Tag: mantle cell lymphoma

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: Rituximab,Bendamustine Hydrochloride & Bortezomib Followed by Rituximab & Lenalidomide in Older Patients with Untreated Mantle Cell Lymphoma

E1411: Intergroup Randomized Phase II Four Arm Study In Patients > 60 With Previously Untreated Mantle Cell Lymphoma Of Therapy With: Arm A = Rituximab+ Bendamustine Followed By Rituximab Consolidation (RB → R); Arm B = Rituximab + Bendamustine + Bortezomib Followed By Rituximab Consolidation (RBV→ R), Arm C = Rituximab + Bendamustine Followed By Lenalidomide + Rituximab Consolidation (RB → LR) or Arm D = Rituximab + Bendamustine + Bortezomib Followed By Lenalidomide + Rituximab Consolidation (RBV → LR)

The Weill Cornell Lymphoma Program has recently opened a new clinical trial for men women age 60 and older with mantle cell lymphoma (MCL) that has not been previously treated. The study sponsor is the Eastern Cooperative Oncology Group. The principal investigator at Weill Cornell is Dr. Peter Martin. 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

  • Men and women age 60 and older
  • Mantle cell lymphoma (MCL)
  • No prior therapy for MCL
  • Detailed eligibility reviewed when you contact the study team

Study Details

The study has two steps of treatment:

Step 1: The purpose of Step 1 is to determine the effectiveness of the addition of bortezomib (also called Velcade) to rituximab plus bendamustine, compared to rituximab plus bendamustine alone.

Step 2: The purpose of Step 2 is to determine the effectiveness of continuing treatment after Step 1 with lenalidomide plus rituximab, compared to continuing with rituximab alone.

Study participants will be randomly assigned to one of four treatment regimens:

  • Group 1: Step 1 rituximab plus bendamustine, followed by Step 2 rituximab for up to 2 years
  • Group 2: Step 1 bortezomib plus rituximab and bendamustine, followed by Step 2 rituximab for up to 2 years
  • Group 3: Step 1 rituximab plus bendamustine, followed by Step 2 lenalidomide plus rituximab for up to 2 years
  • Group 4: Step 1 bortezomib plus rituximab and bendamustine, followed by Step 2 lenalidomide plus rituximab for up to 2 years

Although each of the drugs used in the study are FDA-approved to treat blood cancers, the combinations used in this study have not been FDA-approved and are considered experimental.

Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as bendamustine, also work in different ways to kill cancer cells or stop them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stop the growth of mantle cell lymphoma by blocking blood flow to the cancer. It is not yet known whether giving rituximab together with bendamustine and bortezomib is more effective than rituximab and bendamustine, followed by rituximab alone or with lenalidomide in treating mantle cell lymphoma.

Treatment Plan

Participants will be asked to take 6 cycles (6 months) of chemotherapy in Step 1. Participants in Groups 1 and 2 will take rituximab every 8 weeks for 2 years. Participants in Groups 3 and 4 will take 24 cycles (2 years) of lenalidomide plus rituximab.

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.