Safety and Dose Study of GRN163L to Treat Patients With Chronic Lymphoproliferative Disease(CLD)

Imetelstat Sodium (GRN163L) is a telomerase template antagonist with in vitro and in vivo
activity in a variety of tumor model systems. Telomerase is an enzyme that is active
primarily in tumor cells and is crucial for the indefinite growth of tumor cells. Inhibition
of telomerase may result in antineoplastic effects. High telomerase levels and short
telomere lengths correlate with other markers of poor prognosis in patients with chronic
lymphoproliferative disease.

Inclusion Criteria:

- 18 years of age or older

- Male or female

- Chronic lymphoproliferative disease with related biology or similar clinical pattern
to B-Cell Leukemia (CLL)including: small lymphocytic lymphoma (SLL), T cell
prolymophocytic leukemia (T-PLL), B cell prolymphocytic leukemia (B-PLL), mantle cell
lymphoma or other non-Hodgkins lymphoma in leukemic phase (peripheral blood
circulating malignant cells present), Waldenstrom's macroglobulinemia

- Must have relapsed from or be refractory to prior therapeutic regimens

- Patients with CLL or SLL must have received at least one prior purine analogue-based
chemotherapy regimen (eg, fludarabine, pentostatin or cladribine)

- If previously treated with an anthracycline, anthracenedione, or trastuzumab, must
have left ventricular ejection fraction > 50%

- ECOG performance status 0-2

- Life expectancy 3 months or greater

Exclusion Criteria:

- Pregnant or lactating women

- Active 2nd malignancy or history of another malignancy within 2 years,
except:treated, non-melanoma skin cancer,treated breast or cervical carcinoma in
situ,or resected T1a or b prostate cancer

- Chemotherapeutic agents within 4 weeks prior to study

- High dose CTX with stem cell support within 6 months prior to study

- Signal transduction inhibitors,or monoclonal antibodies within 4 weeks prior to study

- Immunotherapy or biological response modifiers within 4 weeks prior to study

- Systemic hormonal therapy within 4 weeks prior to study

- Anticoagulant therapy, antiplatelet therapy within 2 weeks prior to study

- Radiotherapy within 4 weeks prior to study

- Active autoimmune disorder

- Central nervous system or leptomeningeal involvement

- Clinically significant cardiovascular disease

- Known HIV infection

- Serious/active infection

- Surgical procedure within 2 weeks