Cyclophosphamide and Pulse Dexamethasone With Rapamycin or Hydroxychloroquine
The purpose of this study is to determine the feasibility of giving (i) rapamycin or (ii) hydroxychloroquine (HCQ), with standard doses of infusional cyclophosphamide and pulse dexamethasone (cy/dex) for patients with relapsed/refractory multiple myeloma, as well as the feasibility of obtaining multiple blood and bone marrow samples during treatment to assess the pharmacodynamic effects of the treatment.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Official Title:||A Pilot Study of Infusional Cyclophosphamide and Pulse Dexamethasone With Rapamycin or Hydroxychloroquine in Patients With Relapsed or Refractory Multiple Myeloma|
- Number of Participants with Adverse Events [ Designated as safety issue: Yes ]The feasibility of administering rapamycin and hydroxychloroquine (HCQ), with standard doses of infusional cyclophosphamide and pulse dexamethasone (cy/dex) for patients with relapsed/refractory multiple myeloma.
- Toxicities and response to the regimen [ Designated as safety issue: Yes ]To demonstrate the feasibility of performing the planned correlative studies to examine mTOR signaling and autophagy activiation and inhibition.
|Study Start Date:||June 2011|
|Study Completion Date:||October 2012|
|Primary Completion Date:||October 2012 (Final data collection date for primary outcome measure)|
Experimental: Hydroxychloroquine (Cohort B)
Infusional cyclophosphamide 300mg/m2/day for 4 days IV and dexamethasone 40mg/day orally or IV for 4 days on days 1 through 4. Hydroxychloroquine oral will be given on days 5 through 28 of cycle 1 and every day of all subsequent cycles (to be given with milk or food at approximately the same time each day)
Dose level 1: 800mg by mouth daily Dose level -1: 600 mg by mouth daily
Experimental: Rapamycin (Cohort A)
Infusional cyclophosphamide 300 mg/m2/day for 4 days IV and dexamethasone 40 mg/day orally or IV for 4 days on days 3 through 6. Rapamycin oral loading dose will be given on day 1 followed by an oral daily dose for an additional 5 days (days 2 through 6) to be given on an empty stomach at approximately the same time each day suggested 11 am)This dosing schedule is the same for all cycles.
Dose level 1: Loading dose 12mg, daily dose 4mg Dose level -1: Loading dose 9mg,daily dose 3mg
Multiple myeloma is a plasma cell neoplasm with median survival of 3 to 5 years. Recent advances have improved patient outlook, but the disease remains incurable and patients become refractory to treatments, develop organ dysfunction from myeloma itself, and encounter severe toxicities from therapies, limiting further treatment options. Subjects over the age of 18 with relapsed or refractory multiple myeloma who have had at least one prior therapy, have a life expectancy of at least 4 weeks and an ECOG performance status of 0,1 or 2 will be included. The investigators propose an initial pilot trial to test the feasibility of giving standard chemotherapy with infusional cyclophosphamide and pulse dexamethasone (cy/dex) for four days, together with the investigational agents, oral rapamycin (cohort A), and in a separate parallel arm, oral hydroxychloroquine (HCQ) (cohort B). The investigators will enroll 3 patients on cohort A and 3 patients on cohort B, both at the planned 1st dose level for the overall phase I/II trial which will succeed this trial if feasibility is demonstrated. The 6 patients from this pilot trial will be included in total number of patients for the overall study which will be completed when further funding is secured. Feasibility will be defined by the ability to deliver the regimen as planned and the ability to perform the planned correlative studies. Subjects will receive up to 12 cycles and will be followed for 12 months after the last cycle. Data collected will include toxicity, response rates, correlative studies to examine the pharmacodynamics of mTOR inhibition and autophagy and the pharmacokinetics of rapamycin and HCQ.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01396200
|United States, Pennsylvania|
|Abramson Cancer Center of the University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Dan Vogl, MD||Abramson Cancer Center of the University of Pennsylvania|