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
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
Duration of the trial
William G. Wierda, M.D., Ph.D.
M.D. Anderson Cancer Center
United States: Food and Drug Administration
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