A Phase I Trial of Autologous CLL B Cells Transduced to Express Chimeric CD154 (ISF35)
The study is a Phase I, dose-escalating, non-randomized, single institution clinical trial assessing the safety and efficacy of autologous Ad-ISF35-transduced CLL B cells administered as a single intravenous infusion in patients with chronic lymphocytic leukemia (CLL).
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Trial of Autologous CLL B Cells Transduced to Express Chimeric CD154 (ISF35)|
- 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. [ Time Frame: Duration of the trial ] [ Designated as safety issue: Yes ]
- Assess the anti-leukemia activity of a single intravenous dose by evaluating reduction in leukemia count, reduction in adenopathy and splenomegaly, and improvement in bone function. [ Time Frame: Duration of the trial ] [ Designated as safety issue: No ]
- Assess the quality of life with ISF35 treatment. [ Time Frame: Two months ] [ Designated as safety issue: No ]
- Assess pharmacodynamic endpoints including induction of T cell anti-leukemia immune responses, antibody production against autologous CLL B cells, and changes in bystander leukemia cell phenotype. [ Time Frame: Two months ] [ Designated as safety issue: No ]
|Study Start Date:||June 2006|
|Study Completion Date:||March 2008|
|Primary Completion Date:||March 2008 (Final data collection date for primary outcome measure)|
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.
|United States, Texas|
|University of Texas M.D. Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||William G. Wierda, M.D., Ph.D.||M.D. Anderson Cancer Center|