A Phase I/II Study of Bendamustine, Lenalidomide and Low-dose Dexamethasone, (BdL) for the Treatment of Patients With Relapsed Myeloma.
Multiple myeloma is a B-cell malignancy resulting from the monoclonal proliferation of
plasma cells within the bone marrow. According to the American Cancer Society, 14,600 new
cases of multiple myeloma will be diagnosed in 2002, and these will account for
approximately 1% of all new cancer cases. Multiple myeloma will contribute to 2% of all
cancer deaths this year; an estimated 10,800 deaths will occur overall. The disease is more
prevalent in men and is twice as common in African-Americans as in Caucasians. Multiple
myeloma is commonly thought of as a disease of older patients; the median age at diagnosis
is 68 years, and the incidence increases more than 4%/year in those older than 85 years. The
median survival with standard treatment is only 3 years.
Therapeutic options for patients with multiple myeloma (MM) are rapidly changing. The
emergence of two highly active novel agents, bortezomib and lenalidomide, have dramatically
changed the landscape of treatment options and have improved outcomes for many patients.
Combinations of conventional agents with novel agents have also demonstrated significant
efficacy for patients with newly diagnosed and relapsed myeloma. Among the conventional
agents that are being explored is the bifunctional alkylator agent bendamustine, which has
demonstrated single-agent activity and activity with novel agents.
Lenalidomide is a new immunomodulating agent effective in multiple myeloma, especially when
associated with dexamethasone or melphalan and prednisone. The role of lenalidomide in the
treatment of relapsed/refractory patients with MM has been established and current research
is focused on the combination of lenalidomide with chemotherapy to further improve results.
Bendamustine is a bi-functional alkylating agent with a purine- like benzimidazole ring that
has been administered successfully to patients with MM. In vitro studies showed that
bendamustine possesses a unique profile of activity, which was clearly divergent from other
common nitrogen mustard drugs. Bendamustine and prednisone in newly diagnosed MM patients
results in superior complete response rate, prolonged time to treatment failure and improved
quality of life compared to treatment with melphalan and prednisone. The role of
bendamustine, thalidomide and prednisolone (BPT) in patients with relapsed or refractory
diseases stage II/III has been investigated by the East German Study group of Hematology and
Oncology (OSHO). The response rate was higher than 80%.
Despite the impressive efficacy of the lenalidomide/dexamethasone in relapsed MM, treated
patients will eventually relapse (median Time to Progression (TTP) is expected to be nearly
a year according the results of the two phase III randomized studies). Combination with an
effective novel agent as bendamustine could further increase both the response rate and the
TTP of lenalidomide/dexamethasone and induce durable responses in relapsed or refractory MM
patients. The identification of an appropriate lenalidomide dose to be adopted in
combination with bendamustine and dexamethasone and the generation of exploratory data on
the efficacy of this novel combination appears to be important in terms of future
development of even more effective treatments of MM.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Phase I:Determination of Maximum Tolerated Dose
In the first phase of the study, the dose of Bendamustine and Lenalidomide given with will be gradually escalated to reach the Maximum Tolerated Dose. The Maximum Tolerated Dose of Bendamustine and Lenalidomide will be evaluated during the first course (cycle 1) of Bendamustine Dexamethasone Lenalidomide (BdL) administered
up to 28 days during first cycle
Fortunato Morabito, MD
Unità Operativa Complessa di Ematologia- Stabilimento Ospedaliero Annunziata - Azienda Ospedaliera di Cosenza
Italy: National Institute of Health