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A Phase II Study of Repeat Intranodal Injections of Adenovirus-CD 154 (Ad-ISF35) in Patients With Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma

Phase 2
18 Years
Open (Enrolling)
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

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Trial Information

A Phase II Study of Repeat Intranodal Injections of Adenovirus-CD 154 (Ad-ISF35) in Patients With Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma

This is a phase II clinical trial in which study subjects 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

Because this is the first time that repeat administration of Ad-ISF35 will be performed via
intranodal injection, and in order to allow sufficient time to evaluate the safety and
toxicity of this procedure, we will treat subjects 1 thru 3 at one month intervals and with
inpatient admission for 24 hours observation. After subject three receives their second
ISF35 injection we will proceed with enrollment of cohorts of four patients per month at one
week intervals until study enrollment has been completed. These subjects will be treated as
outpatients and will be observed for 3 hours prior to discharge.

ISF35 has already been used in Phase I clinical trials. The trials demonstrated that ISF35
treatment is well-tolerated and patients did not experience any significant or unexpected
adverse events. Patients reported flu-like symptoms from ISF35, which disappeared within one
to three days.

ISF35 is an abbreviation for Immune Stimulatory Factor 35, an offspring of technology
discovered by Dr. Thomas J. Kipps, MD, PhD, Professor, Department of Medicine and Deputy
Director for Research,UCSD Moores Cancer Center.

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

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 ≥

- 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

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

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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine and monitor clinical and biological responses in patients treated with repeat intranodal injections of Ad-ISF35.

Outcome Time Frame:

2 years (evaluation will be approx. 4 months per patient)

Safety Issue:


Principal Investigator

Januario Castro, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Associate Clinical Professor in the Blood and Marrow Transplantation Division


United States: Food and Drug Administration

Study ID:

UCSD-101357 - prev 080497



Start Date:

January 2009

Completion Date:

Related Keywords:

  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Lymphoma



University of California, San Diego Moores Cancer CenterSan Diego, California  92093