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.

Exclusion Criteria:

1. Pregnant or nursing women
2. Treatment with chemotherapy or monoclonal antibody within 28 days prior to entering the study.
3. Treatment with chemotherapy or monoclonal antibody during the time of participation in this trial.
4. Grade 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
5. Severe or debilitating pulmonary disease (dyspnea at rest, significant shortness of breath, COPD).
6. Participation in any investigational drug study within 28 days prior to ISF35 administration. (Patient must have recovered from all acute effects of previously administered investigational agents).
7. Evidence of aggressive or highly aggressive lymphoma or Richter's transformation based on WHO/REAL classification criteria\[1\]
8. Any T cell lymphoma.
9. History of malignancy other than NHL or SLL/CLL or within five years of registration, except patients with adequately treated basal, squamous cell carcinoma or localized cervical cancer.
10. Active symptomatic fungal, bacterial and/or viral infection including active HIV or viral (A, B or C) hepatitis.
11. Any illness or condition that in the opinion of the Investigator may affect safety of treatment or evaluation of any the study's endpoints.