Know Cancer

forgot password

A Phase 1B Extension Trial to Allow Repeat Dosing of Autologous CLL B Cells Transduced to Express Chimeric CD154 (ISF35) in Subjects Previously Treated in MDACC Protocol 2004-0914

Phase 1
18 Years
Not Enrolling
Chronic Lymphocytic Leukemia

Thank you

Trial Information

A Phase 1B Extension Trial to Allow Repeat Dosing of Autologous CLL B Cells Transduced to Express Chimeric CD154 (ISF35) in Subjects Previously Treated in MDACC Protocol 2004-0914

In a previous Phase I clinical trial at M.D. Anderson, patients with CLL received an
intravenous infusion of autologous leukemia cells transduced ex vivo with an adenovirus
encoding the wild-type murine CD154. This treatment was well tolerated and without
dose-limiting toxicity. Patients each experienced acute reductions in the leukemia-cell
blood count and in the size of enlarged lymph nodes and spleen.

The infusion induced changes in circulating bystander, non-infected CLL cells and both acute
and long-term clinical responses. The changes in bystander CLL cells were similar to those
observed in CLL cells following ligation of CD40, which included enhanced or de novo
expression of CD54, CD80, and CD86, allowing the modified CLL cells to function more
effectively in presenting antigens to autologous T cells. Following CD40 ligation, CLL
cells are induced to express CD95 and DR5 and to undergo changes in expression of pro- and
anti-apoptotic proteins, ultimately favoring apoptosis in the CLL cells.

To build upon these results, an extension to this trial will be completed in order to assess
the tolerability of repeated infusions of ISF35 and to test whether additional
administrations will enhance the anti-leukemic activity exhibited in the previous Phase I

Inclusion Criteria:

1. Subjects must have been enrolled and tolerated the single dose ISF35 in MDACC
Protocol 2004-0914.

2. Subjects must have adequate Ad-ISF35 transduced CLL B cells to allow for at least one
additional treatment.

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.

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 give written informed consent for the Phase 1B extension trial.

Exclusion Criteria:

1. Unresolved toxicity (Grade ≥ 2) from single administration of Add-ISF35 transduced
autologous CLL B cells.

2. Presence of more than 55% prolymphocytes.

3. 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.

4. Ongoing toxicity from prior anti-neoplastic therapy.

5. Prior gene therapy (EXCEPT Ad-ISF35) or allogeneic stem cell transplantation.

6. Untreated autoimmune hemolytic anemia or immune thrombocytopenia.

7. Active infection requiring parenteral antibiotics.

8. HIV/HBV/HCV seropositivity.

9. 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 the repeat administration of 1x10^8, 3x10^8, or 1x10^9 autologous Ad-ISF35-transduced CLL B cells in up to 9 patients with CLL who tolerated previous treatment in MDACC Protocol 2004-0914.

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:

May 2007

Completion Date:

September 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