Adoptive Cell Therapy for B-Cell Malignancies After Allogeneic Hematopoietic Stem Cell Transplantation With Costimulated, Tumor-Derived Lymphocytes
- The prognosis for patients with B-cell lymphoid malignancies (BCL) with relapse or
refractory disease after allogeneic hematopoietic stem cell transplantation (AlloHSCT)
is poor. Effective therapy for patients who fail withdrawal of immune suppression and
administration of donor lymphocyte infusions (DLI) has not been identified.
- In the setting of recurrent or refractory BCL, the immunologic graft-versus-tumor (GVT)
effect generated by unmanipulated donor lymphocytes is often not durable and can be
accompanied by graft-versus-host disease (GVHD).
- We have hypothesized that lymphocytes found in tumor after alloHSCT are of donor
origin, and because they are tumor-derived, they may be tumor-specific in their homing
and antigen specificity characteristics. Similarly, inpatients with bone marrow
involvement with tumor, the marrow may be enriched with similarly tumor-specific T
cells. Further, activation and expansion of these cells through CD3/CD28 costimulation
may yield a more effective form of cell therapy than DLI after alloHSCT, with enhanced
GVT effects and less GVHD.
- To evaluate the feasibility of isolating and expanding clinically relevant numbers of
TDL from patients after alloHSCT.
- To determine the safety, vis-a-vis infusion toxicities and/or GVHD, of administering
- Adults with B cell malignancies with tumor that has not responded to successful T cell
engraftment after alloHSCT, withdrawal of immune suppression and administration of
donor lymphocyte infusion will be eligible for this trial.
- Subjects must have a minimum of 1.5 cm of accessible tumor which is amenable to
resection with minimal surgical morbidity and/or bone marrow tumor involvement.
- Subjects will have accessible lesion surgically resected and/or harvested via bone
- Lymphocytes will be liberated and expanded using a co-stimulatory approach with
anti-CD3/CD28 magnetic beads to generate TDL and/or marrow-TDL.
- 1.0 x 10(6) - 1.0 x 10(8) TDL will be administered.
- Subjects will be monitored for the development of infusion reactions (in-hospital for
24 hours after infusion), GVHD (weekly for four weeks then monthly) and tumor responses
- Two cohorts will be enrolled, with an arm evaluating TDL from resected tumor and an arm
to evaluate marrow-TDL from tumor-involved bone marrow. For the TDL arm, 15 to 18
patients and up to 18 donors will be enrolled; for the marrow-TDL arem, 15 patients and
up to 15 donors will be enrolled. Both arms will test the primary endpoints of
feasibility (with at least 11 of 15 tumors yielding 1.0 x 10(6) TDL/kg meeting defined
release criteria) and safety (primarily defined as having a no greater risk of
developing grade II-IV acute GVHD by day 28 as standard therapy with unmanipulated
Primary Purpose: Treatment
To evaluate the feasibility of administering ex-vivo costimulated/expanded tumor-derived lymphocytes (TDL) in patients with persistent or recurrent B-cell lymphoid malignancies (BCL) following treatment with allogeneic hematopoietic stem cell tr...
Elise C Kohn, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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