Conditions: Multiple Myeloma
Keywords: relapsed multiple myeloma refractory multiple myeloma LDE225 Sonidegib bortezomib smoothened (SMO) inhibitors Velcade
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 7
Healthy volunteers: no

Brief summary:
The purpose of the study is to determine whether the combination of LDE225 (sonidegib) plus bortezomib is safe and effective in the treatment of relapsed or relapsed/refractory multiple myeloma.

Detailed description:
Although multiple myeloma (MM) is considered fatal, survival has dramatically improved with the introduction of more effective treatment options. Despite these advances, all patients eventually relapse and MM is generally considered incurable. LDE225 (Sonidegib) is an oral, investigational smoothened (SMO) inhibitor that has shown anti-tumor activity in certain cancers. Bortezomib is a highly active drug for the treatment of MM and has produced response rates in relapsed and/or refractory patients. This study will investigate the tolerability and feasibility of combining LDE225 with bortezomib in patients with bortezomib-sensitive relapsed or relapsed/refractory MM.

Arms:
arm 1: Lead-In Portion: The lead-in portion of this study will investigate the safety and tolerability, and determine the MTD of LDE225, in combination with bortezomib in this patient population.

Expansion Portion: Eligible patients will receive LDE225 orally once daily for 21 days with the dose-level determined in the lead-in portion of the study. Eligible patients will also receive a standard regimen of bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of each 21 day cycle.

Maintenance Therapy: Patients who complete 16 cycles of therapy with stable disease or better will be eligible for single agent maintenance therapy of LDE225 at the MTD orally for up to 2 years or until progressive disease or unacceptable toxicity.

Interventions: intervention 1: LDE225 intervention 2: Bortezomib
Intervention descriptions: intervention 1: Lead-In: LDE225 will be administered orally at three dose levels starting at 400mg. If acceptable tolerability is demonstrated, escalations may continue up to 800 mg. LDE225 will be administered orally as a single daily dose for 21 days in combination with a fixed dose of bortezomib to be given on Days 1, 4, 8, 11 of each 21 day cycle.

Dose Expansion: LDE225 will be given as a single oral daily dose for 21 days at the MTD determined in the lead-in phase.

Maintenance Therapy: Patients who complete 16 cycles of therapy with stable disease or better will be eligible for single agent maintenance therapy of LDE225 at the MTD orally for up to 2 years or until progressive disease or unacceptable toxicity. intervention 2: In both the lead-in and dose expansion portions of the study, bortezomib, 1.3 mg/m2, will be administered by subcutaneous injection (SQ) on Days 1, 4, 8, 11 of each 21 day cycle.

Protocol document: