A Trial of GS-9219 in Chronic Lymphocytic Leukemia (CLL), Non-Hodgkin's Lymphoma (NHL) or Multiple Myeloma (MM)

Study Overview
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Brief Summary
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Multi-center, open-label, single-dose, dose-escalating Phase I/II study of GS 9219 in adult patients with relapsed or refractory CLL, NHL or MM. Patients will be enrolled into the study in sequential dose cohorts. Patients will be administered a single IV infusion of GS 9219 on Day 1 of a 21 day cycle and may receive a total of six treatment cycles based on toxicities and response. Patients who demonstrate disease progression will be discontinued from the study. Patients who, at the completion of six treatment cycles, tolerate treatment and show evidence of disease control (response or stabilization) will be eligible to continue receiving treatment at the same dose.

Detailed Description
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The primary objective of this study is as follows: To assess the safety, toxicity, and maximum tolerated dose (MTD) of GS 9219 administered via IV administration once every three weeks (21 days) for six treatment cycles, i.e. for a total of 18 weeks, in patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL), Non-Hodgkin's Lymphoma (NHL) or Multiple Myeloma (MM). The secondary objectives of this study are as follows: To determine the pharmacokinetic parameters of GS 9219 for this regimen and patient population. To assess the antitumor activity of GS 9219 based on Response Rate and Duration of Response. Progression-free Survival and Overall Survival will be assessed if applicable.

Official Title
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Multi-center, Open-label, Dose-escalating Phase I/II Trial of GS-9219 Administered Once Every Three Weeks Intravenously to Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin's Lymphoma or Multiple Myeloma

Conditions
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Non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia, Multiple Myeloma

Intervention / Treatment
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* Drug: GS-9219


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsed or refractory CLL, NHL or MM ECOG Performance Status of 0, 1, or 2 Adequate organ function (protocol defined) ECG without evidence of clinically significant ventricular arrhythmias Exclusion Criteria: AIDS-related lymphoma Subjects with NHL who present exclusively with non-measurable lesions Subjects with MM who have non-secretory and/or non-measurable disease Recent anticancer therapy (chemotherapy, radiotherapy, and/or biotherapy)within four weeks prior to starting treatment Evidence of pulmonary fibrosis Other concurrent malignancy Uncontrolled concurrent illness Receiving chronic, systemically administered steroids Known hypersensitivity to nucleoside analogues

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 |
| --- | --- |
| Experimental: GS-9219<br>Escalating doses of GS-9219 (5, 8, 11.5, 16, 22.5, 31.5, 44, and 61.5 mg/m^2) until determination of the maximum tolerated dose (MTD) | Drug: GS-9219<br>* GS-9219 Injection is a clear, and colorless to slightly yellow aqueous solution containing 4 mg/mL of GS 9219. GS 9219 will be administered via IV infusion over 30 minutes in 100 mL of normal saline solution, every 21 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of MTD | Toxicity will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE). The MTD will be the highest dose level immediately below the dose level where two or more of three to six patients experience a dose-limiting toxicity (DLT). | All visits | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of GS-9219 and its metabolites | Pharmacokinetics (Cmax, Tmax, Clast, Tlast, λz, t1/2, AUClast, AUCinf, and %AUCexp) measured by blood sampling | AAA) CLL/NHL: at Cycles 1, 3, and 6: MM: Cycles 1, 2, 3, 4, 5, and 6 | 
| Response rate | Response rate measured by: CLL: National Cancer Institute Working Group (NCIWG) criteria NHL - National Cancer Institute (NCI) criteria; Response Evaluation in MM - International Myeloma Working Group (IMWG) criteria. | CLL/NHL: at Cycles 1, 3, and 6: MM: Cycles 1, 2, 3, 4, 5, and 6 | 
| Duration of response | Duration of response measured by: CLL: National Cancer Institute Working Group (NCIWG) criteria NHL - National Cancer Institute (NCI) criteria; Response Evaluation in MM - International Myeloma Working Group (IMWG) criteria. | CLL/NHL: at Cycles 1, 3, and 6: MM: Cycles 1, 2, 3, 4, 5, and 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLL, Hematologic Malignancies, NHL, Chronic Lymphocytic Leukemia, Non-Hodgkin's Lymphoma, CLL and NHL, Multiple Myeloma, MM