A Phase II Randomized Trial of Lenalidomide (NSC # 703813, IND # 70116) in Pediatric Patients With Recurrent, Refractory or Progressive Juvenile Pilocytic Astrocytomas and Optic Pathway Gliomas

Inclusion Criteria:

- Patients must have a pilocytic astrocytoma or optic pathway glioma that has relapsed,
progressed, or become refractory to conventional therapy; patients with
neurofibromatosis (NF-1) are eligible

- Patients must have histologic verification of malignancy; histologic confirmation for
patients with optic pathway gliomas will not be required

- Patients must have measurable residual disease, defined as tumor that is measurable
in two perpendicular diameters on magnetic resonance imaging (MRI); for a lesion to
be considered measurable, it must be at least twice the slice thickness on MRI (i.e.,
visible on more than one slice)

- To document the degree of residual tumor, the following must be obtained:

- All patients must have a brain MRI with and without contrast (gadolinium) within
1 week prior to study enrollment; for patients on steroids, baseline MRI scans
must be performed after at least 1 week at a stable or decreasing dose of
steroids

- All patients with a history of spinal or leptomeningeal disease, and those
patients with symptoms suspicious of spinal disease, must have a spine MRI with
and without contrast (gadolinium) performed within 2 weeks prior to study
enrollment

- Patients must have been treated with two or fewer anti-cancer regimens, including
chemotherapy, biologic agents, immunotherapy, vaccines, monoclonal antibodies, or
radiation therapy

- At least one prior treatment regimen must have included carboplatin

- Patients who have received prior radiation therapy for this tumor are eligible

- Patients must have a body surface area (BSA) ≥ 0.4 m² at the time of study enrollment

- Patients must have a Lansky or Karnofsky performance status score of ≥ 60%; use
Karnofsky for patients> 16 years of age and Lansky for patients ≤ 16 years of age

- Peripheral absolute neutrophil count (ANC) ≥ 1,000/μL

- Platelet count ≥ 100,000/μL (transfusion independent)

- Hemoglobin ≥ 8.0 g/dL (may receive red blood cell [RBC] transfusions)

- Creatinine clearance or radioisotope glomerular filtration rate(GFR) ≥ 70 mL/min OR a
serum creatinine based on age/gender as follows:

- 0.4 mg/dL (1 month to < 6 months of age)

- 0.5 mg/dL (6 months to < 1 year of age)

- 0.6 mg/dL (1 to < 2 years of age)

- 0.8 mg/dL (2 to < 6 years of age)

- 1.0 mg/dL (6 to 10 years of age)

- 1.2 mg/dL (10 to < 13 years of age)

- 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)

- 1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age

- Serum glutamic pyruvate transaminase(SGPT) (alanine aminotransferase [ALT]) ≤ 110
U/L; for the purpose of this study, the ULN for SGPT is 45 U/L

- Serum albumin ≥ 2 g/dL

- No evidence of dyspnea at rest and a pulse oximetry > 94% if there is clinical
indication for determination

- Patients must be able to swallow intact capsules

- Not pregnant or breastfeeding

- Lactating females are not eligible unless they have agreed not to breastfeed
their infants while receiving protocol therapy and for 28 days after the last
dose of lenalidomide

- Female patients of childbearing potential are not eligible unless they commit to
complete abstinence or have been on 2 methods of birth control, including 1 highly
effective method and 1 additional method at the same time (unless committing to
complete abstinence of heterosexual intercourse), at least 28 days (4weeks) prior to
study enrollment; sexually active females must also agree to remain on 2 methods of
birth control during treatment (including during dose interruptions) and continuing
for at least 28 days after the completion of protocol therapy; examples of methods of
contraception are as follows:

- Highly effective methods (must use at least 1):

- Intrauterine device (IUD)

- Hormonal (prescription birth control pills, injections, implants)

- Tubal ligation

- Partner's vasectomy

- Additional effective methods:

- Male condom

- Diaphragm

- Cervical cap

- The two methods of birth control requirement applies to all sexually active
females unless they have not had a menstrual period in the preceding 24
consecutive months or have undergone a hysterectomy or bilateral oophorectomy

- Female patients of childbearing potential (including those who commit to complete
abstinence) are not eligible unless they agree to ongoing pregnancy testing and
counseling every28 days about pregnancy precautions and risks of fetal exposure

- Male patients of child-fathering potential are not eligible unless they have agreed
to use latex condoms during intercourse with a woman of childbearing potential while
receiving treatment and for 28 days thereafter

- Patients with a history of thromboembolism unrelated to a central line or patients
with a known predisposition syndrome for thromboembolism are not eligible

- Patients who have an uncontrolled or untreated infection are not eligible

- Patients with known overt cardiac disease including, but not limited to, a history of
myocardial infarction, severe or unstable angina, clinically significant peripheral
vascular disease, Grade 2 or greater heart failure, or serious and inadequately
controlled cardiac arrhythmia are not eligible

- Patients with a significant systemic illness that is not well-controlled, in the
opinion of the treating physician, are not eligible

- See Disease Characteristics

- Patients must have recovered (to common terminology criteria [CTC] v.4.0 ≤ Grade 1
unless indicated below) from the acute toxic effects of all prior chemotherapy,
immunotherapy, or radiotherapy prior to entering this study, with the exception of
alopecia, weight changes, and Grade I or II lymphopenia

- Must not have received myelosuppressive chemotherapy within 3 weeks of entry
onto this study(6 weeks if prior nitrosourea or mitomycin C)

- At least 7 days after the last dose of a biologic agent; for agents that have
known adverse events occurring beyond 7 days after administration, this period
must be extended beyond the time during which adverse events are known to occur

- At least 42 days after the completion of any type of immunotherapy, e.g., tumor
vaccines

- At least 3 half-lives of the antibody after the last dose of a monoclonal
antibody

- Patients must have had their last fraction of craniospinal radiotherapy (RT)≥ 6
months prior to study entry and their last fraction of focal RT ≥ 4 weeks prior
to study entry; if the lesion used for on-study criteria is in the radiation
field, there must be evidence of tumor progression after radiation therapy was
completed

- Study-specific limitations on prior therapy:

- Patients who have received prior thalidomide are eligible if all acute
thalidomide-related toxicity has resolved

- Patients must not have received lenalidomide previously

- Must not have received growth factor(s) within 2 weeks of entry onto this study

- Patients who are receiving corticosteroids must be on a stable or decreasing dose for
at least 1 week prior to baseline MRI

- Concurrent cancer therapy, including chemotherapy, radiation therapy, immunotherapy,
or biologic therapy, may NOT be administered to patients while on this study