Study of High Dose Carfilzomib in Multiple Myeloma Patients Who Have Progressed On Standard Dose Carfilzomib
Relapse Multiple Myeloma
Refractory Multiple Myeloma
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Recapturing Disease Response: A Phase II Study of High Dose Carfilzomib in Patients With Relapsed or Refractory Multiple Myeloma Who Have Progressed on Standard Dose Carfilzomib|
- Safety and Efficacy of High Dose Carfilzomib [ Time Frame: up to 4 years ] [ Designated as safety issue: Yes ]To explore the safety and efficacy of high dose carfilzomib who developed disease progression on the standard dosing and schedule of carfilzomib
- markers of ER stress [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]a) To investigate the markers of ER stress signaling (both apoptotic and prosurvival) in MM cells from patients in this study and to determine if the balance of apoptotic versus prosurvival signaling changes upon recapture of response with carfilzomib dose escalation relative to the time of study entry.
- Exploring the Role of Salubrinal in Carfilzomib's efficacy [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]To investigate whether salubrinal can augment the effectiveness of carfilzomib by inhibiting the development of quiescence upon proteasome inhibition in MM cells obtained from patients enrolled in this study.
|Study Start Date:||September 2013|
|Estimated Study Completion Date:||August 2016|
|Estimated Primary Completion Date:||August 2016 (Final data collection date for primary outcome measure)|
All patients will receive Carfilzomib
During Cycle 1, patients will receive either 20 mg/m2 on days 1,2 (if the subject has not received carfilzomib as part another clinical trial within the last 4 weeks) or 56 mg/m2 (if the subject is enrolling in the present study after progression of disease on carfilzomib within the last month - for example subjects enrolled in CMAP compassionate use carfilzomib). Thereafter, all subjects will receive 56 mg/m2 for the remaining doses given Cycle 1 Day 8 onwards. Each cycle is 28 days.
Other Name: High Dose Carfilzomib
This is an open label, single center, phase II study of high dose carfilzomib. Patients with relapsed or relapsed/refractory myeloma and with progression of disease on standard dosing (20/27 mg/m2) and schedule of carfilzomib will be initially treated at dose level 1, carfilzomib 20/56 mg/m2. During Cycle 1, patients will receive either 20 mg/m2 on days 1,2 (if the subject has not received carfilzomib as part another clinical trial within the last 4 weeks) or 56 mg/m2 (if the subject is enrolling in the present study after progression of disease on carfilzomib within the last month - for example subjects enrolled in CMAP compassionate use carfilzomib). Thereafter, all subjects will receive 56 mg/m2 for the remaining doses given Cycle 1 Day 8 onwards. If a minimal response or better is achieved (and therefore disease response is recaptured) a bone marrow biopsy will be repeated.
If 56 mg/m2 is not tolerated, the dose of carfilzomib will be reduced to dose level -1 i.e. 45 mg/m2. If a subject does not tolerate 45 mg/m2 then the dose would be further reduced to dose level -2 i.e. 36 mg/m2. If the subject does not tolerate 36 mg/m2, then this subject would have to come off study.
Dexamethasone 8 mg po/IV will be administered prior to all carfilzomib doses.
Once a patient develops disease progression on this study, the patient may return to receiving the maximum tolerated dose of carfilzomib by that patient with the addition of a therapeutic dosing of dexamethasone (a total of 20-40 mg weekly). An IMId (e.g. thalidomide or lenalidomide) and/or an alkylator can also be added to carfilzomib 27 or 36 mg/m2 per investigator discretion either concurrent with the addition of dexamethasone or subsequent to disease progression on carfilzomib with concurrent therapeutic dexamethasone.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01775553
|United States, New York|
|Icahn School of Medicine at Mount Sinai|
|New York, New York, United States, 10029|
|Principal Investigator:||Ajai Chari, MD||Icahn School of Medicine at Mount Sinai|