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

Sponsor

Geron Corporation (Industry)

Overall Status

Completed

CT.gov ID

NCT00124189

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphoproliferative Diseases	Drug: GRN163L	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

48 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2005

Actual Primary Completion Date :

Mar 1, 2013

Actual Study Completion Date :

Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Other: open label Sequential dose cohort, open label, escalation trial evaluating one infusion duration of 2 hours	Drug: GRN163L Weekly intravenous infusion

Arm

Intervention/Treatment

Other: open label

Sequential dose cohort, open label, escalation trial evaluating one infusion duration of 2 hours

Drug: GRN163L

Weekly intravenous infusion

Outcome Measures

Primary Outcome Measures

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

PK and PD [Measured in the first 6 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rocky Mountain Cancer Center	Denver	Colorado	United States	80218
2	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
3	Roswell Park Cancer Center	Buffalo	New York	United States	14263
4	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11040
5	Weill Medical College of Cornell University	New York	New York	United States	10021
6	The Ohio State University James Cancer Hospital	Columbus	Ohio	United States	43210
7	UT Southwestern	Dallas	Texas	United States	75390
8	University of Texas Health Science Center	San Antonio	Texas	United States	78229