A Phase I Extension Trial of Repeated Infusions of ISF35
The study is a Phase Ib extension trial that will assess the toxicity, tolerability, and safety of up to two repeated administrations of 1x10^8, 3x10^8, or 1x10^9 autologous Ad-ISF35-transduced CLL B cells given intravenously to patients with CLL who tolerated ISF35 in the prior Phase I infusion trial at M.D. Anderson.
|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 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|
- 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. [ Time Frame: Duration of the trial ] [ Designated as safety issue: Yes ]
- Assess the anti-leukemia activity of the repeat administration of Ad-ISF35 transduced CLL B cells by evaluating reduction in leukemia count, reduction in adenopathy and splenomegaly, and improvement in bone marrow function. [ Time Frame: Duration of the trial ] [ Designated as safety issue: No ]
- Assess the quality of life with repeat Ad-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:||May 2007|
|Study Completion Date:||September 2008|
|Primary Completion Date:||September 2008 (Final data collection date for primary outcome measure)|
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 trial.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00783588
|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|