This Phase I-II dose-finding trial to determine the optimal dose of intravenous (IV) injection dose of donor-derived cytotoxic T lymphocytes (CTLs) specific for CMV, EBV, BKV and Adenovirus. A maximum of 36 patients will be treated in up to 18 cohorts each of size 2, with the first cohort treated at the lowest dose level 1, all successive doses chosen by the EffTox method, and no untried dose level skipped when escalating.
The scientific goal of the trial is to determine an optimal IV-CTL cell dose level among the three doses 1.0x107cells/m2, 2 x107cells/m2 and 5x107cells/m2., hereafter dose levels 1, 2, 3. Dose-finding will be done using the sequentially adaptive EffTox trade-off-based design of Thall et al.
Pediatric and adult patients (there are no lower and upper age limits for patients) with malignant or nonmalignant diseases who are candidates for transplant.
be cryopreserved in two fractions, with a minimum of 2.5x107 total nucleated cells (TNC) per kg pre-thaw in the fraction which will be used for the primary transplant. The remaining fraction will be used to generate the CTLs to give at day 30 or beyond as described below. OR
be cryopreserved with a cell dose that totals > 3x10e7 TNC per kg pre thaw. On thaw, 20% of the total volume will be used for CTL manufacture to give at day 30 or beyond and the remaining 80% will be used for the primary transplant.
For recipients of double CBT, if possible both CB units should be cryopreserved in two fractions and T-cells will be made from both units if possible.
Pregnant or lactating
Patients with active central nervous system disease
Patients with Karnofsky performance status <70%
Patients with grade 3 or 4 or primary myelofibrosis
Single group
CMV/AdV /EBV/BKV specific T cells
Biological/VaccineEach cohort of 2 patients will be treated and observed for 45 days for toxicity, dose escalation, and GvHD. The algorithm of sequentially adaptive EffTox trade-off-based design of Thall et al will be used to determine the dose for each cohort. If 1x107CTL/m2 results in unacceptable toxicity or efficacy, the study will be closed to accrual.
Number of participants with investigational product-related adverse events as assessed by CTCAE v4.03
The study will determine the optimal dose of intravenous injection of donor-derived cytotoxic T lymphocytes (CTLs) specific for CMV, EBV, Adenovirus and BK virus( BKV) given to patients with or at risk for CMV, EBV, BK virus and adenovirus infection after cord blood transplant. The safety will be assessed by investigational product-related adverse events as per CTCAE v4.03.
Impact of CMV/AdV /EBV/BKV specific T cells will be measured by existence of cells in the system.
To evaluate the impact of CTLs on CMV/AdV /EBV/BKV -specific T-lymphocyte immune reconstitution. The impact will be evaluated by the number of months/years of cell survival.
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Catherine Bollard
Lead sponsor
Children's National Research Institute
Sponsor institution
M.D. Anderson Cancer Center
Collaborator
