Study of Lenalidomide With Vorinostat in Pediatric Patients With High Grade or Progressive CNS Tumors

Inclusion Criteria:

* Must have histologically confirmed central nervous system malignancy for which standard curative measures do not exist or are not loner effective
* Must have measurable disease
* may not have received vorinostat and lenalidomide in combination
* At least 3 weeks since prior chemotherapy
* At least 6 weeks from last nitrosurea
* At least 6 weeks from autologous transplant
* At least 3 months from bone marrow donor transplant
* At least 3 weeks from focal radiation
* At least 6 weeks from craniospinal radiation
* Must have not received growth factors within 1 week of study entry
* Must be on a stable or decreasing dose of steroids for 1 week prior
* Must not be receiving any chemo, biologic, or radiation therapy
* Must not be receiving enzyme inducing anticonvulsants or valproic acid
* Must not be receiving pro-thrombotic agents
* Karnofsky or Lansky performance status ≥50%
* Life expectancy of greater than 8 weeks
* Patients must have normal organ and marrow function, including
* Absolute neutrophil count ≥1,000/mcL
* Platelets ≥100,000/mcL
* Pulse oximetry \>93%
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
* aspartate aminotransferase (AST)(SGOT)/Alanine transaminase (ALT)(SGPT) ≤2.5 × institutional upper limit of normal
* Creatinine within normal institutional limits OR
* Creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
* The effects of vorinostat and lenalidomide on the developing human fetus are unknown. For this reason and because agents used in this trial are known to be teratogenic, women of child-bearing potential must commit to complete abstinence or use TWO methods of birth control (one highly effective (i.e. intrauterine device (IUD), birth control pills, injections, implants, tubal ligation, partner's vasectomy), and one additional method (i.e. male condom, diaphragm, cervical cap) for the duration of study participation and at least 28 days after completion. Females of childbearing potential must agree to ongoing pregnancy testing and counseling every 28 days about pregnancy precautions. If a female has not had a menstrual period in the preceding 24 consecutive months or has had a hysterectomy, the two methods of birth control requirement does not apply. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must agree to use condoms for the duration of study participation, and 28 days after completion.

Exclusion Criteria:

* Patient has not recovered from acute toxic effects of all prior therapies
* Patients who are receiving any other investigational agents
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat or lenalidomide
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, dyspnea at rest, symptomatic congestive heart failure, history of thromboembolism unrelated to central line, patients with known predisposition syndrome for thromboembolism, patients receiving anticoagulation therapy, unstable angina pectoris, cardiac arrhythmia, patients receiving enzyme inducing anticonvulsants, patients receiving valproic acid, patients receiving antiplatelet agents (aspirin, anti-inflammatory drugs), or psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant women are excluded from this study due to the potential for teratogenic effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is being treated and not resumed until 28 days after completing therapy.
* HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with these agents. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.