BrUOG 273:Cellular Immunotherapy For Refractory Hematological Malignancies:A Brown University Oncology Research Group Study
There have been important advances in the modulation of the immune system for the treatment
of hematologic malignancies and solid tumors.
This protocol will build upon these previous observations as follows:
- Haploidentical peripheral blood pheresed cells will be used at 1-2x108 CD3 cells/kg.
- Total body radiation will not be utilized.
- This modification may more effectively activate the recipient's immune system to
attack their hematological malignancy by not damaging the recipient's immune cells
prior to cellular infusion. Safety should be improved since the risk of graft
versus host disease should be greatly reduced as the host's immune system will not
- G-CSF priming will not be used.
- In our first clinical trial, G-CSF priming was not used for matched transplants.
Our second trial did employ G-CSF priming in the haplo-identical setting. Previous
data has cited a role for G-CSF in stimulation of invariant NK cells with enhanced
GVL effects11. However, our most recent laboratory data with unprimed PBMC has
shown effective cell kill activity without the addition of G-CSF. As G-CSF would
be administered to healthy volunteers, the unclear benefit of the addition of this
cytokine is offset by the potential side effects such as headache, fever, and bone
pain. G-CSF mobilization serves to shift the response from a TH1 to TH2 through
the increased production of T regulatory cells. The end result would be a decrease
in immune stimulation. Since the goal of this study is to NOT have engraftment,
the manipulation of the donor cells to dampen the host versus tumor stimulation is
not needed nor desired. Furthermore, since this protocol is not a stem cell
transplant, stem cells do not need to be mobilized with G-CSF.
It is important to note that the proposed study is not a stem cell transplant study. In the
situation of stem cell transplants, the goal of the procedure is to have engraftment, or
sustainable donor chimerism in the marrow to provide hematopoietic reconstitution as well as
immunologic reconstitution. In this study, we are evaluating the use of donor lymphocytes
(not stem cells) to stimulate an immune response of the recipients' immune system.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To assess the response rate of cellular immune therapy with HLA haploidentical peripheral blood pheresed cells in patients with relapsed/refractory hematological malignancies.
8 weeks after infusion then 6 months after and every 4 months for approximately 2 years
Peter Quesenberry, MD
United States: Food and Drug Administration
|Rhode Island Hospital||Providence, Rhode Island 02903|
|The Miriam Hospital||Providence, Rhode Island 02903|