An Open-Label Phase I Study of the Safety and Efficacy of Bortezomib in Combination With CC-5013 in the Treatment of Subjects With Relapsed and Relapsed/Refractory Multiple Myeloma
- Within 21 days of starting treatment the following tests will be performed: physical
exam (including vital signs), ECG, neurological examination, blood tests, urine tests,
bone marrow aspiration, x-rays and MRI or CT scan.
- Patients will receive bortezomib intravenously on day 1,4,8 and 11 followed by 10 days
of rest. CC-5013 will be given orally on days 1-14 followed by 7-dyas of rest. One
cycle lasts 21 days. This study will evaluate different dose levels of bortezomib and
CC-5013 to see which dose level seems to be the best for most people. There will be 8
- Patients will be assigned to a dose level depending upon when they begin the study and
how other dose levels have been tolerated by patients that are already on the study.
Three to six patients will be treated at each dose level and will be observed for one
full cycle. Depending upon the side effects, the dose level will increase, stay the
same or be decreased by one level for the next group. 10 additional patients will be
treated at the dose that is thought the best.
- On day four of the treatment cycle blood tests, vital signs and a review of side
effects will be performed.
- On day eight of the the treatment cycle blood tests, vital signs, review of side
effects and an ECG will be performed prior to medication administration. A bortezomib
level will be taken before bortezomib infusion, 15 minutes, 1/2 hour, 45 minutes, 1
hour, 2 hours, 4 hours, 6 hours, 8 hours and 12 hours after the dose. Additional blood
levels will be collected 24, 48, and 72 hours after the dose. (These blood levels will
done during the first cycle only).
- On day 11 and day 14 of the treatment cycle blood tests, vital signs and review of side
effects will be performed.
- After 2 cycles of treatment, the doctor will assess how the patient's disease is
responding to the treatment. Additional tests such as bone marrow biopsy, x-rays or
scans may be performed. If the disease is stable or getting better, patients will
continue to receive repeated cycles of treatment. If the disease is getting worse,
dexamethasone may be added to the treatment cycle.
- If dexamethasone is added, the dosing will start on days 1,2,4,5,8,9 and 11 of the
21-day cycle. The disease will then be reassessed after 2 additional cycles. If the
disease is getting worse, the patient will be removed from the study.
- Once 8 cycles of treatment have been performed, the disease will be fully assessed
again by blood tests, bone marrow biopsy, x-rays or scans. Again, if it is determined
that the disease is stable of getting better, additional treatment cycles can be
performed. If the disease is getting worse, treatment will be stopped..
- A follow-up visit will be scheduled one month after the last dose of the study drug and
will include: physical exam, vital signs, neurological examination, and review of
- Patients will remain on this study as long as the side effects are not too severe and
the disease has not progressed.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To evaluate the safety of bortezomib when given in combination with CC-6=5013 and to identify the maximum tolerated dose as well as a recommended Phase II dose in subjects with refractory and relapsed multiple myeloma.
Paul Richardson, MD
Dana-Farber Cancer Institute
United States: Food and Drug Administration
|University of Michigan||Ann Arbor, Michigan 48109-0624|
|Beth Israel Deaconess Medical Center||Boston, Massachusetts 02215|
|Winship Cancer Center||Atlanta, Georgia 30322|
|St. Vincent's Comprehensive Cancer Center||New York, New York 10011|
|H. Lee Moffitt Cancer Center||Tampa, Florida 33612|
|Dana-Farber Cancer Center||Boston, Massachusetts 02115|