A Phase I/II Trial Of Very Low to Low-Doses of Continuous Azacitidine in Combination With Standard Doses of Lenalidomide and Low-Dose Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
Phase I: Define the highest tolerated low dose (HTLD) and safety of azacitidine given at low
but increasing doses up to 50mg/m2 twice a week concurrently with standard dose lenalidomide
and low dose dexamethasone in patients with relapsed or refractory multiple myeloma.
Phase II: Response according to international response criteria (>= PR) and clinical benefit
response (>= minor response according to adapted EBMT (European Group for Blood and Marrow
Transplantation) criteria). PR=partial response
- Correlate response with plasma activity of the azacitidine inactivating enzyme cytidine
- Progression-free survival and overall survival
- Peripheral blood hematopoietic progenitor (CD34+) yield and time to neutrophil and
platelet recovery in patients undergoing autologous stem cell transplantation
- Promoter demethylation and gene reactivation in myeloma cells and hematopoietic
progenitors treated at the HTLD level after cycle 1
- Changes in global gene expression in myeloma cells treated at the HTLD level after
This is a phase I, dose-escalation study of azacitidine followed by a phase II study.
Patients receive azacitidine subcutaneously once or twice weekly and oral dexamethasone once
weekly starting on day 1. Patients also receive oral lenalidomide once daily on days 1-21.
Treatment repeats every 28 days for 6 courses. Patients then continue to receive
lenalidomide as maintenance therapy. Treatment continues in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 3 years.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Phase I: Highest tolerated low dose (HTLD)
azacitidine given at low but increasing doses up to 50mg/m2 twice a week
during the first 28-day cycle
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
United States: Institutional Review Board
|Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center||Cleveland, Ohio 44106-5065|
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center||Cleveland, Ohio 44195|