Study of Repeat Intranodal Injections of Ad-ISF35

Inclusion Criteria

• •SLL / CLL PATIENTS
• •1. Diagnosis of B-cell SLL/ CLL including
• •* Lymphocytosis of monoclonal B-cells co-expressing ≥ one B-cell marker (CD19, CD20, or CD23) and CD5 in peripheral blood or lymph node AND
• •* Bone marrow with ≥ 30% mononuclear cells having the SLL / CLL phenotype.
• •2. Presence of at least ONE single accessible AND palpable lymph node in the cervical, supraclavicular, axillary, or inguinal regions. The size of the lymph nodes must be larger than 2x2 cm in the horizontal and perpendicular axes.
• •3. Intermediate or High risk, poor prognosis SLL / CLL
• •4. Indication for treatment as defined by the NCI Working Group Guidelines:
• •* Massive (i.e. \> 6 cm below the left costal margin) or progressive splenomegaly OR
• •* Massive lymph nodes or nodal clusters (i.e. \> 10 cm in longest diameter), or progressive lymphadenopathy OR
• •* Grade 2 or 3 fatigue OR
• •* Fever ≥ 100.5˚F or night sweats for greater than 2 weeks without documented infection OR
• •* Presence of weight loss ≥ 10% over the preceding 6 months OR
• •* Progressive lymphocytosis with an increase of ≥ 50% over a 2-month period or an anticipated doubling time of less than 6 months.
• •* Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and / or thrombocytopenia.
• •* Autoimmune anemia and / or thrombocytopenia poorly responsive to corticosteroid therapy.
• •NHL PATIENTS
• •5. Non-Hodgkin's Lymphoma patients that have received at least one prior treatment (Antibodies and / or chemotherapy). Patients must have one of the following subtypes according to the WHO/REAL Classification\[1\]: follicular lymphoma, diffuse large cell lymphoma, mantle cell lymphoma and small lymphocytic lymphoma / chronic lymphocytic lymphoma.
• •6. Stage III or IV disease at any time in the past (Ann Arbor Staging System for Non-Hodgkin's Lymphomas).
• •7. Presence of at least ONE single accessible AND palpable lymph node in the cervical, supraclavicular, axillary, or inguinal regions. The size of the lymph nodes must be larger than 2x2 cm in the horizontal and perpendicular axes.
• •ALL PATIENTS
• •8. Males and females 18 years of age and older
• •9. Laboratory parameters as specified below:
• •* Hematologic: Hemoglobin ≥ 10 g/dL (may be post-transfusion); platelet count ≥ 50 x103/mm3
• •* Hepatic: Total Bilirubin \< 2 X ULN, and ALT and AST \< 2 x ULN
• •* Renal: Creatinine ≤ 2 X ULN
• •10. ECOG Performance Status ≤ 2
• •11. Anticipated survival of at least 3 months
• •12. For men and women of child-producing potential, use of effective barrier contraceptive methods during the study and for one month following treatment.
• •13. Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and return for the required assessments.
• •14. Negative test results for current/active infection with HIV-1, HIV-2, HTV-1, HTLV-2, hepatitis A, B, C within 30 days of registration. (Antibody, antigen and nucleic acid tests acceptable, depending on institutional standards.).
• •15. Subjects must give written informed consent to participate in this trial.