Weill Cornell Breakthrough Research: Shutting Down DLBCL Master Protein; Potential for New Treatments

Reporting in Nature Immunology, Weill Cornell’s Dr. Ari Melnick and his research team have reported an important research breakthrough in diffuse large-B cell lymphoma (DLBCL) that may offer hope for new treatments for aggressive lymphomas.

Dr. Melnick has found that it is possible to shut down the protein Bcl6, a powerful master regulatory transcription factor that is the key to survival for many aggressive lymphomas arising from the B-cells.

“The finding comes as a very welcome surprise,” says the study’s lead investigator, Dr. Ari Melnick, Gebroe Family Professor of Hematology/Oncology and director of the Raymond and Beverly Sackler Center for Biomedical and Physical Sciences at Weill Cornell.

The protein Bcl6 was previously considered too complex to target with individual drugs, because of its centrality in the functioning of the body’s healthy immune cells.

“This means the drugs we have developed against Bcl6 are more likely to be significantly less toxic and safer for patients with this cancer than we realized,” says Dr. Melnick.

DLBCL is the most common subtype of non-Hodgkin lymphoma — the seventh most frequently diagnosed cancer, with many patients resistant to currently available treatments. Presently, there are ongoing clinical trials for those suffering from non-Hodgkin’s lymphoma and other forms of lymphoma at the Weill Cornell Lymphoma Center.

The full press release can be read here.

Ibrutinib Granted Breakthrough Status by FDA for Two B-Cell Malignancies

On February 12, the FDA granted a Breakthrough Therapy Designation for the investigational agent ibrutinib in the treatment of mantle cell lymphoma and Waldenstrom’s macroglobulinemia. This designation is awarded to drugs whose preliminary clinical evidence suggests an improvement over existing therapies on one or more clinically significant endpoints. Enacted as part of the 2012 FDA Safety and Innovation Act, the Breakthrough Therapy Designations were conceived to help speed along the drug development process, drastically decreasing the time between clinical trials and final regulatory approval.

Ibrutinib, an oral drug designed to specifically target an enzyme called Bruton’s tyrosine kinase (BTK), has demonstrated promising activity in multiple phase 1 and 2 clinical trials performed at Weill Cornell Medical College and around the world. As one of the leading institutions in the study of ibrutinib since its first trials 3 years ago, Weill Cornell is uniquely positioned in its experience with ibrutinib.

Currently, there are ongoing ibrutinib clinical trials at the Weill Cornell Lymphoma Center open to patients with CLL and mantle cell lymphoma. Please stay updated with our clinical trials listing for forthcoming trials with ibrutinib.

New Clinical Trial: GS-1101 in Combination with Bendamustine and Rituximab for Previously Treated CLL

Update: this study is closed to enrollment. 

The Weill Cornell Lymphoma Program is now recruiting men and women with previously treated, recurrent chronic lymphocytic leukemia (CLL) for a clinical trial evaluating the experimental drug GS-1101 (also called Idelalisib, formerly called CAL-101), combined with bendamustine and rituximab, in treating CLL. The study sponsor is Gilead Sciences, Inc, and the principal investigator at Weill Cornell is Dr. Richard Furman. For more information about the study, please call Amelyn Rodgriguez, RN at (212) 746-1362 or e-mail Amelyn at amr2017@med.cornell.edu.

Key Eligibility
  • Age 18 and older
  • Diagnosis of B-cell chronic lymphocytic leukemia (CLL)
  • Previously treated for CLL
  • Detailed eligibility reviewed when you contact the study team
Study Details

GS-1101 (CAL-101) is a pill designed to block some of the cell functions that cause CLL to grow and survive and may help control the disease. Rituximab and bendamustine are approved by the FDA as a treatment for CLL. The study will help determine whether adding GS-1101 (CAL-101) to the standard treatment of rituximab and bendamustine will have a better effect on controlling CLL.

Study participants will be randomly assigned to one of two treatment groups:

  • Group A: GS-1101 and rituximab/bendamustine
  • Group B: Rituximab/bendamustine and placebo (an inactive pill that looks like GS-1101 but contains no medicine)

After 20 weeks of therapy with rituximab, bendamustine and GS-1101 or placebo, participants will continue with GS-1101 or placebo as long as their CLL is controlled.