Cyclophosphamide(Cy)/ Dexamethasone(Dex)/Rapamycin (Rapa)/Hydroxychloroquine (HCQ) for Relapsed or Refractory Myeloma(Rel/Ref MM)
Multiple myeloma (MM) is a type of cancer with an average survival of 3 to 5 years. The disease remains incurable and patients become unresponsive to treatments. Patients also develop organ problems and can have severe side effects from therapy. All of these factors limit treatment options. This protocol will enroll subjects who have MM that has returned after treatment or has stopped responding to treatment. The purpose of this study is to test the safety of rapamycin and hydroxychloroquine (study drugs) at different dose levels. The investigators want to find out what effects, good and/or bad, it has on MM. The study drugs have not been approved by the U.S. Food and Drug Administration (FDA) or any other regulatory agency for general use in this type of cancer and their benefits and side effects are not fully known. These study drugs will be given with standard chemotherapy, cyclophosphamide and dexamethasone, which have both been approved by the FDA for use in this disease. The investigators believe that the combination of standard chemotherapy, with rapamycin and hydroxychloroquine (HCQ), may improve the response outcome compared to standard chemotherapy alone. The investigators think that both study drugs will improve the sensitivity of the myeloma cells in the body to standard chemotherapy, making it easier for the chemotherapy to kill or damage the myeloma cells. However, this combination has never been tried in patients before. In future research studies, the investigators hope to determine how well this drug combination will work in fighting and killing myeloma cells.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||Phase I Infusional Cyclophosphamide and Pulse Dexamethasone With Rapamycin and Hydroxychloroquine in Patients With Relapsed or Refactory Myeloma|
- Maximum tolerated dose (MTD)of Hydroxychloroquine (HCQ),Rapamycin, Dexamethasone, and Cyclophosphamide. [ Time Frame: Duration of the study; up to 2 years ] [ Designated as safety issue: Yes ]To determine the maximum tolerated dose (MTD) of hydroxychloroquine (HCQ) in combination with rapamycin and infusional cyclophosphamide and pulse dexamethasone (cy/dex) for patients with relapsed/ refractory multiple myeloma.
- Evaluation of biological activity [ Time Frame: Duration of the study; Up to 2 years ] [ Designated as safety issue: Yes ]To evaluate biological activity of the combination of cyclophosphamide, dexamethasone, rapamycin and hydroxychloroquine in patients with relapsed/ refractory multiple myeloma.
- Evaluation of efficacy [ Time Frame: Duration of the study; up to 2 years ] [ Designated as safety issue: No ]To evaluate efficacy of the combination of cyclophosphamide, dexamethasone, rapamycin and hydroxychloroquine in patients with relapsed/ refractory multiple myeloma.
|Study Start Date:||December 2012|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Hydroxychloroquine (HCQ) oral will begin on day 5 of cycle 1 and daily thereafter. It will be given every day of all subsequent cycles (to be given with milk or food at approximately the same time each day, suggested with dinner at 4-6pm).
starting dose of HCQ (dose level 1) will be 400mg escalating as follows: 600mg, 800mg, on to the highest dose of 1200mg daily (dose level 4).
Rapamycin loading dose on day -2 of each cycle, followed by a daily dose on days -1 through 4 (on an empty stomach at approximately the same time every day- suggested at 2pm).
4mg rapamycin daily with 12mg loading dose
|Drug: Hydroxychloroquine Drug: Rapamycin|
|United States, Oregon|
|OHSU Knight Cancer Institute||Recruiting|
|Portland, Oregon, United States, 97239|
|Contact: Amy Bedford email@example.com|
|Principal Investigator: Emma Scott, M.D.|