Study to Evaluate Eflornithine + Lomustine vs Lomustine in Recurrent Anaplastic Astrocytoma (AA) Patients

This study will consist of 4 study periods of up to 50 months in total, consisting of:

Screening Period - A maximum screening duration of 4 weeks.

Treatment Period - Treatment Arm A up to 24 months; Treatment Arm B up to 12 months.

End of Treatment Visit - A minimum of 4 weeks post last treatment for both arms.

Follow-Up Period - Up to 24 months.

A total of approximately 340 patients will be randomized in a 1:1 ratio to receive either
eflornithine + lomustine or lomustine alone.

Inclusion Criteria:

Patients must meet all of the following inclusion criteria to be eligible for participation
in this study:

- Surgical or biopsy-proven diagnosis of WHO grade 3 AA.

- First AA tumor progression or recurrence ≤ 6 months prior to randomization based on
MRI using T2 hyperintesity, gadolinium (Gd)-contrast enhancement, or both. To avoid
enrollment of patients with glioblastoma, patients with Gd-contrast enhancing tumors
will be eligible if there is no necrosis seen on MRI and any of the following criteria
is true:

1. Gd-contrast lesion margins are not clearly defined,

2. Gd-contrast lesions are only measurable in one dimension,

3. Gd-contrast lesion has two perpendicular diameters less than 10 mm,

4. Gd-contrast lesion has two perpendicular diameters greater than 10 mm but less
than 20 mm and lesion does not demonstrate central necrosis,

5. Recent histopathological confirmation of WHO grade 3 AA

- Received EBRT and temozolomide chemotherapy prior to first tumor progression or
recurrence of WHO Grade 3 AA.

- Completion of EBRT ≥ 6 months prior to randomization.

- A patient whose AA tumor has progressed or recurred and has had another surgical
resection prior to randomization will be eligible if a) pathology review confirms AA,
and b) post-surgical MRI demonstrates measurable tumor on T2 FLAIR.

- Karnofsky Performance Status (KPS) score of ≥ 70.

Exclusion Criteria:

Patients who meet any of the following exclusion criteria are not eligible for study
participation:

- MRI defining progression is consistent with a diagnosis of glioblastoma or radiation
necrosis.

- Patients who are considered to be refractory to EBRT and temozolomide but who have not
progressed.

- Prior systemic therapy for recurrence of AA.

- Presence of extracranial or leptomeningeal disease.

- Prior lomustine use.

- Any other clinical condition or prior therapy that, in the opinion of the
Investigator, would make the patient unsuitable for the study.

- Pregnant or breastfeeding.