Intervention: Isosorbide
Trial phase: Phase 2
SMILES: [H][C@]12OC[C@@]([H])(O)[C@@]1([H])OC[C@]2([H])O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 56
Group description: Patients receive oral R-(-)-gossypol once daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Patients undergo tumor tissue and blood sample collection at baseline and periodically during study for biomarker correlative studies. Archived tumor tissue samples, if available, are analyzed for Bcl-2 family protein expression (e.g., Bcl-2, Bcl-xL, MCl-1, Bax, Bak, and BH3 domain for BH3 members only) and MGMT gene methylation status. Blood samples are analyzed for apoptotic protein levels (Bcl-2) by enzyme-linked immunosorbent assay.

R-(-)-gossypol acetic acid: Given PO

laboratory biomarker analysis: Correlative studies
Eligibility criteria:
Inclusion Criteria:

Patients must have histologically confirmed supratentorial glioblastoma multiforme which is progressive or recurrent after radiation therapy ± chemotherapy; patients with previously low grade glioma who progressed after radiotherapy ± chemotherapy and are biopsied and found to have glioblastoma multiforme are eligible
Patients must have tumor tissue form completed and signed by a pathologist
Patients must have measurable contrast enhancing progressive or recurrent glioblastoma multiforme by MRI or CT imaging (Within 14 days before starting treatment)
Patients must have recovered from toxicity of prior therapy; an interval of at least 3 months must have elapsed since the completion of the most recent course of radiation therapy, while at least 3 weeks must have elapsed since the completion of a non-nitrosourea containing chemotherapy regimen, and at least 6 weeks since the completion of a nitrosourea containing chemotherapy regimen; NOTE: For non-cytotoxic, FDA approved agents (i.e. celebrex, thalidomide, etc.) therapy could be started 2 weeks after discontinuing this agent provided the patient has fully recovered from all toxicity associated with the agent; for investigational, non-cytotoxic agents a minimum of 3 weeks must have elapsed before the patient will be eligible for this study
Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
Absolute neutrophil count >= 1500/mm^3
Platelets >= 100,000/mm^3
Creatinine =< 1.5mg/dl
Total Bilirubin =< 1.5mg/dl
Transaminases =< 2.5 times above the upper limits of the institutional norm
Patients must be able to provide written informed consent
Women of childbearing potential must have a negative serum pregnancy test; the effects of AT-101 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because Bcl-2 inhibitors have the potential to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and for at least one month following the last dose of AT-101; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Patients must have a Mini Mental State Exam score >= 15

Exclusion Criteria:

Patients with serious concurrent infection or medical illness which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety; (Examples of medical illnesses are [but not limited to] the following: uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements)
Patients who are pregnant or breast-feeding
Patients who have received more than two prior treatments
Patients who have been previously treated with gossypol, or have allergies to gossypol
Patients receiving concurrent therapy for their tumor (i.e. chemotherapeutics or investigational agents); concurrent steroid use is allowed
Patients with a concurrent malignancy are ineligible unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin; patients with a prior malignancy are ineligible unless they have been free of disease for >= five years
Patients with ≥ Grade 2 sensory neuropathy based on the NCI CTCAE
Patients who are taking iron supplements
Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow pills are excluded
Patients cannot be receiving cytochrome P450-inducing anticonvulsants (EIAEDs; e.g., phenytoin, carbamazepine, phenobarbital, primidone, oxcarbazepine)
Patients with malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel are excluded; subjects with ulcerative colitis, inflammatory bowel disease, or a partial or complete small bowel obstruction are also excluded
Eligibility of patients receiving any other medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of AT-101 will be determined following review of their case by the Principal Investigator
Patients with symptomatic hypercalcemia that is > Grade 2 (according to CTCAE)
Requirement for routine use of hematopoietic growth factors (including granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, or interleukin-11) or platelet transfusions to maintain absolute neutrophil counts or platelets counts above the required thresholds for study entry
HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AT-101; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated