Status and phase
Conditions
Treatments
About
The purpose of this study is to determine the safety and activity of the investigational drug known as carfilzomib in the treatment of multiple myeloma (MM) when it is given at doses above the usual dose after the standard dosing has become ineffective. The other purpose of this study is to understand what causes the multiple myeloma to become resistant to carfilzomib and whether this can be overcome in the laboratory.
Full description
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.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Disease-related:
Multiple myeloma
Subjects must have measurable disease, defined as one or both of the following:
Refractory to the most recently received therapy. Refractory disease is defined as ≤ 25% response or progression during therapy or within 60 days after completion of therapy.
Subjects must have progressed on standard dose 20/27 mg/m2 and schedule of carfilzomib without having had any carfilzomib related grade 3 or 4 toxicities.
Subjects must have received ≥ 2 prior regimens for relapsed disease. Induction therapy and stem cell transplant will be considered as one regimen
Subjects must have received prior treatment with bortezomib, and either thalidomide or lenalidomide
Subjects must have received an alkylating agent unless contraindicated. Subjects may have received these agents alone or in combination with other myeloma treatments.
Demographic:
Laboratory/Radiology
Exclusion criteria
Disease-related
Concurrent Conditions
Primary purpose
Allocation
Interventional model
Masking
13 participants in 1 patient group
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal