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 firstname.lastname@example.org.
- 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.
By Peter Martin, MD
Update: this study is closed to enrollment.
Arguably the most exciting news to come from the American Society of Hematology (ASH) meeting this year was the presentation by Dr. Michael Wang of preliminary results from the phase 2 trial of PCI-32765 for patients with previously treated mantle cell lymphoma (MCL). PCI-32765 is an oral (pill form) inhibitor of an enzyme called Bruton’s Tyrosine Kinase (BTK). BTK plays an important role in communicating pro-survival signals from the cell microenvironment to the nucleus of the cell. Inhibition of BTK by PCI-32765 demonstrated promise in patients with MCL in a national phase 1 that was open at Weill Cornell Medical College. This phase 2 study, also open at Weill Cornell, demonstrated a response rate of approximately 60-70% with little toxicity (mostly mild gastrointestinal side-effects). It is too early to determine how long these effects will last or whether there are any side effects that will become apparent with longer treatment. Click here for more information about this trial.
Dr. Beata Holkova presented the results of a National Cancer Institute (NCI) phase 2 study that was open at several institutions across the country, including Weill Cornell. The trial evaluated the combination of bortezomib (FDA-approved for treatment of patients with previously treated MCL) plus the histone deacetylase inhibitor vorinostat. The combination demonstrated synergistic activity in preclinical studies and showed promised in earlier trials in patients with multiple myeloma. Preliminary results from this NCI trial were encouraging, particularly in the group of patients with MCL that had never been treated with bortezomib. The trial is ongoing. Click here for more information about this study.
By Peter Martin, MD
Until recently, the role of rituximab in treatment of mantle cell lymphoma (MCL) was unclear. Prior randomized trials demonstrated improved response rates to chemotherapy when combined with rituximab, but unlike other lymphomas, it had failed to demonstrate an improvement in survival. Two abstracts presented at the recent American Society of Hematology (ASH) meeting provided encouraging evidence regarding this most-important outcome.
Dr. Simon Rule presented the results of the recent UK National Cancer Research Institute trial comparing fludarabine/cyclophosphamide (FC) to FC plus rituximab (FCR) in patients of all ages with newly diagnosed MCL. The trial enrolled 370 patients with mostly intermediate and high-risk MCL and followed them for an average of 39 months. The addition of rituximab to FC improved response rate, complete response rate, time to progression, and overall survival. Combined with recent evidence from data registry studies and the data that has accumulated from prior trials, it is clear that standard of care first-line treatment of MCL should include rituximab.
Updated results from a European Mantle Cell Lymphoma Network trial (also presented at the meeting in Lugano last summer and discussed by Dr. Rebecca Elstrom in this blog) confirmed that rituximab maintenance administered to patients over 60 years of age after R-CHOP chemotherapy provided a significant survival benefit. Although longer follow-up and confirmatory trials are needed, rituximab maintenance may be considered standard of care for older patients not receiving more aggressive induction/consolidation regimens. The upcoming Intergroup trial for patients over 60 years of age will feature randomization between rituximab maintenance and maintenance with lenalidomide plus rituximab.