Recently, at the 12th International Conference on Malignant Lymphoma, Dr. Peter Martin, presented preliminary results from a phase I study evaluating palbociclib (also known as PD 0332991) combined with bortezomib in patients with previously treated mantle cell lymphoma. Mantle cell lymphoma is characterized by genetic changes that result in loss of cell cycle control, resulting in unrestrained cell proliferation. Palbociclib is an oral drug that specifically inhibits CDK4, enzyme that is central to the proliferation of mantle cell lymphoma cells. Data from WCMC demonstrated that palbociclib could arrest the growth of mantle cell lymphoma cells and that prolonged growth arrest could sensitize the cells to killing by low doses of bortezomib, thereby potentially improving its efficacy and tolerability. In our recent oral presentation at the ICML, we reported that palbociclib could be safely combined with low-dose bortezomib and that the combination appeared to have promising efficacy. Our results suggest that strategies to control the cell cycle should be explored.
For a full listing of all current clinical trials underway in the Lymphoma Program, please click here.
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 email@example.com.
- 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
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.
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.
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.