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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02092324
Recruitment Status : Completed
First Posted : March 20, 2014
Results First Posted : November 16, 2020
Last Update Posted : November 16, 2020
Sponsor:
Information provided by (Responsible Party):
Kim-Hien Dao, OHSU Knight Cancer Institute

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
Chronic Neutrophilic Leukemia
Interventions Other: Laboratory Biomarker Analysis
Other: Quality-of-Life Assessment
Other: Questionnaire Administration
Drug: Ruxolitinib Phosphate
Enrollment 51
Recruitment Details The first patient was enrolled July 8, 2014 and recruitment ended in September 2019, across seven medical centers in the US.
Pre-assignment Details Two subjects who were enrolled were shortly determined to be misdiagnosed and were not evaluable bringing the total eligible subjects to 49. An additional subject was not evaluable for the primary endpoint because of missing bone marrow (BM) biopsy data.
Arm/Group Title Treatment (Ruxolitinib Phosphate)
Hide Arm/Group Description Patients receive ruxolitinib phosphate PO every other day (QOD), or twice a day (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.
Period Title: Overall Study
Started 51
End of Cycle 6 [1] 25 [2]
Wildtype CSF3R [3] 23
Mutant CSF3R [3] 26
Completed 32
Not Completed 19
Reason Not Completed
Adverse Event             1
Lack of Efficacy             6
Proceed to Transplant             3
Physician Decision             7
Misdiagnosis             2
[1]
We expanded accrual to enroll additional evaluable subjects for analysis of the secondary endpoints.
[2]
This study has an accrual goal of 25 evaluable subjects who reach cycle 7, week 1.
[3]
Participants were stratified by CSF3R mutation status
Arm/Group Title Wildtype CSF3R Mutant CSF3R Total
Hide Arm/Group Description Subjects with wild type granulocyte Colony Stimulating Factor Receptor 3 (CSF3R) Subjects with mutant CSF3R Total of all reporting groups
Overall Number of Baseline Participants 23 26 49
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 23 participants 26 participants 49 participants
72.8
(43.1 to 90.7)
73.0
(60.2 to 92.3)
72.8
(43.1 to 92.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 26 participants 49 participants
Female
8
  34.8%
12
  46.2%
20
  40.8%
Male
15
  65.2%
14
  53.8%
29
  59.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 26 participants 49 participants
White
21
  91.3%
26
 100.0%
47
  95.9%
Black or African American
2
   8.7%
0
   0.0%
2
   4.1%
Disease group  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 26 participants 49 participants
CNL
5
  21.7%
17
  65.4%
22
  44.9%
aCML
18
  78.3%
9
  34.6%
27
  55.1%
Splenomegaly at baseline  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 26 participants 49 participants
No Splenomegaly
6
  26.1%
3
  11.5%
9
  18.4%
Splenomegaly
17
  73.9%
23
  88.5%
40
  81.6%
Spleen volume by ultrasound   [1] 
Median (Full Range)
Unit of measure:  Cm^3
Number Analyzed 20 participants 25 participants 45 participants
582.8
(147.4 to 3042.4)
586.9
(96.2 to 2578.6)
586.9
(96.2 to 3042.4)
[1]
Measure Analysis Population Description: Four subjects did not have baseline spleen size evaluated in three-dimensions by ultrasound
Palpable spleen length at left midcostochondral line (LMC)   [1] 
Median (Full Range)
Unit of measure:  Cm
Number Analyzed 15 participants 17 participants 32 participants
9.0
(0.0 to 26.0)
5.0
(0.0 to 18.0)
5.8
(0.0 to 26.0)
[1]
Measure Analysis Population Description: 17 subjects did not have measureable or palpable spleen at baseline
White blood cell count  
Median (Full Range)
Unit of measure:  10^9 cells/L
Number Analyzed 23 participants 26 participants 49 participants
48.1
(8.5 to 256.9)
51.6
(6.6 to 209.0)
50.7
(6.6 to 256.9)
Absolute Neutrophil Count (ANC)  
Median (Full Range)
Unit of measure:  10^9 cells/L
Number Analyzed 23 participants 26 participants 49 participants
35.4
(6.9 to 105.3)
46.0
(6.1 to 200.6)
41.9
(6.1 to 200.6)
Hemoglobin  
Median (Full Range)
Unit of measure:  g/dL
Number Analyzed 23 participants 26 participants 49 participants
11.0
(7.0 to 14.5)
10.4
(6.7 to 13.3)
10.8
(6.7 to 14.5)
Platelets  
Median (Full Range)
Unit of measure:  10^9 cells/L
Number Analyzed 23 participants 26 participants 49 participants
134
(25 to 488)
125
(26 to 423)
130
(25 to 488)
Prior therapy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 26 participants 49 participants
None
10
  43.5%
8
  30.8%
18
  36.7%
Prior therapy
13
  56.5%
18
  69.2%
31
  63.3%
Type of prior therapy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 26 participants 49 participants
Hydroxyurea
11
  47.8%
15
  57.7%
26
  53.1%
Hydroxyurea + Azacitidine
1
   4.3%
0
   0.0%
1
   2.0%
Hydroxyurea + Dasatinib
1
   4.3%
0
   0.0%
1
   2.0%
Decitabine
0
   0.0%
2
   7.7%
2
   4.1%
Other (interferon)
0
   0.0%
1
   3.8%
1
   2.0%
No prior treatment
10
  43.5%
8
  30.8%
18
  36.7%
IPSS total score   [1] 
Median (Full Range)
Unit of measure:  Units on a scale
Number Analyzed 23 participants 26 participants 49 participants
2.0
(1.0 to 5.0)
2.5
(1.0 to 5.0)
2.0
(1.0 to 5.0)
[1]
Measure Description: International Prognostic Scoring System (IPSS), based on three prognostic indicators, with values ranging from 0 - 5 where 0 indicates "Low Risk"; 1 indicates "Intermediate 1 Risk"; 2 indicates "Intermediate 2 Risk"; 3 and above indicate "High Risk".
MPN-SAF TSS   [1] [2] 
Median (Full Range)
Unit of measure:  Units on a scale
Number Analyzed 21 participants 25 participants 46 participants
28.0
(0.0 to 72.0)
20.0
(2.0 to 53.0)
23.5
(0.0 to 72.0)
[1]
Measure Description: Myeloproliferative Neoplasm Symptom Assessment Form Total symptom score (MPN-SAF TSS) ranges from 0 (no symptoms) to 10 (worst imaginable symptoms). The score is a composite of 10 independent measurements, generating a final score ranging from 0 - 100. Although lower scores indicate fewer symptoms, not all symptoms directly relate to outcomes.
[2]
Measure Analysis Population Description: Three subjects failed to respond to all 10 questions required to score TSS
Prestudy disease duration, months  
Median (Full Range)
Unit of measure:  Months
Number Analyzed 23 participants 26 participants 49 participants
0.9
(0.2 to 24.9)
1.2
(0.0 to 64.1)
0.9
(0.0 to 64.1)
1.Primary Outcome
Title Percentage of First 25 Enrolled Patients With a Hematologic Response to Ruxolitinib (Complete Response (CR), Partial Response (PR))
Hide Description A subject is defined as being responsive (responder) if he or she has achieved complete response (CR) or partial response (PR) at the beginning of cycle 7 compared to start of study (day 1,cycle 1). Subjects who do not reach the start of cycle 7 are counted as non-responders. Proportions with 95% exact confidence intervals will be computed. Protocol-defined Response evaluates changes in white blood cell count, absolute neutrophil count, marrow findings and spleen size to define response (attached protocol, Section 10.6, Clinical Response, Table 6 and Table). IWG-defined Response evaluates bone marrow cellularity and myeloblast percent, absence of osteopmyelofibrosis, peripheral blood elements (white blood cell, Neutrophil, Monocyte and platelet counts, hemoglobin density, percent blasts and Neutrophil precursors), symptom resolution, dysplasia, and spleen size to determine response (attached reference).
Time Frame Start of cycle 7
Hide Outcome Measure Data
Hide Analysis Population Description
First 25 enrolled subjects enrolled, received at least one dose of study drug, and were evaluated for protocol-defined and International Working Group (IWG) defined objective response
Arm/Group Title First 25 Enrolled Subjects
Hide Arm/Group Description:
First 25 enrolled subjects evaluated for protocol-defined objective response
Overall Number of Participants Analyzed 25
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Protocol-defined Response
32
(15 to 54)
IWG-defined Response
4
(0.1 to 20)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection First 25 Enrolled Subjects
Comments Proportion estimated using Clopper-Pearson method. P-value is one-sided proportion test for greater than 10% response rate (based on Simon's 2-stage).
Type of Statistical Test Superiority
Comments 1-proportion test for greater than 10% difference.
Statistical Test of Hypothesis P-Value 0.002
Comments p-value for Protocol-defined objective response
Method binomial
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection First 25 Enrolled Subjects
Comments Proportion estimated using Clopper-Pearson method. P-value is one-sided proportion test for greater than 10% response rate (based on Simon's 2-stage).
Type of Statistical Test Superiority
Comments 1-proportion test for greater than 10% difference
Statistical Test of Hypothesis P-Value 0.90
Comments p-value is for IWG-defined objective response
Method binomial
Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participant With Any Hematologic Grade III or IV Adverse Events.
Hide Description The frequency (percentage) of subjects with any hematologic [thrombocytopenia, anemia or neutropenia] grade III or IV adverse events according to CTCAE v4.0
Time Frame Up to 6 weeks after last dose of ruxolitinib phosphate
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects receiving at least one dose of ruxolitinib
Arm/Group Title Treatment (Ruxolitinib Phosphate)
Hide Arm/Group Description:

Patients 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.

Laboratory Biomarker Analysis: Correlative studies

Quality-of-Life Assessment: Ancillary studies

Questionnaire Administration: Ancillary studies

Ruxolitinib Phosphate: Given PO

Overall Number of Participants Analyzed 49
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
46.9
(32.5 to 61.7)
3.Secondary Outcome
Title Percentage of Participants With Any Non-hematologic Grade III or IV Adverse Events.
Hide Description The frequency (percentage) of subjects with any non-hematologic grade III or IV adverse events according to CTCAE v4.0
Time Frame Up to 6 weeks after last dose of ruxolitinib phosphate
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects receiving at least one dose of ruxolitinib
Arm/Group Title Treatment (Ruxolitinib Phosphate)
Hide Arm/Group Description:

Patients 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.

Laboratory Biomarker Analysis: Correlative studies

Quality-of-Life Assessment: Ancillary studies

Questionnaire Administration: Ancillary studies

Ruxolitinib Phosphate: Given PO

Overall Number of Participants Analyzed 49
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
69.4
(54.6 to 81.7)
4.Secondary Outcome
Title Percentage of Participants Who Achieved Clinical Response of Partial Response or Better
Hide Description Compute the percent of patients with protocol-defined objective response (CR+PR) and IWG-defined objective response (CR+PR) at the start of cycle 7 among all enrolled patients (n = 49). Patients who withdrew prior to the end of cycle 6 are considered non-responders. Protocol-defined Response evaluates changes in white blood cell count, absolute neutrophil count, marrow findings and spleen size to define response (attached protocol, Section 10.6, Clinical Response, Table 6 and Table). IWG-defined Response evaluates bone marrow cellularity and myeloblast percent, absence of osteopmyelofibrosis, peripheral blood elements (white blood cell, Neutrophil, Monocyte and platelet counts, hemoglobin density, percent blasts and Neutrophil precursors), symptom resolution, dysplasia, and spleen size to determine response (attached reference).
Time Frame Start of cycle 7
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled subjects who receive at least one dose of ruxolitinib. Subjects who withdraw prior to the start of cycle 7 are considered non-responders.
Arm/Group Title Treatment (Ruxolitinib Phosphate)
Hide Arm/Group Description:

Patients 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.

Laboratory Biomarker Analysis: Correlative studies

Quality-of-Life Assessment: Ancillary studies

Questionnaire Administration: Ancillary studies

Ruxolitinib Phosphate: Given PO

Overall Number of Participants Analyzed 49
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Protocol-defined Response
33
(20 to 48)
IWG-defined Response
8
(2.3 to 20)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment (Ruxolitinib Phosphate)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Proportion estimated using Clopper-Pearson method. P-value is one-sided proportion test for greater than 10% response rate.
Statistical Test of Hypothesis P-Value <0.0001
Comments p-value for protocol-defined objective response. p-value for IWG-defined objective response is 0.70
Method Clopper-Pearson method
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treatment (Ruxolitinib Phosphate)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Proportion estimated using Clopper-Pearson method. P-value is one-sided proportion test for greater than 10% response rate.
Statistical Test of Hypothesis P-Value 0.70
Comments p-value for IWG-defined objective response
Method Clopper-Pearson method
Comments [Not Specified]
5.Secondary Outcome
Title Median Time on Study (Months) for Early Drop Offs
Hide Description Median and range of months on study for subjects who did not complete 6 cycles of Ruxolitinib
Time Frame End of cycle 6
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled subjects who received at least one dose of study drug but did not complete 6 full cycles of Ruxolitinib
Arm/Group Title Treatment (Ruxolitinib Phosphate)
Hide Arm/Group Description:

Patients 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.

Laboratory Biomarker Analysis: Correlative studies

Quality-of-Life Assessment: Ancillary studies

Questionnaire Administration: Ancillary studies

Ruxolitinib Phosphate: Given PO

Overall Number of Participants Analyzed 17
Median (Full Range)
Unit of Measure: months
2.4
(.2 to 5.7)
6.Secondary Outcome
Title Median Time on Study (Months) for All Enrolled Subjects
Hide Description Median and range of months on Ruxolitinib for all enrolled subjects
Time Frame Outcome is measured from the first dose of study drug. If study drug continues to be effective, patient may be eligible to continue on study drug past 24 cycles (up to 4.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled subjects who received at least one dose of Ruxolitinib
Arm/Group Title Treatment (Ruxolitinib Phosphate)
Hide Arm/Group Description:

Patients 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.

Laboratory Biomarker Analysis: Correlative studies

Quality-of-Life Assessment: Ancillary studies

Questionnaire Administration: Ancillary studies

Ruxolitinib Phosphate: Given PO

Overall Number of Participants Analyzed 49
Median (Full Range)
Unit of Measure: months
8.5
(.2 to 50.5)
7.Secondary Outcome
Title Percentage of Participants With Early Drop Off (Prior to Completion of Cycle 3)
Hide Description Percent (and 95% confidence interval) of subjects who discontinue Ruxolitinib prior to completion of cycle 3
Time Frame up to the end of cycle 3 (12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled subjects who received at least one dose of Ruxolitinib
Arm/Group Title Treatment (Ruxolitinib Phosphate)
Hide Arm/Group Description:

Patients 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.

Laboratory Biomarker Analysis: Correlative studies

Quality-of-Life Assessment: Ancillary studies

Questionnaire Administration: Ancillary studies

Ruxolitinib Phosphate: Given PO

Overall Number of Participants Analyzed 49
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
16
(7.3 to 30)
8.Secondary Outcome
Title Percentage of Participants Who Reach Cycle 7
Hide Description Report percent (and 95% confidence interval) of subjects who start cycle 7(complete cycle 6)
Time Frame Start of cycle 7
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled subjects who received at least one dose of Ruxolitinib
Arm/Group Title Treatment (Ruxolitinib Phosphate)
Hide Arm/Group Description:

Patients 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.

Laboratory Biomarker Analysis: Correlative studies

Quality-of-Life Assessment: Ancillary studies

Questionnaire Administration: Ancillary studies

Ruxolitinib Phosphate: Given PO

Overall Number of Participants Analyzed 49
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
65
(50 to 78)
9.Secondary Outcome
Title Percentage of Participants With Early Drop Off (After Completion of Cycle 3 and Prior to Completion of Cycle 6)
Hide Description Percent (and 95% confidence interval) of subjects who discontinue after completion of 3 cycles but prior to completion of 6 cycles
Time Frame Between cycle 3 and cycle 6
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled subjects who received at least one dose of Ruxolitinib
Arm/Group Title Treatment (Ruxolitinib Phosphate)
Hide Arm/Group Description:

Patients 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.

Laboratory Biomarker Analysis: Correlative studies

Quality-of-Life Assessment: Ancillary studies

Questionnaire Administration: Ancillary studies

Ruxolitinib Phosphate: Given PO

Overall Number of Participants Analyzed 49
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
18
(8.8 to 32)
10.Secondary Outcome
Title Maximum Clinical Responses
Hide Description

Percent (and 95% confidence interval) of subjects' maximum or "best" protocol-defined response [CR > PR > SD > PD]. Protocol-defined Response combines changes in white blood cell count, absolute neutrophil count, marrow findings and spleen size to define response (attached protocol, Section 10.6, Clinical Response, Table 6 and Table).

Duration of maximum response was not available from the final data set. PR requires > 50% reduction in white blood cell and absolute neutrophil counts, > 50% reduction in granulocytic hyperplasia (CNL) or granulocytic dyspoiesis (aCML), and > 25% reduction in spleen size.

Time Frame Up to 6 weeks after last dose of ruxolitinib phosphate
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled subjects who received at least one dose of ruxolitinib. Subject who withdraw prior to disease response evaluation are considered non-responders (PD). One subject who was inevaluable for response was included in the denominator.
Arm/Group Title Treatment (Ruxolitinib Phosphate)
Hide Arm/Group Description:

Patients 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.

Laboratory Biomarker Analysis: Correlative studies

Quality-of-Life Assessment: Ancillary studies

Questionnaire Administration: Ancillary studies

Ruxolitinib Phosphate: Given PO

Overall Number of Participants Analyzed 49
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Complete Response (CR)
8
(2.3 to 20)
Partial Response (PR)
24
(13 to 39)
Stable Disease (SD)
29
(17 to 43)
Progressive Disease (PD)
37
(23 to 52)
11.Secondary Outcome
Title Change in Spleen Size, Evaluated by Ultrasound
Hide Description Change in spleen size (median, range) evaluated by ultrasound at the start of cycle 7 (day 1, cycle 7) and the start of study (day 1, cycle 1). Spleen volume is 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. Spleen size is only one component of protocol-defined response and cannot be used to independently assess response. (see section 10.6, Clinical Response, Table 6 of attached study protocol) Change in spleen size is the difference between measurements: value at Day 1 Cycle 7 minus the value at Day 1 Cycle 1.
Time Frame Measured on Day1 Cycle 1 and Day 1 Cycle 7
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled subjects receiving at least one dose of Ruxolitinib, completed 6 cycles of study drug and a had 3-dimensional spleen measurements at baseline and the start of cycle 7.
Arm/Group Title Treatment (Ruxolitinib Phosphate)
Hide Arm/Group Description:

Patients 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.

Laboratory Biomarker Analysis: Correlative studies

Quality-of-Life Assessment: Ancillary studies

Questionnaire Administration: Ancillary studies

Ruxolitinib Phosphate: Given PO

Overall Number of Participants Analyzed 32
Median (Full Range)
Unit of Measure: cm^3
-219.7
(-1553.8 to 1061.4)
12.Secondary Outcome
Title Change in Symptom Score as Measured by a Modified Myeloproliferative Neoplasm Symptom Assessment Form [MPN-SAF]
Hide Description Myeloproliferative Neoplasm Symptom Assessment Form Total symptom score (MPN-SAF TSS) ranges from 0 (no symptoms) to 10 (worst imaginable symptoms). The score is a sum of 10 independent measurements, generating a final score ranging from 0 - 100 and collected at baseline and on day 1, cycle 7. Change in total symptom score (TSS Median, range) is reported for those achieving day 1, cycle 7 AND responding to all 10 survey questions at baseline and Day 1, Cycle 7. Change in TSS is calculated as score on Day 1 Cycle 7 minus score at baseline.
Time Frame Measured at baseline and Day 1 Cycle 7
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled subjects who received at least one dose of Ruxolitinib, completed 6 cycles of study drug and responded to all 10 survey questions at baseline and start of cycle 7.
Arm/Group Title Treatment (Ruxolitinib Phosphate)
Hide Arm/Group Description:

Patients 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.

Laboratory Biomarker Analysis: Correlative studies

Quality-of-Life Assessment: Ancillary studies

Questionnaire Administration: Ancillary studies

Ruxolitinib Phosphate: Given PO

Overall Number of Participants Analyzed 28
Median (Full Range)
Unit of Measure: score on a scale
-3.0
(-37.0 to 8.0)
13.Secondary Outcome
Title Overall Survival in All Enrolled Patients
Hide Description Kaplan-Meier methods will be used to estimate overall survival for all enrolled patients receiving at least one dose of Ruxolitinib.
Time Frame At stem-cell transplantation or up to 5 years after enrollment in the study
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled subjects receiving at least one dose of Ruxolitinib except 9 subjects who were censored at the time of stem-cell transplant
Arm/Group Title Treatment (Ruxolitinib Phosphate)
Hide Arm/Group Description:

Patients 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.

Laboratory Biomarker Analysis: Correlative studies

Quality-of-Life Assessment: Ancillary studies

Questionnaire Administration: Ancillary studies

Ruxolitinib Phosphate: Given PO

Overall Number of Participants Analyzed 49
Median (95% Confidence Interval)
Unit of Measure: months
17.9 [1] 
(14 to NA)
[1]
Early censoring prevented estimation of upper confidence limit. We chose to censor these subjects as the increased risk associated with transplantation would otherwise contaminate the survival data.
14.Secondary Outcome
Title Percentage of Patients Who Achieve Clinical Response of Partial Response or Better by CSF3R Mutation Status
Hide Description Compute the percent (and 95% confidence interval) of patients with protocol-defined objective response (CR+PR) and IWG-defined objective response (CR+PR) at the start of cycle 7 among all enrolled patients (n = 49). Protocol-defined Response combines changes in white blood cell count, absolute neutrophil count, marrow findings and spleen size to define response (attached protocol, Section 10.6, Clinical Response, Table 6 and Table). IWG-defined Response evaluates bone marrow cellularity and myeloblast percent, absence of osteopmyelofibrosis, peripheral blood elements (white blood cell, Neutrophil, Monocyte and platelet counts, hemoglobin density, percent blasts and Neutrophil precursors), symptom resolution, dysplasia, and spleen size to determine response (attached reference). Patients who withdraw prior to the start of cycle 7 are considered non-responders.
Time Frame Start of cycle 7
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled patients receiving at least one dose ruxolitinib and are evaluated for response at the start of cycle 7. Patients who withdraw prior to the start of cycle 7 are considered non-responders. One wildtype CSF3R patient was deemed inevaluable for response and was excluded from response evaluation
Arm/Group Title Wildtype CSF3R Mutant CSF3R
Hide Arm/Group Description:
Subjects with wildtype CSF3R
Subjects with mutant CSF3R
Overall Number of Participants Analyzed 22 26
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Protocol-defined Response
9
(1.1 to 29)
54
(33 to 73)
IWG-defined Response
0
(0 to 0)
15
(4.4 to 35)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Wildtype CSF3R, Mutant CSF3R
Comments 2-sample test for equality of proportions with continuity correction (Pearson's chi-square test statistic) comparing Wildtype and Mutant CSF3R status for protocol-defined objective response
Type of Statistical Test Equivalence
Comments 2-sample test for equality of proportions with continuity correction (Pearson's chi-square test statistic)
Statistical Test of Hypothesis P-Value 0.003
Comments p-value for protocol-defined objective response.
Method Chi-squared, Corrected
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Wildtype CSF3R, Mutant CSF3R
Comments 2-sample test for equality of proportions with continuity correction (Pearson's chi-square test statistic) comparing Wildtype and Mutant CSF3R status for IWG-defined objective response
Type of Statistical Test Equivalence
Comments 2-sample test for equality of proportions with continuity correction (Pearson's chi-square)
Statistical Test of Hypothesis P-Value 0.1
Comments p-value for IWG-defined objective response = 0.1
Method Fisher Exact
Comments [Not Specified]
Time Frame Adverse Events (AE) were collected from first dose of ruxolitinib until 30 days after last dose. Any AEs occurring more than 30 days after the last dose of study drug and believed related to study drug were reported. Study drug was administered up to 96 weeks. Patients receiving ongoing clinical benefit were eligible to continue receiving study drug (up to 5 years).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment (Ruxolitinib Phosphate)
Hide Arm/Group Description

Patients 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.

Laboratory Biomarker Analysis: Correlative studies

Quality-of-Life Assessment: Ancillary studies

Questionnaire Administration: Ancillary studies

Ruxolitinib Phosphate: Given PO

All-Cause Mortality
Treatment (Ruxolitinib Phosphate)
Affected / at Risk (%)
Total   36/49 (73.47%)    
Hide Serious Adverse Events
Treatment (Ruxolitinib Phosphate)
Affected / at Risk (%) # Events
Total   30/49 (61.22%)    
Blood and lymphatic system disorders   
Anemia  1  4/49 (8.16%)  4
Blood and lymphatic system disorders - Other, Specify  1  1/49 (2.04%)  1
Febrile neutropenia  1  1/49 (2.04%)  1
Leukocytosis  1  4/49 (8.16%)  5
Cardiac disorders   
Cardiac arrest  1  1/49 (2.04%)  1
Cardiac disorders - Other, Specify  1  1/49 (2.04%)  1
Chest pain - cardiac  1  1/49 (2.04%)  1
Heart failure  1  4/49 (8.16%)  4
Sinus bradycardia  1  1/49 (2.04%)  1
Eye disorders   
Retinal detachment  1  1/49 (2.04%)  1
Uveitis  1  1/49 (2.04%)  1
Gastrointestinal disorders   
Abdominal pain  1  1/49 (2.04%)  1
Constipation  1  1/49 (2.04%)  1
Gastrointestinal disorders - Other, Specify  1  2/49 (4.08%)  2
Lower gastrointestinal hemorrhage  1  1/49 (2.04%)  1
General disorders   
Death NOS  1  3/49 (6.12%)  3
Fatigue  1  2/49 (4.08%)  2
Fever  1  1/49 (2.04%)  1
Infections and infestations   
Infections and infestations - Other, Specify  1  2/49 (4.08%)  2
Lung infection  1  6/49 (12.24%)  6
Sepsis  1  1/49 (2.04%)  4
Skin infection  1  2/49 (4.08%)  2
Upper respiratory infection  1  3/49 (6.12%)  6
Urinary tract infection  1  2/49 (4.08%)  4
Injury, poisoning and procedural complications   
Hip fracture  1  1/49 (2.04%)  1
Postoperative hemorrhage  1  1/49 (2.04%)  1
Investigations   
Platelet count decreased  1  2/49 (4.08%)  2
Metabolism and nutrition disorders   
Dehydration  1  1/49 (2.04%)  2
Hypoglycemia  1  1/49 (2.04%)  1
Musculoskeletal and connective tissue disorders   
Avascular necrosis  1  1/49 (2.04%)  1
Back pain  1  2/49 (4.08%)  2
Generalized muscle weakness  1  1/49 (2.04%)  1
Muscle weakness lower limb  1  1/49 (2.04%)  2
Neck pain  1  1/49 (2.04%)  1
Pain in extremity  1  1/49 (2.04%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Specify  1  1/49 (2.04%)  1
Nervous system disorders   
Cognitive disturbance  1  1/49 (2.04%)  1
Dizziness  1  1/49 (2.04%)  1
Syncope  1  1/49 (2.04%)  1
Transient ischemic attacks  1  1/49 (2.04%)  1
Psychiatric disorders   
Anxiety  1  1/49 (2.04%)  1
Delirium  1  1/49 (2.04%)  1
Renal and urinary disorders   
Acute kidney injury  1  3/49 (6.12%)  3
Hematuria  1  1/49 (2.04%)  1
Respiratory, thoracic and mediastinal disorders   
Bronchopulmonary hemorrhage  1  1/49 (2.04%)  1
Dyspnea  1  1/49 (2.04%)  1
Epistaxis  1  1/49 (2.04%)  1
Pneumonitis  1  5/49 (10.20%)  5
Respiratory failure  1  1/49 (2.04%)  1
Stridor  1  1/49 (2.04%)  1
Skin and subcutaneous tissue disorders   
Skin and subcutaneous tissue disorders - Other, Specify  1  1/49 (2.04%)  1
Vascular disorders   
Hematoma  1  3/49 (6.12%)  3
Vascular disorders - Other, Specify  1  1/49 (2.04%)  2
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2.5%
Treatment (Ruxolitinib Phosphate)
Affected / at Risk (%) # Events
Total   27/49 (55.10%)    
Blood and lymphatic system disorders   
Anemia  1  16/49 (32.65%)  28
Leukocytosis  1  4/49 (8.16%)  5
Gastrointestinal disorders   
Diarrhea  1  1/49 (2.04%)  2
General disorders   
Fatigue  1  2/49 (4.08%)  3
Investigations   
Lymphocyte count decreased  1  3/49 (6.12%)  5
Platelet count decreased  1  7/49 (14.29%)  11
Metabolism and nutrition disorders   
Hyponatremia  1  3/49 (6.12%)  3
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Kim-Hien Dao
Organization: OHSU
Phone: 503-494-5074
EMail: daok@ohsu.edu
Layout table for additonal information
Responsible Party: Kim-Hien Dao, OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT02092324    
Other Study ID Numbers: IRB00010262
NCI-2014-00633 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
IRB00010262 ( Other Identifier: OHSU Knight Cancer Institute )
First Submitted: March 18, 2014
First Posted: March 20, 2014
Results First Submitted: August 17, 2020
Results First Posted: November 16, 2020
Last Update Posted: November 16, 2020