Study of Repeat Intranodal Injection of Memgen's Cancer Vaccine, Ad-ISF35, in Subjects With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
Condition: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: ISF35
Intervention description: Subjects participating in this study will be treated with multiple doses of Ad-ISF35 given via intranodal injection using a fixed dose of 3.3 x 10^10 ISF35 viral particles. Intranodal injections will be administered every 2-4 weeks up to six total injections.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a Phase II, open label, fixed dose, repeat injection, single institution study.
      Eligible subjects will receive up to six doses of Ad-ISF35 injected directly into a selected
      lymph node under ultrasound guidance. The primary goal is to determine and monitor clinical
      and biological responses in patients treated with repeat intranodal injections of Ad-ISF35.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosis of B-cell CLL/SLL 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 CLL/SLL 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 CLL/SLL

          4. Indication for treatment as defined by the NCI Working Group Guidelines:

               -  Massive (> 6 cm below the left costal margin) or progressive splenomegaly OR

               -  Massive lymph nodes or nodal clusters (> 10 cm in longest diameter) OR
                  *Progressive lymphadenopathy OR

               -  Grade 2 or 3 fatigue OR

               -  Fever ≥ 100.5 degrees 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.

          5. Males and females 18 years of age and older

          6. Laboratory parameters as specified below:

               -  Hematologic: Hemoglobin ≥ 10 g/dL (may be post-transfusion); platelet count ≥
                  50x10^3/mm^3

               -  Hepatic: Total Bilirubin < 2 x ULN, and ALT and AST < 2 x ULN

               -  Renal: Creatinine ≤ 2 x ULN

          7. ECOG Performance Status ≤ 2

          8. Anticipated survival of at least 3 months

          9. For men and women of child-producing potential, use of effective barrier contraceptive
             methods during the study and for one month following treatment.

         10. 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.

         11. Negative test results for current/active infection with HIV-1, HIV-2, HTLV-1, HTLV-2,
             CMV, hepatitis A, B, C within 30 days of registration. (Antibody, antigen and nucleic
             acid tests acceptable, depending on institutional standards.).

         12. Subjects must give written informed consent to participate in this trial.

         13. Subjects must have received treatment for CLL with chemotherapy agents or antibodies
             OR if subjects are previously untreated they must state in the consent form that they
             are refusing to be treated with chemotherapy or antibodies.

        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. History of malignancy other than CLL within five years of registration, except
             patients with adequately treated basal, squamous cell carcinoma or localized cervical
             cancer.

          8. Active symptomatic fungal, bacterial and/or viral infection including active HIV or
             viral (A, B or C) hepatitis.

          9. Any illness or condition that in the opinion of the Investigator may affect safety of
             treatment or evaluation of any the study's endpoints.