An Open-Label, Randomized, Phase 2 Study to Assess the Effectiveness of RCHOP With or Without VELCADE in Previously Untreated Non-Germinal Center B-Cell-like Diffuse Large B-Cell Lymphoma Patients

Study Status

Open to Enrollment

Study Description

The purpose of this clinical trial, called the Pyramid study, is to determine whether the addition of Velcade to R-CHOP, a commonly used drug combination for patients with diffuse large B-Cell lymphoma, benefits patients with non-GCB diffuse large B-cell lymphoma.

Patients will be randomly assigned to one of two study arms:
  • Arm 1 (Active Comparator) R-CHOP
  • Arm 2 (Experimental) R-CHOP plus Velcade

Pyramid Trial Background

With increasing knowledge of cancer biology and availability of new drugs, it is expected that therapy will be increasingly tailored to individual patients’ tumor subtypes. Examples of this in breast cancer, colon cancer and CML have emerged over the past ten years. Often referred to as “personalized medicine” or “precision medicine”, this targeted approach to cancer therapy relies on translational research that defines a drug’s clinical activity in the context of the tumor’s cellular and genomic pathology.

Translational research has characterized the molecular basis of the clinical heterogeneity in various lymphomas, and many new agents are in development for lymphoma. Although the targeted development of these drugs in specific lymphoma patient subgroups could potentially speed their availability to the right patients, there are two major challenges to targeted trials in lymphoma. First, the empiric clinical research has led to highly active drug combinations that improve outcomes for many patients with lymphoma and in some specific types current therapy does in fact successfully treat a portion of the patients; leaving fewer patients with an unmet medical need to enter clinical trials. Second, it is a practical challenge to test and quickly identify specific lymphoma patient subgroups that can be enrolled in clinical trials of targeted drugs. Therefore a personalized study should ideally use a practical, rapid test to identify a lymphoma group that is not responsive to known treatment and test a therapy that targets an important pathway in those tumors.

The PYRAMID trial addresses both of these issues in order to test an investigational combination of R-CHOP with or without VELCADE, a known NFKB inhibitor, specifically in non-GCB lymphoma. The non-GCB subtype of DLBCL has been shown to be dependent on the NFKB pathway by numerous studies. Importantly, the NFKB pathway appears to be a major factor leading to the inferior outcomes of non-GCB (both progression free and overall survival) treated with R-CHOP therapy so there is good rationale to test NFKB inhibition in these patients. Therefore the PYRAMID study starts out by determining if a newly diagnosed patient has the GCB subtype or non-GCB subtype. Each group constitutes approximately 50% of DLBCL and the subtype results are available to the clinician in a few days. The non-GCB subtype is eligible for the PYRAMID study.

Click here to read more about the Pyramid study.

Disease Status and/or Stage

Previously untreated Non-Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma


Millennium Pharmaceuticals

Key Eligibility

  • Men and women age 18 and older
  • Previously untreated Non-Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma
  • Detailed eligibility discussed when you contact the study team
  • Principal Investigator

    John Leonard, MD


    Healthy Volunteers


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    Contact Us

    For general inquiries, or if you need assistance finding a study, please contact:

    Robert Hagerty
    Subject Recruitment Manager
    Tel: (646) 962-9340
    [email protected]

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