Tag: VELCADE

Weill Cornell Researchers: Velcade + PD 0332991 Weaken & Defeat Myeloma Cells, Potential for Lymphoma

In laboratory experiments, researchers at Weill Cornell Medical College have demonstrated that the cancer fighting effects of Velcade (bortezomib) and PD 0332991  were exponentially multiplied when used together in their laboratory studies on multiple myeloma tumor cells.

The normal cellular growth cycle is derailed in cancer. Uncontrolled growth and multiplication is often the result. The researchers found that PD 0332991 stops the cellular cycle in a vulnerable moment, leaving the cancer cell wide open for cellular destruction by Velcade.

The study, published online last month by the journal Blood, is the first to show that precise timing of therapies that target a cancer cell’s cycle — the life phases leading to its division and replication — disables key survival genes, resulting in cell death. The drug that delivers the weakening jab at the cell cycle is the experimental agent PD 0332991, which allows Velcade, a proteasome inhibitor already approved for use in myeloma and lymphoma, to land the final defeating blow at lower than normal doses.

Dr. Selina Chen-Kiang, professor of Pathology and Laboratory Medicine and of Microbiology and Immunology at Weill Cornell Medical College was the lead scientist on the study. In an interview Dr. Chen-Kiang said:

“Because robust functioning of the cell cycle is crucial to cancer growth and survival, this mechanism-based strategy could theoretically be used against many kinds of cancers.”

The same combination is being tested in patients with mantle cell lymphoma in a Weill Cornell investigator-initiated study led by Dr. John Leonard. Click here for more information about the mantle cell lymphoma study.

 

New Clinical Trial: Ofatumumab and Bortezomib in Untreated Waldenstrom Macroglobulinemia

A Multicenter Phase II Study of Ofatumumab and Bortezomib (OB) in Previously Untreated Patients with Waldenström Macroglobulinemia

Update: this study is closed to enrollment. 
The Weill Cornell Lymphoma Program is now enrolling patients in a new clinical trial for people with Waldenstrom Macroglobulinemia who have not been treated. The study sponsor is the National Comprehensive Cancer Network (NCCN). The principal investigator at Weill Cornell is Dr. Peter Martin.

For more information about the study, please call Amelyn Rodriguez, RN at (212) 746-1362 or email Amelyn at amr2017@med.cornell.edu.

Key Eligibility

  • Men and women age 18 and older
  • Diagnosis of Waldenstrom Macroglobulinemia (WM)
  • No prior anti-neoplastic therapy for WM
  • Detailed eligibility reviewed when you contact the study team

Study Details

Although there is currently no standard treatment for first-line management of WM, most clinicians and investigators believe that anti-CD20 directed therapy should compromise part of the regimen. Because it was the first therapeutic monoclonal antibody approved by the FDA , rituximab has been evaluated more than any antibody and has shown modest effects with limited toxicity. However, new treatments for WM are needed.

Ofatumumab has been approved for treatment of relapsed/refractory Chronic Lymphocytic Leukemia (CLL). It is an anti-CD20 monoclonal antibody that compared favorably to rituximab in a recent Phase 2 trial in patients with WM.

The purpose of the study is to determine how well previously untreated people with Waldenstrom Macroglobulinemia respond to treatment with ofatumumab in combination with bortezomib (Velcade). The study will also evaluate the safety of ofatumumab in combination with bortezomib.

Treatment Plan

Study participants will have four 28-day cycles of induction phase therapy. Participants will receive treatments weekly for three weeks, and then have a rest period (no treatment) for the fourth week. After the four cycles, there will be 4 weeks of no therapy and then 4 cycles of maintenance phase therapy. The maintenance cycles will be 28 days long. Participants will receive three weeks of treatment, then a resting period (no treatment) for the fourth week. This will be followed by four weeks of rest (no treatments). Then a new cycle will begin. Thus a new cycle of maintenance treatment will begin every 8 weeks. The entire period for both induction and maintenance therapy will be 1 year (52 weeks).

Participants will be followed until disease progression or 5 years from study entry, whichever comes first.

PYRAMID: A Personalized Medicine Study in Lymphoma

Update: this study is closed to enrollment. 

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.

Pyramid Trial Summary

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. Continue reading “PYRAMID: A Personalized Medicine Study in Lymphoma”