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NCT01155583: Phase 1/2: Low-Dose Azacitidine, Lenalidomide & Low-Dose Dexamethasone in RRMM Myeloma

NCT01155583: Phase 1/2: Low-Dose Azacitidine, Lenalidomide, and Low-Dose Dexamethasone in Relapsed or Refractory Multiple Myeloma


Azacitidine-Rd

Low-Dose Azacitidine, Lenalidomide, and Low-Dose Dexamethasone in Relapsed or Refractory Multiple Myeloma


RATIONALE: Drugs used in chemotherapy, such as azacitidine and dexamethasone, work in different ways to stop the growth of cancer cells either by killing the cells or by stopping them from dividing. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Giving azacitidine together with lenalidomide and dexamethasone may kill more cancer cells.


PURPOSE: This phase I/II trial is studying the side effects and best dose of azacitidine when given together with lenalidomide and low-dose dexamethasone in treating patients with relapsed or refractory multiple myeloma.


Sponsor:

Case Comprehensive Cancer Center


Location:

United States, Ohio

 

ClinicalTrials.gov Identifier: NCT01155583


Official Title: 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

First Posted : July 2, 2010


Click here for details on Clinicaltrials.gov

 

Drug: azacitidine

Drug: lenalidomide

Drug: dexamethasone

Other: DNA methylation analysis

Other: gene expression analysis

Other: bone marrow aspiration

Other: immunohistochemistry staining method

Other: reverse transcriptase-polymerase chain reaction

Other: flow cytometry

 

A phase I/II trial of very low to low-dose continuous azacitidine in combination with standard doses of lenalidomide and low-dose dexamethasone in patients with relapsed or refractory multiple myeloma.

Meeting Abstract | 2015 ASCO Annual Meeting I


Conclusions: AZA was well tolerated up to target 50mg/m2 SC twice a week in combination with len-dex . Inverse correlation of CDA activity with response suggests AZA contributed to benefit and supports development of the HPLC assay to select patients for aza nucleoside treatment and guide development of CDA inhibitors.


 

MYELOMA - THERAPY, EXCLUDING TRANSPLANTATION| NOVEMBER 16, 2012

Very Low to Low Doses of Continuous Azacitidine in Combination with Standard Doses of Lenalidomide and Low-Dose Dexamethasone (Rd) in Patients with Relapsed or Refractory Multiple Myeloma (RRMM): Interim Results of a Phase I/II Study

Conclusions:

Azacitidine was generally well tolerated up to the target maximal dose of 50mg/m2SC twice a week (BIW) in combination with Rd given to 4 out of 6 patients required for establishing the phase 2 dose. Encouraging response rates in refractory MM correlated with low plasma activity of the azacitidine inactivating enzyme CDA found predominantly in women. Results support development of azacitidine in RRMM and argue for testing combination with the competitive inhibitor of CDA, tetrahydrouridine. Until then, dose escalation in non-responding but tolerating patients will be explored.




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