Low-Dose or High-Dose Lenalidomide in Treating Younger Patients With Recurrent, Refractory, or Progressive Pilocytic Astrocytoma or Optic Pathway Glioma
Condition: Neurofibromatosis Type 1; Recurrent Childhood Pilocytic Astrocytoma; Recurrent Childhood Visual Pathway Glioma
MeSH terms: Glioma; Astrocytoma; Neurofibromatoses; Neurofibromatosis 1; Recurrence
Intervention: Lenalidomide; Pharmacological Study
Intervention description: Given PO; Correlative studies
Intervention MeSH terms: Lenalidomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 75.0
Sex: All
Maximum age: 21 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well low-dose lenalidomide works compared with
      high-dose lenalidomide in treating younger patients with juvenile pilocytic astrocytomas or
      optic nerve pathway gliomas that have come back (recurrent), have not responded to treatment
      (refractory), or are growing, spreading, or getting worse (progressive). Lenalidomide is
      classified as an immunomodulatory drug as it boosts the immune system. It has other potential
      anti-tumor effects, for example, it may stop the growth of tumor cells by blocking blood flow
      to the tumor. It is not yet known whether low-dose lenalidomide is more or less effective
      than high-dose lenalidomide in treating patients with juvenile pilocytic astrocytomas or
      optic nerve pathway gliomas.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a body surface area (BSA) >= 0.4 m^2 at the time of study
             enrollment

          -  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 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

          -  Patients must have been treated with at least one prior treatment regimen that
             included carboplatin; patients who have received prior radiation therapy for this
             tumor are eligible

          -  Patients must have recovered (to Common Toxicity Criteria [CTC] version [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

               -  Myelosuppressive chemotherapy: must not have received within 3 weeks of entry
                  onto this study (6 weeks if prior nitrosourea or mitomycin-C)

               -  Biologic (anti-neoplastic agent): 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

               -  Immunotherapy: at least 42 days after the completion of any type of
                  immunotherapy, e.g. tumor vaccines

               -  Monoclonal antibodies: at least 3 half-lives of the antibody after the last dose
                  of a monoclonal antibody

               -  Radiation therapy (RT): patients must have had their last fraction of
                  craniospinal 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 thalidomide are eligible if all acute
                       thalidomide-related toxicity has resolved

                    -  Patients must not have received lenalidomide previously

          -  Growth factor(s): must not have received within 2 weeks of entry onto this study

          -  Steroids: patients who are receiving corticosteroids must be on a stable or decreasing
             dose for at least 1 week prior to baseline MRI

          -  Peripheral absolute neutrophil count (ANC) >= 1,000/uL

          -  Platelet count >= 100,000/uL (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/m^2
             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 x upper limit of normal (ULN) for age

          -  Serum glutamate 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

          -  All patients and/or their parents or legal guardians must sign a written informed
             consent

          -  All institutional, Food and Drug Administration (FDA), and National Cancer Institute
             (NCI) requirements for human studies must be met

        Exclusion Criteria:

          -  Female patients who are pregnant are not eligible

          -  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 (4 weeks) 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 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 every 28 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