Dasatinib in Combination With Melphalan and Prednisone to Treat Relapsed and Refractory Multiple Myeloma Patients (D-MP)
Clinically demonstrated efficacy of Melphalan and Prednisone in MM subjects as well as the confirmed inhibitory effect of dasatinib on several tyrosine kinase receptors and pathways implicated in the pathophysiology of MM. Additionally, as a SRC inhibitor, dasatinib plays an important role on bone metabolism through inhibition of osteoclast-mediated bone resorption in vitro. Dasatinib could, thus, be beneficial on bone density of patients on study, through blockage of osteolysis and control of bone lesions.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Multicenter, Open-label, Phase Ii Study of Dasatinib in Combination With Melphalan and Prednisone (D-MP) in Advanced, Relapsed / Refractory Multiple Myeloma Patients|
- Partial response rate is a primary study endpoint. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
Evaluation of tumor status will be conducted at screening and anti-tumor treatment efficacy will be assessed at every cycle according to the International Uniform Criteria for Response in MM.
Safety and tolerability are a co-primary endpoint: incidence of grade 3-4 toxicities will support the decision to move to stage 2, together with PR rate once all the patients accrued to the first stage are evaluable.
- Secondary objectives are progression-free survival and overall survival [ Time Frame: 4 years ] [ Designated as safety issue: No ]
|Study Start Date:||February 2008|
|Study Completion Date:||May 2011|
|Primary Completion Date:||May 2011 (Final data collection date for primary outcome measure)|
100 mg QD continuously (from day 1 to day 28)Drug: melphalan
0,18 mg/Kg/day from day 1 to day 4 for 6 cyclesDrug: prednisone
1,5 mg/Kg/day from day 1 to day 4 for 6 cycles
Primary Objective: To determine whether the combination of dasatinib with melphalan and prednisone provides therapeutic benefits and is safe in patients with relapsed/refractory Multiple Myeloma.
Study design, dose and mode of administration, and duration of treatment: Multicenter, open-label, single arm, two-stage, Phase II study of dasatinib in combination with melphalan and prednisone (D-MP) in advanced, refractory MM patients. The three drugs will be concurrently administered through 6 cycles; each cycle will be 28 days long (1 cycle = 4 weeks), for a total of 24 weeks of treatment. The treatment schedule will be the following:
- Melphalan 0,18 mg/Kg/day from day 1 to day 4 for 6 cycles;
- Prednisone 1,5 mg/Kg/day from day 1 to day 4 for 6 cycles;
- Dasatinib 100 mg QD continuously (from day 1 to day 28). After the 6 cycles of D-MP treatment, Dasatinib will be continuously administered alone as maintenance, until occurrence of progressive disease, unacceptable toxicity or informed consent withdrawal.
This is a two-stage Phase II trial according to Simon with a bivariate endpoint design, by which treatment efficacy and safety are jointly evaluated. This design allows the trial to be early stopped after the first stage if the number of observed partial responses (PR) is inadequate and the number of observed toxicities is too high. In the first stage of the protocol 17 patients are required.
|Torino, Italy, 10126|
|Principal Investigator:||Mario Boccadoro, MD||Divisione Universitaria di Ematologia Ospedale Molinette di Torino|