Clinical Trials /

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

NCT02092324

Description:

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.

Related Conditions:
  • Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
  • Chronic Neutrophilic Leukemia
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ruxolitinib Phosphate in Treating Patients With Chronic Neutrophilic Leukemia or Atypical Chronic Myeloid Leukemia
  • Official Title: Prospective Evaluation of Ruxolitinib Efficacy for CNL/aCML Patients With Mutation of CSF3R

Clinical Trial IDs

  • ORG STUDY ID: IRB00010262
  • SECONDARY ID: NCI-2014-00633
  • SECONDARY ID: 10262
  • SECONDARY ID: IRB00010262
  • SECONDARY ID: P30CA069533
  • NCT ID: NCT02092324

Conditions

  • Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
  • Chronic Neutrophilic Leukemia

Interventions

DrugSynonymsArms
Ruxolitinib PhosphateINCB-18424 Phosphate, JakafiTreatment (ruxolitinib phosphate)

Purpose

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 Description

      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 completion of cycle 3.

      OUTLINE:

      Patients receive ruxolitinib phosphate orally (PO) every other day, once daily (QD), or twice
      daily (BID) on days 1-28. Each patient will be followed for a maximum of 96 weeks (24 cycles,
      1 cycle is 4 weeks long). If the study drug continues to be effective, the patient may be
      eligible to continue on study drug past 24 cycles.

      After completion of study treatment, patients are followed up within 2 weeks and at 4-6
      weeks.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (ruxolitinib phosphate)ExperimentalPatients receive ruxolitinib phosphate PO every other day, QD, or BID on days 1-28. Each patient will be followed for a maximum of 96 weeks (24 cycles, 1 cycle is 4 weeks long). If the study drug continues to be effective, the patient may be eligible to continue on study drug past 24 cycles.
  • Ruxolitinib Phosphate

Eligibility Criteria

        Inclusion Criteria:

          -  Subjects must be newly diagnosed or previously diagnosed with CNL or aCML; all
             patients must have a bone marrow biopsy completed during the screening or baseline
             period if one has not been done within 90 days of day 1, cycle one

          -  Subjects must have platelet count greater than 25,000 per microliter at baseline and
             at the start of study (day 1, cycle 1) visit

          -  Subjects must be able to discontinue any drug treatment aimed at lowering disease
             burden in CNL or aCML; subjects should discontinue hydroxyurea to treat underlying CNL
             or aCML disease no later than day -7 (one week before starting ruxolitinib); for drugs
             that have more long-lasting effects on the marrow, such as thalidomide and its
             analogs, and interferon, subjects should discontinue these no later than day -28

          -  Subjects must be willing to accept/continue transfusions to treat low hemoglobin
             levels

          -  Subjects must have a life expectancy of > 6 months

        Exclusion Criteria:

          -  Subjects unable to review and sign informed consent form

          -  Females who are pregnant or breastfeeding, and males and females who cannot comply
             with requirements to avoid fathering a child or becoming pregnant

          -  Subjects with known diagnosis of human immunodeficiency virus (HIV) or chronic active
             Hepatitis B or C; viral testing is not required; subjects with a history of Hepatitis
             B and/or C are allowed on trial if the virus is undetected at the time of enrollment

          -  Subjects with inadequate liver (alanine aminotransferase [ALT]/serum glutamate
             pyruvate transaminase [SGPT] above 4 X upper limit of normal [ULN] or direct bilirubin
             4 X ULN AND the lab abnormalities are felt to be due to underlying liver dysfunction)

          -  Subjects with end stage renal function (creatinine clearance [CrCl] < 15 mL/min or
             glomerular filtration rate [GFR] <15 mL/min) regardless of whether hemodialysis is
             required

          -  Subjects with clinically serious infections requiring ongoing antibiotic therapy

          -  Subjects with severe (immediately life threatening) and recent (occurring within the
             last 3 months) cardiac dysfunction, pulmonary dysfunction, esophageal variceal
             bleeding, hemorrhagic strokes, or intracranial hemorrhage are not eligible for study
             participation

          -  Subjects requiring therapeutic doses of anticoagulation or anti-platelet therapies
             (aspirin above 81 mg daily, Plavix or similar agents) AND platelet counts are below
             50,000 on two different laboratory evaluations, separated by minimum of two weeks

          -  Taking investigational or commercial agents or therapies with the intent to treat the
             subject's malignancy other than those therapies permitted

          -  Subjects with invasive malignancy over the previous 2 years except treated early stage
             carcinomas of the skin, completely resected intraepithelial carcinoma of the cervix,
             and completely resected papillary thyroid and follicular thyroid cancers

          -  Previous allergic reactions to janus kinase (JAK) inhibitors or excipients

          -  Prior therapy with ruxolitinib or other JAK inhibitors

          -  Subjects who have had major surgery within 4 weeks prior to entering the study

          -  Subjects who are anticipated to receive a transplant within the first 6 months of
             treatment on trial
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:The frequency, duration, and severity of all adverse events will be assessed.
Measure: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
Safety Issue:
Description:The frequency, duration, and severity of all adverse events will be assessed.
Measure: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
Safety Issue:
Description:Tabulated with summary statistics. The hazard functions of time to onset will be estimated using life table method.
Measure: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
Safety Issue:
Description:Tabulated with summary statistics. The hazard functions of time to onset will be estimated using life table method.
Measure:Indicator variable for whether a patient has achieved clinical response of partial response or better
Time Frame:Day 1 of course 7
Safety Issue:
Description: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).
Measure:Indicator variable for drop-off since treatment
Time Frame:Up to 96 weeks. If the study drug continues to be effective, the patient may be eligible to continue on study drug past 24 cycles.
Safety Issue:
Description:
Measure:Indicator variable for the time of drop-off since treatment
Time Frame:Up to 96 weeks. If the study drug continues to be effective, the patient may be eligible to continue on study drug past 24 cycles.
Safety Issue:
Description:
Measure:Indicator variable for drop-off
Time Frame:At 8 weeks
Safety Issue:
Description:
Measure:Indicator variable for drop-off
Time Frame:Between course 3 and course 6
Safety Issue:
Description:
Measure:Indicator variable for reaching course 7
Time Frame:Day 1 of course 7
Safety Issue:
Description:
Measure:Maximum clinical responses
Time Frame:Up to 6 weeks after last dose of ruxolitinib phosphate
Safety Issue:
Description:
Measure:Duration of maximum clinical responses
Time Frame:Up to 6 weeks after last dose of ruxolitinib phosphate
Safety Issue:
Description:Summary statistics (mean, standard deviation, median, interquartile range) will be reported.
Measure:Change in spleen size, evaluated by ultrasound
Time Frame:Baseline to day 1 of course 7
Safety Issue:
Description: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.
Measure:Change in symptom score as measured by a modified myeloproliferative neoplasm symptom assessment form
Time Frame:Baseline to day 1 of course 7
Safety Issue:
Description:Summary statistics (mean, standard deviation, median, interquartile range) will be reported.
Measure:Overall survival in patients who complete at least 6 courses
Time Frame:Up to 5 years after enrollment in the study
Safety Issue:
Description:Kaplan-Meier methods will be used to illustrate and summarize overall survival in subjects who complete the study.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:OHSU Knight Cancer Institute

Last Updated

June 4, 2018