| Inclusion Criteria: | 1) Age >/= 18 years
2) Subjects with relapsed or refractory CLL, NHL or MM. Patients are considered relapsed or refractory when showing evidence of disease progression after having either: at least two prior chemotherapy regimens, i.e., primary treatment and at least one salvage therapy. The therapies must include a single or multiple chemotherapy drugs with well documented activity in NHL, CLL, or MM to ensure that only patients with no know effective alternative therapy are included.
3) (Cont.) Antibodies such as rituximab, when given alone will not count as a primary or salvage therapy. Antibody therapy, given in combination with a single drug or a combination chemotherapy regimen will be considered one prior chemotherapy. Subjects with prior stem cell transplant (autologous or allogeneic) are eligible. Pre-induction chemotherapy with auto or allo transplant will be considered one prior chemotherapy, or a single high dose chemotherapy regimen that require bone marrow or stem cell support and in the opinion of the investigator no longer have potentially curable disease.
4) (continued) Subjects with CLL will be staged according to the Rai staging criteria. All patients in the Rai high-risk groups (i.e., Rai stages 3 and 4 based on the original five-stage system) are eligible. Intermediate risk patients (i.e., Rai stages 1 and 2 based on the original five-stage system) with one or more signs of active disease (such as progressive lymphocytosis, lymphadenopathy, splenomegaly, weight loss > 10% within six months, extreme fatigue, fever and/or night sweats without evidence of infection) are also eligible.
5) (continued) Subjects with NHL will be staged according to the Ann Arbor classification and must present with bi-dimensionally measurable disease either on physical examination or on imaging studies. Any tumor mass measurable in two dimensions and >/= 2 cm in its longest transverse diameter is acceptable (or >/= 1.5 cm in its longest transverse diameter if 0.5 cm slices are used as in spiral CT scans).
6) Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
7) Subjects must demonstrate adequate organ function during the Screening Period and at the Cycle 1 Pre-Dose assessment as defined below: Dose Escalation (Part A Only): Hematology: Absolute neutrophil count (ANC) >/= 1,500 cells/mm3, Platelets >/= 100,000/mm3, and Hemoglobin >/= 8.5 g/dL; Liver Function: Total serum bilirubin within normal range, Aspartate transaminase (AST) </= 3 times ULN, and Alanine transaminase (ALT) </= 3 times ULN; Renal Function: Serum creatinine </= 1.5 mg/dL
8) Electrocardiogram (ECG) without evidence of clinically significant ventricular arrhythmias, conduction abnormalities, or active ischemia as determined by the Investigator. Pulmonary function test, chest x-ray or CT scan of the chest if not performed within 4 weeks before dosing of study drug (GS-9219). The pulmonary function testing and chest x-ray are done to record lung conditions before study dosing, in case respiratory symptoms are developed during the study.
9) Males and females of childbearing potential (less than 1 year postmenopausal or no history of hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) must agree to utilize a highly effective method of contraception throughout the study period and for 30 days following discontinuation of study drug. A highly effective method of birth control is defined as a method that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence, or a vasectomized partner.
10) Ability to understand and willingness to sign a written informed consent document.
11) Subjects with MM will be staged according to the International Staging System (ISS) (Appendix 10 of protocol). All patients with Stage II or III disease are eligible. Subjects must have secretory and measurable disease [measurable defined as one or more of the following: serum M-protein >/= 1 g/dL by serum protein electrophoresis, urine M-protein >/= to 200 mg/24 hours, serum free light chain (FLC) measurement >/= 10 mg/dL provided serum FLC ratio is abnormal.]
12) MTD Expanded Cohort (Part B Only): Hematology - Absolute neutrophil count (ANC) - 1,000 cells/mm3; Platelets - 50,000/mm3, and Hemoglobin - 8.0 g/dL; Liver Function - total serum bilirubin within normal range; Aspartate transaminase (AST) - 2.5 times ULN; Alanine transaminase (ALT) - 2.5 times ULN; Renal function - serum creatinine 3.0 mg/dL. |