Weill Cornell Research: ALK Inhibitors Completely Eradicate DLBCL with ALK Translocation in Laboratory Animals

In a significant finding recently published in PLoS One, researchers at Weill Cornell Medical Center showed that ALK inhibitors (drugs that act on tumors with the protein ALK) could completely eradicate Diffuse Large B-Cell Lymphoma (DLBCL) with ALK mutation in laboratory animals. This is an important finding considering that patients with DLBCL with ALK mutations are resistant to common chemotherapy treatments.

Patients diagnosed with ALK positive DLBCL may, therefore, be candidates for therapeutic trials of ALK inhibitors. The incorporation of ALK status determination into the diagnosis of DLBCL could help identify these patients more readily. There are several ALK inhibitors under clinical testing for ALK positive tumors.

Background

BCL6 is the most frequent oncogene (a gene that has the ability to cause cancer) in Diffuse Large B-Cell Lymphoma (DLBCL). However in a proportion of DLBCL other genes play a leading role in the oncogenic process. In an effort to personalize the treatment for patients with DLBCL, we found that a protein called ALK plays an oncogenic role in a subset of DLBCL.

We established and characterized the first ALK positive DLBCL line with a mutation that causes ALK to be expressed and active at very high levels, causing tumor cells to proliferate (reproduce rapidly). This cell line was obtained from the bone marrow tissue of a patient diagnosed with DLBCL. We developed pre-clinical animal models of DLBCL with ALK mutation, and we treated them with specific ALK inhibitors. As described above, the research showed that ALK inhibitors could completely eradicate DLBCL with ALK mutation in animals.

Click here to read the published research paper.

Clinical Trial Available for Untreated DLBCL

Early Response Assessment in Patients with Diffuse Large B-Cell Lymphoma Using 18-fluoro-2-deoxyglucose positron emission tomography (FDG-PET)

Update: this study is closed to enrollment. 

Although many patients with diffuse large B cell lymphoma are cured with initial treatment, some patients do not respond well to therapy, or they relapse after an initial response. Certain factors have been shown to predict the probability of responding well, but they are not able to define whether an individual patient will respond well to treatment.

In this study, we are examining the ability of FDG-PET scanning early on in treatment to predict the ultimate outcome of that treatment in an individual patient. We hope to use the information gained in this study to individualize treatment in the future.

Key eligibility:

  • Diagnosis of CD20+ diffuse large B-cell lymphoma (DLBCL) of any stage, including subtypes:
  • Mediastinal large B-cell
  • Centroblastic
  • Immunoblastic
  • T-cell rich B-cellmed
  • Anaplastic B-cell lymphoma
  • No prior anti-lymphoma therapy

Click here for a more detailed description of this study or contact June Greenberg, RN at (212) 746-2651 or jdg2002@med.cornell.edu.

Study available for Patients with DLBCL

Phase I/II Trial of Azacytidine + R-CHOP in Diffuse Large B-Cell Lymphoma

Update: this study is closed to enrollment.

Significant progress has been made in treatment of diffuse large B-cell lymphoma (DLBCL), but some patients are still not cured of their disease. Recently, researchers have begun to understand how reversible changes in expression of genes contribute to development of cancer and allow cancer cells to become resistant to the effects of chemotherapy. These reversible changes are termed “epigenetics” since they do not involve mutations in genes themselves.

We are working to take advantage of the reversible nature of these changes by pre-treating patients with azacitidine, a drug which reverses epigenetic changes, before starting standard chemotherapy treatment. In this way, we hope to improve the sensitivity of lymphoma cells to chemotherapy.

Key eligibility:

  • Men and women age 18 and older
  • Diagnosed with Diffuse Large B-Cell Lymphoma (DLBCL)
  • Stage II, III or IV disease
  • No previous treatment
  • Detailed eligibility discussed when you contact the study team

For more information about this study, contact June Greenberg, RN at (212) 746-2651 or email June at jdg2002@med.cornell.edu.

Click here to view all our current trials for lymphoma and other cancers and blood disorders.