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

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and maximum tolerated dose of GRN163L in treating patients with refractory or relapsed chronic lymphoproliferative disease.

Detailed Description
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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.

Official Title
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A Phase I, Sequential Cohort, Dose Escalation Trial to Determine the Safety, Tolerability, and Maximum Tolerated Dose of GRN163L in Patients With Chronic Lymphoproliferative Disease

Conditions
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Chronic Lymphoproliferative Diseases

Intervention / Treatment
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* Drug: GRN163L


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: open label<br>Sequential dose cohort, open label, escalation trial evaluating one infusion duration of 2 hours | Drug: GRN163L<br>* Weekly intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety, tolerability, dose-limiting toxicities (DLT), and maximum tolerated dose (MTD) or recommended phase II dose of GRN163L in patients with relapsed or refractory chronic lymphoproliferative disease |  | First 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK and PD |  | Measured in the first 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Telomerase Inhibition, Chronic lymphocytic leukemia, T-cell prolymphocytic leukemia, Chronic lymphoproliferative diseases, Telomerase