NCT01396200

Cyclophosphamide and Pulse Dexamethasone With Rapamycin or Hydroxychloroquine

A Pilot Study of Infusional Cyclophosphamide and Pulse Dexamethasone With Rapamycin or Hydroxychloroquine in Patients With Relapsed or Refractory Multiple Myeloma

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 6 (estimated)
• Sponsor: Abramson Cancer Center at Penn Medicine · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Myeloma

Interventions

Type	Name	Description
DRUG	Hydroxychloroquine	Dose level 1: 800mg by mouth daily Dose level -1: 600 mg by mouth daily
DRUG	Rapamycin	Dose level 1: Loading dose 12mg, daily dose 4mg Dose level -1: Loading dose 9mg,daily dose 3mg

Timeline

• Start date: 2011-06-01
• Primary completion: 2012-10-01
• Completion: 2012-10-01
• First posted: 2011-07-18
• Last updated: 2013-02-26

Locations

1 site across 1 country: United States