Study of Lenalidomide With Vorinostat in Pediatric Patients With High Grade or Progressive CNS Tumors
Condition: Central Nervous System Tumors
MeSH terms: Nervous System Neoplasms; Central Nervous System Neoplasms
Intervention: 25 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®); 50 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®); 100 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®); 150 mg/m2 Lenalidomide (Revlimid®) and 180 mg/m2 Vorinostat (Zolinza®); 150 mg/m2 Lenalidomide (Revlimid®) and 230 mg/m2 Vorinostat (Zolinza®)
Intervention description: Drug: Lenalidomide 25 mg/m2 days 1-21 of a 28 days cycle Drug: Vorinostat 180 mg/m2 days 1-7 and 15-21 of a 28 day cycle; Drug: Lenalidomide 50 mg/m2 days 1-21 of a 28 days cycle Drug: Vorinostat 180 mg/m2 days 1-7 and 15-21 of a 28 day cycle; Drug: Lenalidomide 100 mg/m2 days 1-21 of a 28 days cycle Drug: Vorinostat 180 mg/m2 days 1-7 and 15-21 of a 28 day cycle; Drug: Lenalidomide 150 mg/m2 days 1-21 of a 28 days cycle Drug: Vorinostat 180 mg/m2 days 1-7 and 15-21 of a 28 day cycle; Drug: Lenalidomide 150 mg/m2 days 1-21 of a 28 days cycle Drug: Vorinostat 230 mg/m2 days 1-7 and 15-21 of a 28 day cycle
Intervention MeSH terms: Lenalidomide; Vorinostat
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 1 Year
Maximum age: 21 Years
Healthy volunteers: No

Summary:

      Independently, both lenalidomide and vorinostat have shown promising activity in pediatric
      central nervous system (CNS) tumors. These are both agents that are not typically part of
      first-line studies, although both agents are of serious interest and are currently in
      clinical trials for further investigation. This study is to evaluate the combination of
      lenalidomide and vorinostat in high grade or progressive central nervous system tumors in
      children.
    

Eligibility criteria:

        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.