Category: Laboratory Research

New Clinical Trial: A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of LAM-002A Administered Orally in Subjects with Relapsed or Refractory B-cell non-Hodgkin Lymphoma

The Weill Cornell Medicine Lymphoma Program has recently opened a new clinical trial for men and women with previously-treated B-cell non-Hodgkin lymphoma. (B-cell NHL) The study sponsor is LAM Therapeutics, and the principal investigator at Weill Cornell is Sarah Rutherford, M.D.. For more information about the study, please call Rita Gazivoda, RN at 212-746-0702 or e-mail Rita at rig9021@med.cornell.edu.

Study Summary

This clinical trial is for men and women with B-cell non-Hodgkin lymphoma (B-cell NHL) who were previously treated for this disease.

Management of patients with non-Hodgkin lymphoma varies widely depending on histology. Patients with DLBCL who relapse after, or who are not candidates for ASCT, as well as patients with relapsed mantle cell lymphoma, marginal zone lymphoma, follicular lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) are not considered curative with conventional therapies. Therefore management of relapsed and refractory NHL remains an unmet medical need.

This is a Phase 1, single-arm, open-label dose-escalation study of the safety and pharmacokinetics of LAM-002A administered orally in subjects with relapsed or refractory B-cell NHL. There will be a dose-escalation stage and an expansion stage for this study. The study drug will be administered on a twice daily oral dosing regimen with a cycle length of 28 days. Patients will continue on treatment as long as they are responding to therapy and not experiencing unacceptable side effects. All patients will be followed for overall survival every three months via telephone contact during the post-treatment follow-up period.

Key Eligibility

  • Men and women age 18 and older with histologically confirmed diagnosis of B-cell NHL limited to follicular lymphoma, DLBCL, mantle cell lymphoma, marginal zone lymphoma, or CLL/SLL.
  • Prior therapy must have included a rituximab-based chemo-immunotherapy regimen.
  • Detailed eligibility reviewed when you contact the study team.

Unmasking a Killer: How Immunotherapy Helps Your Body Find Cancer and Destroy It

One of the difficulties in treating all cancers is the inability of a person’s immune system to target cancer cells because of the cancer cells ability to avoid detection. Researchers throughout the Meyer Cancer Center at Weill Cornell Medicine and NewYork-Presbyterian have been researching new ways to help the immune system find these cancer cells. This field of research is known as immunotherapy. Immunotherapy is a type of biological therapy that helps the immune system fight cancer through the use of substances in the living organism. You can find more information and an explanation as to how immunotherapy fights cancer in the below video:

http://www.nyp.org/cancerunmasked/

While specific immunotherapy derived treatments are still in the clinical trial phase for lymphoma this is an area of active research. In this video Lymphoma Program Director, Dr. John P. Leonard refers to the development of immune checkpoint inhibitors as an, “…important new frontier…” in the treatment of lymphoma. Currently clinicals for lymphoma related immunotherapy are ongoing. Available trials for immunotherapy at Weill Cornell can be found on the Joint Clinical Trials website.

Targeting New Pathways for the Treatment of an Aggressive Form of B-Cell Lymphoma

lecBy Leandro Cerchietti, MD

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and fast-growing lymphoma that is the most common form of non-Hodgkin lymphoma in the United States. Nearly 1/3 of DLBCL patients experience relapse. The outcome can be worse for patients with DLBCL that harbor activation of multiple oncogenes. An oncogene is a gene that can “hit” a cell to transform it into a cancer cell. Some cells are “hit” with more than one oncogene. When hit by two or three oncogenes they transform into a very aggressive lymphoma called double-hit and triple-hit lymphomas (DH/TH). These DH/TH are largely insensitive to combinatorial chemotherapy and are more frequently found in the elderly. To grapple with the complexities of treatment of DH/TH lymphomas, alternate pathways for the development of future treatments must be found by researchers.

The three oncogenes that could drive these lymphomas are MYC, BCL2 and BCL6, but it is not know whether all three work simultaneously. In a paper recently published in OncoTarget, researchers from my lab at Weill Cornell Medicine found that DLBCL cells that survive BCL6 targeted therapy induce a phenomenon of “oncogene-addiction switching” and super activate one of the other oncogenes, preferentially BCL2. The activation of BCL2 by the anti BCL6 therapy allows lymphoma cell to survive this targeted treatment. My team found that to be effective in killing lymphoma cells a therapy should inhibit both the BCL6 and BCL2 oncogenes.

This phenomenon occurs because these three oncogenes share the regulation of common pathways responsible for the survival of DLBCL. If one oncogene is targeted, the others can take the leading role. In the case of BCL6, specific targeting of BCL6 releases BCL2 inducing on-target feedback resistance to this therapeutic strategy. However, this “oncogene-addiction switching” mechanism can be harnessed to develop rational combinatorial therapies for DLBCL.

An alternative strategy to target DH/TH DLBCLs could be to simultaneously dismantle all three oncogenic networks. In a separate paper recently published in Blood, researchers from my lab and the University of Montreal found another potential therapeutic pathway for the treatment of these aggressive DLBCLs. They found that the protein Hsp90 binds to and maintains activity in eIF4E a protein that controls MYC, BCL6, and BCL2 networks. Inhibition of eIF4E using the antiviral drug Ribavirin decreases simultaneously MYC, BCL6, and BCL2 avoiding “oncogene-addiction switching” and inducing regression of DH/TH DLBCLs. The researchers used a novel pre-clinical model of lymphoma called “patient-derived tumorgrafts”, that are mouse models faithfully resembling the complexity of human lymphomas.

They also found that DH/TH could be targeted with Hsp90 inhibitors. Still targeting Hsp90 activity has met with limited success in the past due to the counter regulatory elevation of Hsp70, which induces resistance to Hsp90 inhibitors. However, researchers were able to identify Hsp70 as a target for eIF4E. Accordingly the combination of eIF4E and Hsp90 inhibitors should result in a potential new pathway for the development of new treatments for DLBCL, an approach WCM clinicians will test in future clinical trials.