Inclusion Criteria

- ELIGIBILITY CRITERIA:

Histological diagnosis:

- Histological confirmation of a high-grade malignant glioma is required. Histologic
diagnoses include, but are not limited to, anaplastic astrocytoma and glioblastoma
multiforme. Patients with DIPG are exempt from histologic verification if they have
typical MRI findings of DIPG (i.e. hypo- or isointense on T1-weighted imaging,
hyperintense on FLAIR or T2-weighted imaging, epicenter in the pons, greater than 50%
of pons involved) in the face of a typical clinical presentation.

- Inoperable tumor or residual disease after resection

Prior therapy:

-No prior chemotherapy or radiation therapy for HGG or DIPG is permitted. Prior
chemotherapy or radiation therapy for treatment of other malignancies is permitted.

Age:

-Patients must be less than 22 years of age at the time of diagnosis.

Able to swallow capsules whole

Performance Score:

- Patients should have a Karnofsky/Lansky score of greater than or equal to 60.
Patients who require special assistance due to tumor-related paralysis, but who are
out of bed during the day will be considered ambulatory for the purpose of
calculating the performance score. Patients must be able to communicate any symptoms.

Laboratory Evaluation:

- The following laboratory values must be assessed within seven (7) days prior to the
start of therapy. Laboratory tests should be repeated within 48 hours of beginning
therapy if there has been a significant clinical change.

- Patients must have adequate organ and marrow function as defined below:

- absolute neutrophil count greater than or equal to 1,000/mcL

- platelets greater than or equal to 100,000/mcL

- total bilirubin less than 1.5 times upper limit of normal

- AST(SGOT)/ALT(SGPT) less than or equal to 2.5 times institutional upper limit of
normal

- creatinine below age-adjusted maximum limits below

OR

- creatinine clearance greater than or equal to 60 mL/min/1.73 m(2)

- Age (Years) - Maximum Serum Creatinine (mg/dl):

- Less than or equal to 5 years; 0.8

- Age greater than 5, but less than or equal to 10 ; 1.0

- Age greater than 1, but less than or equal to 15 ; 1.2

- Less than 15 years of age; 1.5

Females only:

- urine or serum pregnancy test negative

- No overt renal, hepatic, cardiac or pulmonary disease.

Steroids:

- Newly diagnosed patients may need to be on steroids due to surgery or control of
neurologic symptoms. Patients on steroids postoperatively or for control of
tumor-related edema are eligible, but attempts to keep patients on the lowest dose
necessary to control symptoms should be made.

Patients of childbearing potential:

-Female Subjects:

--Definition of female of childbearing potential (FCBP)

This protocol defines a female of childbearing potential as a sexually mature woman who:
1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally
postmenopausal (amenorrhea following cancer therapy does not rule out childbearing
potential) for at least 24 consecutive months (i.e., has had menses at any time in the
preceding 24 consecutive months).

--Criteria for female children of childbearing potential (FCCBP)

This protocol defines FCCBP as females who have:

---Achieved menarche and/or breast development in Tanner stage 2 or greater

----Onset of fertility typically occurs within 3-12 months after menarche.

Menarche varies considerably from person to person, and thus no age cut off can be
attributed. One of the primary tools used to follow a girl's progress through puberty is
the Tanner staging system, which describes the pattern of development of the secondary sex
characteristics. Tanner stage 2 corresponds to the beginning of breast development, which
is the first visible sign of puberty in girls. Breast development is estrogen stimulated,
and since ovulation cannot occur without estrogen, Tanner stage 2 will be a reliable
marker for the definition of fertility.

---Has not undergone a hysterectomy or bilateral oophorectomy.

Note: Amenorrhea following cancer therapy does not rule out childbearing potential

--Criteria for female children not of childbearing potential (FCNCBP)

This protocol defines FCNCBP as females:

- Who have not yet experienced menarche or breast development in Tanner stage 2.

- Who have undergone a hysterectomy or bilateral oophorectomy.

Females of childbearing potential (FCBP) 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 starting Course 1 of lenalidomide. Further, they 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 starting 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. A FCBP is a sexually mature woman 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). All patients must be counseled by a trained counselor
every 28 days about pregnancy precautions and risks of fetal exposure.

-Male Subjects:

- Appropriate male subjects (i.e. those who have reached puberty and are sexually
active) will be counseled regarding birth control methods. They must agree to use a
latex condom during sexual contact with females of childbearing potential while
participating in the study and for at least 28 days following discontinuation from
the study even if he has undergone a successful vasectomy.

- Appropriate male patients will be given a reproductive risks handout and counseled by
a provider. For sexually active patients, the counseling session, consent and
counseling checklist will be documented monthly.

Informed consent:

All patients or their legal guardians (if the patient is less than18 years old) or durable
power of attorney (DPA) must sign a document of informed consent indicating their
understanding of the investigational nature and the risks of this study. When appropriate,
pediatric patients will be included in all discussions in order to obtain verbal assent.

Durable Power of Attorney:

Assignment of DPA to a family member or guardian should be offered to all patients 18
years of age.

Signed informed consent according to institutional guidelines must be obtained.

EXCLUSION CRITERIA:

Patients who have had prior chemotherapy for this tumor.

Patients with an HGG that was completed resected with good margins.

Patients with a body surface area (BSA) less than or equal to 0.4 m(2) are excluded
because the lowest dose of the medication is 5 mg in capsule form.

Patients with a known coagulation disorder are excluded. Patients with a first-degree
relative with a history of venous thrombosis before age 50 yrs or an arterial thrombosis
before age 40 yrs must have the following testing performed prior to enrollment to exclude
a heritable disorder. Patients with a suspected disorder will be excluded due to the
potential increased risk of thrombosis.

- PT, PTT, Thrombin time, Fibrinogen

- Antithrombin

- Protein C, Protein S

- Factor V Leiden

- Prothrombin G20210A gene analysis

- Fasting serum homocysteine

- Lupus anticoagulant assays

- Anticardiolipin level

- Fasting serum homocysteine

- Anticardiolipin level

- LDL, HDL, triglycerides

Patients who have had a thromboembolic event that is not line-related are excluded.

Patients with any significant medical illnesses that, in the investigator's opinion,
cannot be adequately controlled with appropriate therapy, would compromise a patient's
ability to tolerate this therapy or result in inability to assess toxicity. This includes,
but is not limited to uncontrolled intercurrent illness including ongoing or active
infection, cardiac disease, renal impairment or psychiatric illness/social situations that
would limit compliance with study requirements.

Patients with a history of Toxic Epidermal Necrolysis (TEN) or Stevens-Johnson syndrome
are excluded as this has occurred in patients receiving lenalidomide.

Patients receiving any other investigational agents.

History of allergic reactions attributed to compounds of similar chemical or biologic
composition to lenalidomide (i.e. thalidomide).

Patients with known hypersensitivity to anhydrous lactose, microcrystalline cellulose,
croscarmellose sodium, and magnesium stearate.

Pregnant or breast feeding females:

Pregnant women are excluded from this study because lenalidomide is in a class with the
potential for teratogenic or abortifacient effects. Because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the mother
with lenalidomide, breastfeeding should be discontinued if the mother is treated with
lenalidomide.

Known HIV-positive patients on combination antiretroviral therapy are ineligible because
of the potential for pharmacokinetic interactions with lenalidomide. In addition, these
patients are at increased risk of lethal infections when treated with marrow-suppressive
therapy.

Patients identified as needing spinal radiation at diagnosis (e.g. spinal metastasis or
malignant cells identified on CSF cytology) are excluded due to the increased risk of
myelosuppression.