NCT01155583

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

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

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 45 (actual)
• Sponsor: Case Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

PRIMARY OBJECTIVES: 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 Glomerular filtration rate (GFR)-adjusted lenalidomide and low dose dexamethasone in patients with relapsed or refractory multiple myeloma. SECONDARY OBJECTIVES: * Response according to international response criteria (≥PR) and clinical benefit response (≥minor response according to adapted EBMT criteria) * Correlate response with plasma activity of the azacitidine inactivating enzyme cytidine deaminase (CDA) * 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 / HTLD-CKD level after cycle 1 * Changes in global gene expression in myeloma cells treated at the HTLD / HTLD-CKD level after cycle 1 OUTLINE: 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.

Conditions

• Refractory Multiple Myeloma

Interventions

Type	Name	Description
DRUG	azacitidine	Given by subcutaneous injection (SC)
DRUG	lenalidomide	Given orally
DRUG	dexamethasone	Given orally
OTHER	DNA methylation analysis	Correlative studies
OTHER	gene expression analysis	Correlative studies
OTHER	bone marrow aspiration	Correlative studies
OTHER	immunohistochemistry staining method	Correlative studies
OTHER	reverse transcriptase-polymerase chain reaction	Correlative studies
OTHER	flow cytometry	Correlative studies

Timeline

• Start date: 2010-06-01
• Primary completion: 2016-05-28
• Completion: 2018-11-06
• First posted: 2010-07-02
• Last updated: 2020-11-16
• Results posted: 2020-10-12

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study