Clinical Trial: Ibrutinib and Azacitidine for Treatment of Higher Risk Myelodysplastic Syndrome

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: 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 Refus

Brief 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 Summary:

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 mo
Sponsor: University of California, Davis

Current Primary Outcome: Incidence of toxicity of ibrutinib and azacitidine, graded according to the Common Terminology Criteria for Adverse Events [ Time Frame: Within 30 days following the last dose of study drug or the first date starting new anticancer therapy ]

For each adverse event, the percentage of subjects who experience at least 1 occurrence of the given event will be summarized.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Disease Free Survival [ Time Frame: From the time of first documented Complete Response until relapse or the date of death from any cause, assessed up to 6 months post-treatment ]
    For subjects achieving a Complete Response, Disease Free Survival will be calculated to determine durability of response. Descriptive statistics will be used, including mean, standard deviation, median, and minimum and maximum values for continuous variables and frequencies and percentages for categorical variables. Time-to-event data will be summarized descriptively by life-table statistics (median time to event; Kaplan-Meier plots).
  • Disease response per modified International Working Group (IWG) 2006 response criteria for MDS [ Time Frame: Up to 96 weeks ]
    Descriptive statistics will be used, including mean, standard deviation, median, and minimum and maximum values for continuous variables and frequencies and percentages for categorical variables.
  • HNR, defined as the proportion of treated subjects who achieve a CR, PR or HI as best response as assessed by the investigator and as defined by the modified IWG 2006 response criteria for MDS [ Time Frame: Up to 96 weeks ]
    Descriptive statistics will be used, including mean, standard deviation, median, and minimum and maximum values for continuous variables and frequencies and percentages for categorical variables.
  • Overall survival [ Time Frame: From the time of first study drug administration until the date of death from any cause, assessed up to 6 months post-treatment ]
    Descriptive statistics will be used, including mean, standard deviation, median, and minimum and maximum values for continuous variables and frequencies and percentages for categorical variables. Time-to-event data will be summarized descriptively by life-table statistics (median time to event; Kaplan-Meier plots).
  • Progression Free Survival [ Time Frame: From the time of first study drug administration until the date of progression or death from any cause, assessed up to 6 months post-treatment ]
    Descriptive statistics will be used, including mean, standard deviation, median, and minimum and maximum values for continuous variables and frequencies and percentages for categorical variables. Time-to-event data will be summarized descriptively by life-table statistics (median time to event; Kaplan-Meier plots).


Original Secondary Outcome: Same as current

Information By: University of California, Davis

Dates:
Date Received: July 27, 2015
Date Started: April 2016
Date Completion: November 2019
Last Updated: December 20, 2016
Last Verified: December 2016