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LCI-HEM-MYE-CRD-004 (MMRC-073 CARJAK): Study of CRD for Carfilzomib-Refractory Multiple Myeloma

Phase 1
Completed
Conditions
Multiple Myeloma
Interventions
Registration Number
NCT03773107
Lead Sponsor
Wake Forest University Health Sciences
Brief Summary

The primary objective of Phase I is to establish the maximum tolerated dose (MTD) of ruxolitinib in combination with carfilzomib and dexamethasone. The primary objective of phase II is to evaluate progression-free survival (PFS) at 4 months in multiple myeloma subjects who receive the combination treatment carfilzomib, dexamethasone, and ruxolitinib.

Detailed Description

This is an open-label, Phase I/II study of carfilzomib, ruxolitinib, and low-dose dexamethasone for carfilzomib-refractory multiple myeloma. Phase I is designed to evaluate overall maximum tolerated dose (MTD) of ruxolitinib in combination with carfilzomib and dexamethasone in the following cohorts: Cohort 1) 5mg ruxolitinib, Cohort 2) 10mg ruxolitinib, Cohort 3) 15mg ruxolitinib. Phase II is designed to evaluate 4-month progression-free survival (PFS) in the following cohorts: Cohort A) non-responders to Phase I regimen, Cohort B) responders to Phase I regimen. Up to 18 evaluable subjects will be enrolled in Phase I over approximately 12 months. An additional 30 evaluable subjects will be enrolled in Phase II over 24 months.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
12
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Phase IDexamethasoneCohort 1) 5mg ruxolitinib, Cohort 2) 10mg ruxolitinib, Cohort 3) 15mg ruxolitinib
Phase ICarfilzomibCohort 1) 5mg ruxolitinib, Cohort 2) 10mg ruxolitinib, Cohort 3) 15mg ruxolitinib
Phase IRuxolitinibCohort 1) 5mg ruxolitinib, Cohort 2) 10mg ruxolitinib, Cohort 3) 15mg ruxolitinib
Phase IICarfilzomibCohort A) non-responders to Phase I regimen, Cohort B) responders to Phase I regimen
Phase IIRuxolitinibCohort A) non-responders to Phase I regimen, Cohort B) responders to Phase I regimen
Phase IIDexamethasoneCohort A) non-responders to Phase I regimen, Cohort B) responders to Phase I regimen
Primary Outcome Measures
NameTimeMethod
Dose Limiting Toxicity (DLT)28 days

DLTs will be determined for each subject as a binary variable indicating whether or not the subject experienced a DLT during Cycle 1

Secondary Outcome Measures
NameTimeMethod
Clinical Benefit RateApproximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)

Clinical benefit will be determined for each subject as a binary variable indicating whether or not the subject achieved a best overall response of minimal response (MR) or better as determined by the IMWG criteria

Duration of Responseapprox. 5 years

Duration of response will be defined as the time from first objective status assessment of response to the time of first documented disease progression or death.

Disease Control RateApproximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)

Disease control will be determined for each subject as a binary variable indicating whether or not the subject achieved a disease response or stable disease for greater than or equal to 8 weeks

Progression-free Survival (PFS)approx. 5 years

PFS is defined as the duration of time from the initiation of study treatment with ruxolitinib to first occurrence of either progressive disease or death without progressive disease.

Objective Response Rate (ORR)Approximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)

Objective response will be determined for each subject as a binary variable indicating whether or not the subject achieved a best overall response of PR or better as per the IMWG criteria

Time to Best ResponseApproximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)

Time to best response will be defined as the time from initiation of ruxolitinib treatment to the time of best objective status assessment of response.

Overall Survivalapprox. 5 years

Overall survival is defined as the duration from initiation of ruxolitinib treatment to the date of death from any cause.

Time to Progressionapprox. 5 years

Time to progression (TTP) is defined as the duration of time from the initiation of study treatment with ruxolitinib to first occurrence of either progressive disease or death.

Trial Locations

Locations (2)

Karmanos Cancer Institute

🇺🇸

Detroit, Michigan, United States

Levine Cancer Institute

🇺🇸

Charlotte, North Carolina, United States

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