Phase I/II trial of Lenalidomide plus Bortezomib combined with Dexamethasone in patients in 1st relapse or primary refractory after first line therapy for Multiple Myeloma.

Study phase: Phase I - II

Study objective:

Evaluation of the effect of Bortezomib combined with Lenalidomide in addition to Dexamethasone for induction and the effect of Lenalidomide alone for maintenance treatment


Patient population:
Patients with multiple myeloma, in 1st relapse or refractory after first line therapy, Salmon & Durie stage II or III, age 60-85 years inclusive


Study design:
Prospective, multicenter
Duration of treatment: Expected duration of induction is 6 - 7 months. Maintenance therapy with Lenalidomide will be given until relapse/progression. All patients will be followed until 5 years after registration or, for patiens who are still on maintenance at that moment, until completion of maintenance therapy

Phase II part:

- Null hypothesis (H0):

(s)CR+VGPR rate = 15%

- Alternative hypothesis (H1):

(s)CR+VGPR rate = 30%

- At entry

- After each induction cycle (Expected duration of induction is 6 - 7 months.)

- During maintenance and follow up: every 2 months. (All patients will be followed until 5 years after registration or, for patiens who are still on maintenance at that moment, until completion of maintenance therapy
)

During the phase I part of the study, the MTD and RDL of Bortezomib and Lenalidomide with Dexamethasone will be determined according to a slightly modified `3 + 3’ dose-escalation scheme, as illustrated in the figure below. A maximum of 4 dose levels will be evaluated.



When the phase I part has established the RDL of Bortezomib and Lenalidomide for the phase II study, all further included patients will be treated with Bortezomib and Lenalidomide at the RDL, combined with Dexamethasone.