 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 vaccine are eligible.

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

- Patients with a systemic fungal, bacterial, viral, or other infection not controlled
(defined as exhibiting ongoing signs/symptoms related to the infection and without
improvement, despite appropriate antibiotics or other treatment).

- Have currently active gastrointestinal disease, or prior surgery that may affect the
ability of the patient to absorb oral lenalidomide