This is a phase 1, multicenter, open-label study evaluating the safety and efficacy of ruxolitinib, steroids and lenalidomide among MM patients who currently show progressive disease.
Name: Ruxolitinib Oral Tablet [Jakafi]
Description: Ruxolitinib will be administered on days 1-28 of the treatment cycle.Type: DrugRux Len and Steroid Rux and Steroid until progression, then add Len
Name: Lenalidomide
Description: Lenalidomide will be administered on Days 1-21 of the treatment cycle.Type: DrugRux Len and Steroid Rux and Steroid until progression, then add Len
Name: Methylprednisolone
Description: Methyl-prednisolone will be administered on Days 1-28 of the treatment cycle.Type: DrugRux Len and Steroid Rux and Steroid until progression, then add Len
Description: MTD will be determined by measuring incidence of the dose-limiting toxicities (DLTs) per dose level, of ruxolitinib in combination with steroids and lenalidomide for MM patients currently with progressive disease.
Measure: Determination of maximum tolerated dose (MTD) of ruxolitinib in combination with steroids and lenalidomide [Tolerability]. Time: 30 monthsDescription: Safety will be measured by counting the occurrence of adverse events throughout the study, graded via Common Terminology Criteria for Adverse Events (CTCAE) v 4.03 criteria
Measure: Incidence of Treatment-Emergent Adverse Events [Safety] Time: 54 monthsDescription: Overall response rate (ORR) is defined as CR + VGPR + PR
Measure: Overall response rate (ORR) as a measure of efficacy Time: 54 monthsDescription: Clinical benefit rate is defined as ORR + MR
Measure: Clinical benefit rate (CBR) as a measure of efficacy Time: 54 monthsDescription: Progression-free survival will be measured in months as the time from initiation of therapy to progressive disease or death from any cause, whichever occurs first
Measure: Progression Free Survival (PFS) Time: 54 monthsDescription: Time to response, defined as the time from the initiation of therapy to the first evidence of confirmed clinical benefit defined as > minimal response (MR, including patients who achieved a complete response (CR), very good partial response (VGPR), partial response (PR), or MR
Measure: Assessment of the time to response as a measure of efficacy Time: 54 monthsDescription: Duration of response, defined as the time (in months) from the first response to progressive disease
Measure: Assessment of the duration of response as a measure of efficacy Time: 54 monthsDescription: Overall survival, defined as the time (in months) from initiation of therapy to death from any cause or last follow-up visit
Measure: Assessment of the overall survival (OR) as a measure of efficacy Time: 54 monthsDescription: Response to initial therapy (ruxolitinib and methylprednisolone alone) will be compared to the response to therapy with addition of lenalidomide (ruxolitinib, lenalidomide, methylprednisolone)
Measure: Assessment of response in additional cohort Time: 54 monthsAllocation: Non-Randomized
Sequential Assignment
There is one SNP
The activating JAK2 V617F mutation results in uncontrolled cytokine and growth factor signaling, and is believed to play a key role in the pathophysiology of myeloproliferative neoplasms. --- V617F ---