NCT02553941

Ibrutinib and Azacitidine for Treatment of Higher Risk Myelodysplastic Syndrome

Phase 1b Trial of the Combination of Ibrutinib and Azacitidine for the Treatment of Higher Risk Myelodysplastic Syndromes in Previously Treated Patients or in Untreated Patients Unfit for or Who Refuse Intense Therapy

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 21 (actual)
• Sponsor: Brian Jonas · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase Ib trial studies the side effects and best dose of ibrutinib when given together with azacitidine in treating patients with myelodysplastic syndrome that is likely to occur or spread (higher risk) and who were previously treated or untreated and unfit for or refused intense therapy. Ibrutinib and azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of ibrutinib in combination with azacitidine in patients with higher risk myelodysplastic syndrome (MDS) and to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose of ibrutinib combined with azacitidine. SECONDARY OBJECTIVES: I. To do an early assessment of the efficacy of the combination of ibrutinib and azacitidine in higher risk MDS. Specific secondary endpoints include: disease response per modified International Working Group (IWG) 2006 response criteria for MDS, hematologic normalization rate (HNR = complete remission \[CR\] + partial remission \[PR\] + hematologic improvement \[HI\]), overall survival (OS), progression free survival (PFS), disease free survival (DFS), and time to response (TTR). TERTIARY OBJECTIVES: I. To evaluate the pharmacodynamic and biological effects and impact of quality of life (QoL) of the combination of ibrutinib and azacitidine in patients with higher risk MDS is the exploratory objective of this study. Exploratory endpoints include: laboratory biomarker analysis and effect on QoL assessments. OUTLINE: This is a dose-escalation study of ibrutinib. Patients receive azacitidine intravenously (IV) over 10-40 minutes or subcutaneously (SC) once daily (QD) on days 1-7 or 1-5 and 8-9, and ibrutinib orally (PO) QD on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 6 months.

Conditions

• Chronic Myelomonocytic Leukemia
• de Novo Myelodysplastic Syndrome
• Previously Treated Myelodysplastic Syndrome
• Refractory Anemia With Excess Blasts in Transformation
• Secondary Myelodysplastic Syndrome

Interventions

Type	Name	Description
DRUG	Azacitidine	Given intravenous or subcutaneous
DRUG	Ibrutinib	Given by mouth once daily

Timeline

• Start date: 2016-05-17
• Primary completion: 2019-05-25
• Completion: 2019-11-07
• First posted: 2015-09-18
• Last updated: 2022-10-06

Locations

5 sites across 1 country: United States