Clinical Trial: Ruxolitinib Phosphate in Treating Patients With Chronic Neutrophilic Leukemia or Atypical Chronic Myeloid Leukemia

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

Official Title: Prospective Evaluation of Ruxolitinib Efficacy for CNL/aCML Patients With Mutation of CSF3R

Brief Summary: This phase II trial studies how well ruxolitinib phosphate works in treating patients with chronic neutrophilic leukemia (CNL) or atypical chronic myeloid leukemia (aCML). Ruxolitinib phosphate may stop the growth of cancer cells by blocking some of the enzymes needed for cells to reproduce. This trial also studies the genetic makeup of patients. Certain genes in cancer cells may determine how the cancer grows or spreads and how it may respond to different drugs. Studying how the genes associated with CNL and aCML respond to the study drug may help doctors learn more about CNL and aCML and improve the treatment for these diseases.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the proportion of patients with chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) who have a hematologic response to ruxolitinib (ruxolitinib phosphate) (partial response [PR], complete response [CR], complete response, partial [CRp]).

SECONDARY OBJECTIVES:

I. To determine the frequency of grade 3 or 4 hematologic and non-hematologic adverse events experienced by subjects during therapy with ruxolitinib.

II. To determine whether hematologic responses correlate with certain types of mutations in colony stimulating factor 3 receptor (CSF3R) and reduction in mutant CSF3R allele burden in the peripheral blood.

III. To determine the maximum clinical responses for each subject and the median duration of maximum clinical responses.

IV. To determine the mean % reduction of spleen size, estimated by volume using the conventional prolate ellipsoid method as measured by ultrasound compare to baseline.

V. To determine the mean % reduction of total symptom score as measured by a modified Myeloproliferative Neoplasm Symptom Assessment Form version 2.0 (MPN-SAF) compared to start of study (day 1, cycle 1).

VI. To determine overall survival in subjects who complete a minimum of 1 dose of study drug.

VII. To determine the proportion of subjects who discontinue after completion of > 3 cycles but < 6 cycles.

VIII. To determine the proportion of subjects who discontinue prior to
Sponsor: OHSU Knight Cancer Institute

Current Primary Outcome: Proportion of patients with a hematologic response (partial response, complete response, complete response, partial) [ Time Frame: Up to 2 weeks after last dose of ruxolitinib phosphate ]

A subject is defined as being responsive if he or she has achieved partial response, complete response, or complete response, partial. Proportions with 95% exact confidence intervals will be computed. Chi-square tests will be used to assess the association between hematologic response and mutant CSF3R type, and >= 50% reduction mutant CSF3R allele burden.


Original Primary Outcome: Proportion of patients with a hematologic response (PR, CR, CRp) [ Time Frame: Up to 2 weeks after last dose of ruxolitinib phosphate ]

Proportions with 95% exact confidence intervals will be computed. Chi-square tests will be used to assess the association between hematologic response and mutant CSF3R type, and >= 50% reduction mutant CSF3R allele burden.


Current Secondary Outcome:

  • Change in spleen size, evaluated by ultrasound [ Time Frame: Baseline to day 1 of course 7 ]
    Summary statistics (mean, standard deviation, median, interquartile range) will be reported. Spleen volume will be calculated by the conventional prolate ellipsoid method. Measure spleen width, thickness and maximum length in centimeters. Multiply width by thickness by max length by 0.524 to get the total spleen volume in cm^3.
  • Change in symptom score as measured by a modified myeloproliferative neoplasm symptom assessment form [ Time Frame: Baseline to day 1 of course 7 ]
    Summary statistics (mean, standard deviation, median, interquartile range) will be reported.
  • Duration of maximum clinical responses [ Time Frame: Up to 6 weeks after last dose of ruxolitinib phosphate ]
    Summary statistics (mean, standard deviation, median, interquartile range) will be reported.
  • Incidence of any grade III or IV adverse events or any effects/toxicities directly attributed to study drug requiring permanent cessation of drug [ Time Frame: Up to 6 weeks after last dose of ruxolitinib phosphate ]
    The frequency, duration, and severity of all adverse events will be assessed.
  • Incidence of any hematologic grade III or IV adverse events for thrombocytopenia, anemia, and neutropenia [ Time Frame: Up to 6 weeks after last dose of ruxolitinib phosphate ]
    The frequency, duration, and severity of all adverse events will be assessed.
  • Indicator variable for drop-off [ Time Frame: At 8 weeks ]
  • Indicator variable for drop-off [ Time Frame: Between course 3 and course 6 ]
  • Indicator variable for drop-off since treatment [ Time Frame: Up to 96 weeks ]
  • Indicator variable for reaching course 7 [ Time Frame: Day 1 of course 7 ]
  • Indicator variable for the time of drop-off since treatment [ Time Frame: Up to 96 weeks ]
  • Indicator variable for whether a patient has achieved clinical response of partial response or better [ Time Frame: Day 1 of course 7 ]
    Used to compute the proportion of such patients among all patients who carry a mutant CSF3R and have a more than 25% reduction in mutant CSF3R allele burden with ruxolitinib phosphate therapy compare to start of study (day 1, cycle 1).
  • Maximum clinical responses [ Time Frame: Up to 6 weeks after last dose of ruxolitinib phosphate ]
  • Overall survival in patients who complete at least 6 courses [ Time Frame: Up to 5 years after enrollment in the study ]
    Kaplan-Meier methods will be used to illustrate and summarize overall survival in subjects who complete the study.
  • Proportion of patients with new onset of grade III or higher hemorrhage, as measured by Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: Up to 6 weeks after last dose of ruxolitinib phosphate ]
    Tabulated with summary statistics. The hazard functions of time to onset will be estimated using life table method.
  • Proportion of patients with new onset of grade IV thrombocytopenia events, as measured by Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: Up to 6 weeks after last dose of ruxolitinib phosphate ]
    Tabulated with summary statistics. The hazard functions of time to onset will be estimated using life table method.


Original Secondary Outcome:

  • Incidence of any hematologic grade III or IV adverse events for thrombocytopenia, anemia, and neutropenia [ Time Frame: Up to 6 weeks after last dose of ruxolitinib phosphate ]
    The frequency, duration, and severity of all adverse events will be assessed.
  • Incidence of any grade III or IV adverse events or any effects/toxicities directly attributed to study drug requiring permanent cessation of drug [ Time Frame: Up to 6 weeks after last dose of ruxolitinib phosphate ]
    The frequency, duration, and severity of all adverse events will be assessed.
  • Proportion of patients with new onset of grade IV thrombocytopenia events, as measured by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 [ Time Frame: Up to 6 weeks after last dose of ruxolitinib phosphate ]
    Tabulated with summary statistics. The hazard functions of time to onset will be estimated using life table method.
  • Proportion of patients with new onset of grade III or higher hemorrhage, as measured by CTCAE version 4.03 [ Time Frame: Up to 6 weeks after last dose of ruxolitinib phosphate ]
    Tabulated with summary statistics. The hazard functions of time to onset will be estimated using life table method.
  • Indicator variable for whether a patient has achieved clinical response of PR or better [ Time Frame: Day 1 of course 7 ]
    Used to compute the proportion of such patients among all patients who carry a mutant CSF3R and have a more than 25% reduction in mutant CSF3R allele burden with ruxolitinib phosphate therapy compare to start of study (day 1, cycle 1).
  • Maximum clinical responses [ Time Frame: Up to 6 weeks after last dose of ruxolitinib phosphate ]
  • Duration of maximum clinical responses [ Time Frame: Up to 6 weeks after last dose of ruxolitinib phosphate ]
    Summary statistics (mean, standard deviation, median, interquartile range) will be reported.
  • Change in spleen size, evaluated by ultrasound [ Time Frame: Baseline to day 1 of course 7 ]
    Summary statistics (mean, standard deviation, median, interquartile range) will be reported.
  • Change in symptom score as measured by a modified MPN-SAF [ Time Frame: Baseline to day 1 of course 7 ]
    Summary statistics (mean, standard deviation, median, interquartile range) will be reported.
  • Overall survival in patients who complete at least 6 courses [ Time Frame: Up to 5 years after enrollment in the study ]
    Kaplan-Meier methods will be used to illustrate and summarize overall survival in subjects who complete the study.


Information By: OHSU Knight Cancer Institute

Dates:
Date Received: March 18, 2014
Date Started: May 2014
Date Completion:
Last Updated: May 15, 2017
Last Verified: May 2017