Study of Bendamustine, Lenalidomide and Low-dose Dexamethasone, for the Treatment of Patients With Relapsed Myeloma
This is an open Label, Phase I/II, multicenter study. In the first phase it defines the maximum tolerated dose (MTD) of Bendamustine (B) given in combination with Lenalidomide (L) and low-dose Dexamethasone (d) and in the second phase it evaluates the antitumour activity of Bendamustine, Lenalidomide and Low-dose Dexamethasone (BdL) given in combination, in relapsed multiple myeloma patients.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of Bendamustine, Lenalidomide and Low-dose Dexamethasone, (BdL) for the Treatment of Patients With Relapsed Myeloma.|
- Phase I:Determination of Maximum Tolerated Dose [ Time Frame: up to 28 days during first cycle ] [ Designated as safety issue: Yes ]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
- Phase I:Determination of occurrence rate of AE/SAEs [ Time Frame: up to 28 day (during the first cycle 1of BdL administered) ] [ Designated as safety issue: Yes ]To assess the Safety and Toxicity of the Bendamustine,Dexamethasone and Lenalidomide (BdL) regimen
- Phase II: Overall Response Rate (ORR) [ Time Frame: An avarage of 6 months (after 6 cycles of therapy) ] [ Designated as safety issue: No ]To assess the antitumour activity of the BdL regimen, in term of Complete response, Partial response and Stable disease, according to the best schedule identified during Phase I.
- Phase I: Assessment of the preliminary antineoplastic properties of the BdL [ Time Frame: after an avarage of 6 months ] [ Designated as safety issue: No ]To explore the preliminary antitumor activity of drug combination in patients with relapsed MM
- Phase II: AE/SAEs [ Time Frame: Every 28 days (during all cycles) ] [ Designated as safety issue: Yes ]To define the safety profile of the treatment assessing the occurrence rate and the severity
- Phase II:Determination of the response rates [ Time Frame: Assessed after 6 months ] [ Designated as safety issue: No ]To assess Partial Response and Complete Response rates
- Phase II:Time to Event parameters [ Time Frame: avarage 6 months ] [ Designated as safety issue: No ]To evaluate the efficacy of the BdL regimen in patients with relapsed MM, in terms of Progression-Free Survival, Time to Progression, Time to Response, Duration of Response ,Overall Survival(PFS, TTP, TTR, DR, OS)
|Study Start Date:||February 2010|
|Estimated Study Completion Date:||October 2013|
|Primary Completion Date:||April 2012 (Final data collection date for primary outcome measure)|
Experimental: Dose escalation benda lena dexa
Phase I: Participants will be treated in groups (cohorts) of three to six subjects per cohort, according to a modified Fibonacci design. The dose of Bendamustine and Lenalidomide (from 0 to 5) will be increased from one cohort to the next. Regardless of the treatment cohort, participants will receive treatment in cycles lasting 28 days. In the first phase of the study, the dose of B and L given with will be gradually escalated to reach the MTD.
Phase II: Dexamethasone will be given in combination with the MTD of Bendamustine and Lenalidomide in cycles lasting 28 days.
Phase I: dose escalation of Bendamustine Phase II: Dexamethasone will be given in combination with the MTD of Bendamustine and Lenalidomide in cycles lasting 28 days.Drug: Lenalidomide
Phase I: dose escalation of Lenalidomide Phase II: Dexamethasone will be given in combination with the Maximum Tolerated Dose (MTD) of Bendamustine and Lenalidomide in cycles lasting 28 days.Drug: Dexamethasone
Phase I and Phase II Dexamethasone fixed dose 40 mg/die
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.
|Contact: Fortunato Morabito, MDemail@example.com|
|Contact: Fortunato Morabito, MDfirstname.lastname@example.org|
|U. O. C. Ematologia - Azienda Ospedaliera Cosenza||Recruiting|
|Cosenza, Italy, 87100|
|Contact: Fortunato Morabito, MD +390984681329 email@example.com|
|Study Chair:||Fortunato Morabito, MD||Unità Operativa Complessa di Ematologia- Stabilimento Ospedaliero Annunziata - Azienda Ospedaliera di Cosenza|