The Weill Cornell Lymphoma Program has recently opened a new clinical trial for men and women with T-cell lymphoma. The study sponsor is Memorial Sloan Kettering Cancer Center, and the principal investigator at Weill Cornell is Jia Ruan, M.D., Ph.D.. For more information about the study, please call Amelyn Rodgriguez, RN at (212) 746-1362 or e-mail Amelyn at email@example.com.
- Men and women age 16 and older.
- T-cell non-Hodgkin lymphoma (NHL).
- Complete or partial response to prior therapy.
- Eligible for stem cell transplant.
- No prior autologous or allogenic transplant.
This clinical trial is for men and women with T-cell non-Hodgkin lymphoma. The purpose of the study is to test the benefit of a chemotherapy drug called romidepsin in men and women who have undergone autologous stem cell transplant.
Romidepsin has been FDA-approved for treating relapsed T-cell lymphoma. It is possible that in people who are at risk of their disease coming back (relapse), romidepsin could be used to prevent or delay the T-cell lymphoma from returning. The study will determine if giving romidepsin after the autologous stem cell transplant is safe and will prevent or delay the T-cell lymphoma from returning.
Participants will receive high dose chemotherapy followed by the stem cell transplant. Between 42 and 80 days after the transplant, participants will receive their first dose of romidepsin via infusion. Participants will continue to receive romidepsin every other week until 1 year after the stem cell transplant. If a participant’s disease has not progressed 1 year after the transplant, he/she will continue on romidepsin for another year.
By Leandro Cerchietti, MD
Malignant T-cell proliferation, survival, and drug resistance are dependent on a combination of external stimuli delivered by the micro-environment. Previous research has shown that the transmembrane receptor integrin αvβ3 plays a crucial role in mediating the interaction of T-cell lymphoma (TCL) cells with external signals. Integrin αvβ3 ligands include extracellular matrix-associated signaling proteins and soluble factors such as thyroid hormones (TH). Having previously shown that TH stimulate the proliferation of TCL through complimentary intracellular pathways involving the αvβ3 integrin, we hypothesized that targeting integrin αvβ3 could represent a novel strategy in treating TCL patients in an abstract presented during ASH.
In determining whether αVβ3 integrin is of therapeutic benefit for TCL, xenografts were developed in SCID mice using CUTLL1 cells transfected with si-control, si-αV and si-β3, and monitored tumor growth and angiogenesis. CUTLL1 was found to transfect with si-αV and si-β3 developed significant smaller tumors than si-control. The translational impact of this strategy was determined through the effect of cilengitide, a selective αVβ3 integrin inhibitor in phase 3 for glioma, in pre-clinical models of PTCL-NOS, ALCL-ALK+ and ALCL-ALK-. Similarly to si-αV and si-β3 treated mice, the anti-lymphoma effect of cilengitide correlated with lower levels of angiogenesis and NFkB activation.
This allowed us to elucidate the mechanisms by which integrin αvβ3 activation increases TCL proliferation through the activation of pro-survival pathways in malignant T-cells, while promoting angiogenesis. In the course of our research we also found that the genetic and pharmacological targeting of integrin αvβ3 induces an anti-lymphoma effect in TCL, including ALCL-ALK + and ALCL-ALK- PDT models obtained from treatment refractory patients. Both of these findings present potentially new therapeutic targets for the treatment of patients with T-cell lymphoma.
By Jia Ruan, MD, PhD
Although Hodgkin Reed-Sternberg (HRS) cells comprise only a small number of tumor cells, their number is outweighed by their relative importance as the orchestrators of an inflammatory microenvironment that allows for the growth of Hodgkin Lymphoma (HL). The peritumoral CD4 and CD8 cells in patients with HL, display high expression of the receptor programmed death-1 (PD-1). PD-1 is involved in the functional impairment and “exhaustion” of T-cells. Recent data confirms that the effects of HL-mediated immune suppression may stretch beyond the tumor microenvironment, with reports of high levels of inflammatory cytokines and chemokines in patients with both newly diagnosed and relapsed HL.
In results presented from an abstract presented during the 2014 American Society of Hematology conference (ASH), we found that HL patients have evidence of chronic activation/exhaustion in their central memory and effector T-cells. Informed consent was requested for correlative blood testing was obtained from patients with both newly diagnosed and relapsed HL. For patients with progressive disease persistence of this phenotype is worthy of further investigation as to whether immune dysfunction results from or is caused by resistance to therapy. An answer to this question may provide the rationale for an immune targeted therapy in patients with relapsed or resistance HL.