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A Phase I Trial of Autologous CLL B Cells Transduced to Express Chimeric CD154 (ISF35)

Phase 1
18 Years
Not Enrolling
Chronic Lymphocytic Leukemia

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Trial Information

A Phase I Trial of Autologous CLL B Cells Transduced to Express Chimeric CD154 (ISF35)

Memgen's first TNF family derived product, ISF35, is a gene that encodes a recombinant
protein molecule that binds and activates human CD40+ B lymphocytes that are found on a vast
majority of malignant leukemias and lymphomas.

In this clinical trial, ISF35 will be introduced into the patients' CLL cells ex vivo using
a replication-defective adenovirus Ad5 encoding the ISF35 cDNA transgene. After this ex vivo
manipulation, the modified leukemia cells will be extensively washed and the amount of
remaining free virus is measured before the cells are reinfused into the patient. Following
ex vivo transduction, the CLL cells expressing ISF35 activate a therapeutic immune response
directed against the target leukemia cells.

This ascending-dose trial will be divided into three dosing cohorts to determine the
existence of a maximum tolerated dose.

Patients will be followed for 12 months after ISF35 administration or until initiation of
another treatment.

Inclusion Criteria:

1. Subjects must have a diagnosis of B cell CLL, measurable disease, and an

NCI-WG indication for treatment with one of the following:

- Massive (>6 cm below left costal margin) or progressive splenomegaly;

- Massive (>10 cm longest diameter) lymph nodes, nodal clusters, or progressive

- Progressive anemia;

- Progressive thrombocytopenia;

- Weight loss > 10% body weight over the preceding 6 month period;

- Fatigue attributable to CLL;

- Fever or night sweats without evidence of infection;

- Progressive lymphocytosis.

2. Subjects must be age 18 years or older.

3. Women of childbearing potential (not postmenopausal for at least one year or not
surgically incapable of bearing children) must agree not to become pregnant for the
duration of the study. Both men and women participants must agree to use
contraception for the duration of the study.

4. Subjects must have Zubrod performance status of ≤ 2 (Appendix B).

5. Subjects must have adequate hematologic, renal, hepatic, and coagulation function:

- Adequate hematologic function:

- Platelet count ≥ 50,000/μl; AND

- Hemoglobin ≥ 10 g/dl (may be supported by erythropoietin or transfusion).

- Adequate renal function:

- Serum creatinine ≤ 1.5 times upper limit of normal; OR

- Measured creatinine clearance ≥ 40 mL/min/1.73 m^2.

- Adequate hepatic function:

- Total bilirubin ≤ 2.5 times upper limit of normal; AND

- ALT ≤ 2.5 times upper limit of normal; AND

- Adequate coagulation tests:

- Prothrombin time international normalized ratio (INR) ≤ 2; AND

- Partial thromboplastin time ≤ 1.66 times upper limit of normal

6. Subjects must be able to give written informed consent.

Exclusion Criteria:

1. Presence of more than 55% prolymphocytes.

2. Chemotherapy (e.g., purine analogues, alkylating agents, or corticosteroids),
antibody therapy, immunotherapy, radiation therapy, or participation in any
investigational drug treatment within 4 weeks of enrollment into protocol or at any
time during the study.

3. Ongoing toxicity from prior anti-neoplastic therapy.

4. Prior gene therapy or allogeneic stem cell transplantation.

5. Untreated autoimmune hemolytic anemia or immune thrombocytopenia.

6. Active infection requiring parenteral antibiotics.

7. Known HIV/HBV/HCV seropositivity.

8. Uncompensated hypothyroidism (defined as TSH greater than 4x upper limit of normal
not treated with replacement hormone).

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:

Assess the toxicity, tolerability, and safety of 1x10^8, 3x10^8, and 1x10^9 autologous Ad-ISF35-transduced CLL B cells given as a single intravenous infusion in patients with CLL.

Outcome Time Frame:

Duration of the trial

Safety Issue:


Principal Investigator

William G. Wierda, M.D., Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

June 2006

Completion Date:

March 2008

Related Keywords:

  • Chronic Lymphocytic Leukemia
  • Chronic lymphocytic leukemia
  • CLL
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, B-Cell
  • Immune System Diseases
  • ISF35
  • Ad-ISF35
  • Immunotherapy
  • Immune therapy
  • Active immune therapy
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid



University of Texas M.D. Anderson Cancer Center Houston, Texas  77030