Trial Outcomes & Findings for Ruxolitinib Phosphate in Treating Patients With Chronic Neutrophilic Leukemia or Atypical Chronic Myeloid Leukemia (NCT NCT02092324)

NCT ID: NCT02092324

Last Updated: 2020-11-16

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

51 participants

Primary outcome timeframe

Start of cycle 7

Results posted on

2020-11-16

Participant Flow

The first patient was enrolled July 8, 2014 and recruitment ended in September 2019, across seven medical centers in the US.

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.

Participant milestones

Participant milestones
Measure	Treatment (Ruxolitinib Phosphate) 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.
Overall Study STARTED	51
Overall Study End of Cycle 6	25
Overall Study Wildtype CSF3R	23
Overall Study Mutant CSF3R	26
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	19

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Ruxolitinib Phosphate) 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.
Overall Study Adverse Event	1
Overall Study Lack of Efficacy	6
Overall Study Proceed to Transplant	3
Overall Study Physician Decision	7
Overall Study Misdiagnosis	2

Baseline Characteristics

Four subjects did not have baseline spleen size evaluated in three-dimensions by ultrasound

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Wildtype CSF3R n=23 Participants Subjects with wild type granulocyte Colony Stimulating Factor Receptor 3 (CSF3R)	Mutant CSF3R n=26 Participants Subjects with mutant CSF3R	Total n=49 Participants Total of all reporting groups
Age, Continuous	72.8 years n=23 Participants	73.0 years n=26 Participants	72.8 years n=49 Participants
Sex: Female, Male Female	8 Participants n=23 Participants	12 Participants n=26 Participants	20 Participants n=49 Participants
Sex: Female, Male Male	15 Participants n=23 Participants	14 Participants n=26 Participants	29 Participants n=49 Participants
Race/Ethnicity, Customized White	21 Participants n=23 Participants	26 Participants n=26 Participants	47 Participants n=49 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=23 Participants	0 Participants n=26 Participants	2 Participants n=49 Participants
Disease group CNL	5 Participants n=23 Participants	17 Participants n=26 Participants	22 Participants n=49 Participants
Disease group aCML	18 Participants n=23 Participants	9 Participants n=26 Participants	27 Participants n=49 Participants
Splenomegaly at baseline No Splenomegaly	6 Participants n=23 Participants	3 Participants n=26 Participants	9 Participants n=49 Participants
Splenomegaly at baseline Splenomegaly	17 Participants n=23 Participants	23 Participants n=26 Participants	40 Participants n=49 Participants
Spleen volume by ultrasound	582.8 cm^3 n=20 Participants • Four subjects did not have baseline spleen size evaluated in three-dimensions by ultrasound	586.9 cm^3 n=25 Participants • Four subjects did not have baseline spleen size evaluated in three-dimensions by ultrasound	586.9 cm^3 n=45 Participants • Four subjects did not have baseline spleen size evaluated in three-dimensions by ultrasound
Palpable spleen length at left midcostochondral line (LMC)	9.0 cm n=15 Participants • 17 subjects did not have measureable or palpable spleen at baseline	5.0 cm n=17 Participants • 17 subjects did not have measureable or palpable spleen at baseline	5.8 cm n=32 Participants • 17 subjects did not have measureable or palpable spleen at baseline
White blood cell count	48.1 10^9 cells/L n=23 Participants	51.6 10^9 cells/L n=26 Participants	50.7 10^9 cells/L n=49 Participants
Absolute Neutrophil Count (ANC)	35.4 10^9 cells/L n=23 Participants	46.0 10^9 cells/L n=26 Participants	41.9 10^9 cells/L n=49 Participants
Hemoglobin	11.0 g/dL n=23 Participants	10.4 g/dL n=26 Participants	10.8 g/dL n=49 Participants
Platelets	134 10^9 cells/L n=23 Participants	125 10^9 cells/L n=26 Participants	130 10^9 cells/L n=49 Participants
Prior therapy None	10 Participants n=23 Participants	8 Participants n=26 Participants	18 Participants n=49 Participants
Prior therapy Prior therapy	13 Participants n=23 Participants	18 Participants n=26 Participants	31 Participants n=49 Participants
Type of prior therapy Hydroxyurea	11 Participants n=23 Participants	15 Participants n=26 Participants	26 Participants n=49 Participants
Type of prior therapy Hydroxyurea + Azacitidine	1 Participants n=23 Participants	0 Participants n=26 Participants	1 Participants n=49 Participants
Type of prior therapy Hydroxyurea + Dasatinib	1 Participants n=23 Participants	0 Participants n=26 Participants	1 Participants n=49 Participants
Type of prior therapy Decitabine	0 Participants n=23 Participants	2 Participants n=26 Participants	2 Participants n=49 Participants
Type of prior therapy Other (interferon)	0 Participants n=23 Participants	1 Participants n=26 Participants	1 Participants n=49 Participants
Type of prior therapy No prior treatment	10 Participants n=23 Participants	8 Participants n=26 Participants	18 Participants n=49 Participants
IPSS total score	2.0 units on a scale n=23 Participants	2.5 units on a scale n=26 Participants	2.0 units on a scale n=49 Participants
MPN-SAF TSS	28.0 units on a scale n=21 Participants • Three subjects failed to respond to all 10 questions required to score TSS	20.0 units on a scale n=25 Participants • Three subjects failed to respond to all 10 questions required to score TSS	23.5 units on a scale n=46 Participants • Three subjects failed to respond to all 10 questions required to score TSS
Prestudy disease duration, months	0.9 months n=23 Participants	1.2 months n=26 Participants	0.9 months n=49 Participants

PRIMARY outcome

Timeframe: Start of cycle 7

Population: 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

Outcome measures

Outcome measures
Measure	First 25 Enrolled Subjects n=25 Participants First 25 enrolled subjects evaluated for protocol-defined objective response	Mutant CSF3R Subjects with mutant CSF3R
Percentage of First 25 Enrolled Patients With a Hematologic Response to Ruxolitinib (Complete Response (CR), Partial Response (PR)) Protocol-defined Response	32 percentage of participants Interval 15.0 to 54.0	—
Percentage of First 25 Enrolled Patients With a Hematologic Response to Ruxolitinib (Complete Response (CR), Partial Response (PR)) IWG-defined Response	4 percentage of participants Interval 0.1 to 20.0	—

SECONDARY outcome

Timeframe: Up to 6 weeks after last dose of ruxolitinib phosphate

Population: All subjects receiving at least one dose of ruxolitinib

The frequency (percentage) of subjects with any hematologic \[thrombocytopenia, anemia or neutropenia\] grade III or IV adverse events according to CTCAE v4.0

Outcome measures

Outcome measures
Measure	First 25 Enrolled Subjects n=49 Participants First 25 enrolled subjects evaluated for protocol-defined objective response	Mutant CSF3R Subjects with mutant CSF3R
Percentage of Participant With Any Hematologic Grade III or IV Adverse Events.	46.9 percentage of participants Interval 32.5 to 61.7	—

SECONDARY outcome

Timeframe: Up to 6 weeks after last dose of ruxolitinib phosphate

Population: All subjects receiving at least one dose of ruxolitinib

The frequency (percentage) of subjects with any non-hematologic grade III or IV adverse events according to CTCAE v4.0

Outcome measures

Outcome measures
Measure	First 25 Enrolled Subjects n=49 Participants First 25 enrolled subjects evaluated for protocol-defined objective response	Mutant CSF3R Subjects with mutant CSF3R
Percentage of Participants With Any Non-hematologic Grade III or IV Adverse Events.	69.4 percentage of participants Interval 54.6 to 81.7	—

SECONDARY outcome

Timeframe: Start of cycle 7

Population: 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.

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).

Outcome measures

Outcome measures
Measure	First 25 Enrolled Subjects n=49 Participants First 25 enrolled subjects evaluated for protocol-defined objective response	Mutant CSF3R Subjects with mutant CSF3R
Percentage of Participants Who Achieved Clinical Response of Partial Response or Better Protocol-defined Response	33 percentage of participants Interval 20.0 to 48.0	—
Percentage of Participants Who Achieved Clinical Response of Partial Response or Better IWG-defined Response	8 percentage of participants Interval 2.3 to 20.0	—

SECONDARY outcome

Timeframe: End of cycle 6

Population: Enrolled subjects who received at least one dose of study drug but did not complete 6 full cycles of Ruxolitinib

Median and range of months on study for subjects who did not complete 6 cycles of Ruxolitinib

Outcome measures

Outcome measures
Measure	First 25 Enrolled Subjects n=17 Participants First 25 enrolled subjects evaluated for protocol-defined objective response	Mutant CSF3R Subjects with mutant CSF3R
Median Time on Study (Months) for Early Drop Offs	2.4 months Interval 0.2 to 5.7	—

SECONDARY outcome

Timeframe: 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)

Population: Enrolled subjects who received at least one dose of Ruxolitinib

Median and range of months on Ruxolitinib for all enrolled subjects

Outcome measures

Outcome measures
Measure	First 25 Enrolled Subjects n=49 Participants First 25 enrolled subjects evaluated for protocol-defined objective response	Mutant CSF3R Subjects with mutant CSF3R
Median Time on Study (Months) for All Enrolled Subjects	8.5 months Interval 0.2 to 50.5	—

SECONDARY outcome

Timeframe: up to the end of cycle 3 (12 weeks)

Population: Enrolled subjects who received at least one dose of Ruxolitinib

Percent (and 95% confidence interval) of subjects who discontinue Ruxolitinib prior to completion of cycle 3

Outcome measures

Outcome measures
Measure	First 25 Enrolled Subjects n=49 Participants First 25 enrolled subjects evaluated for protocol-defined objective response	Mutant CSF3R Subjects with mutant CSF3R
Percentage of Participants With Early Drop Off (Prior to Completion of Cycle 3)	16 percentage of participants Interval 7.3 to 30.0	—

SECONDARY outcome

Timeframe: Start of cycle 7

Population: Enrolled subjects who received at least one dose of Ruxolitinib

Report percent (and 95% confidence interval) of subjects who start cycle 7(complete cycle 6)

Outcome measures

Outcome measures
Measure	First 25 Enrolled Subjects n=49 Participants First 25 enrolled subjects evaluated for protocol-defined objective response	Mutant CSF3R Subjects with mutant CSF3R
Percentage of Participants Who Reach Cycle 7	65 percentage of participants Interval 50.0 to 78.0	—

SECONDARY outcome

Timeframe: Between cycle 3 and cycle 6

Population: Enrolled subjects who received at least one dose of Ruxolitinib

Percent (and 95% confidence interval) of subjects who discontinue after completion of 3 cycles but prior to completion of 6 cycles

Outcome measures

Outcome measures
Measure	First 25 Enrolled Subjects n=49 Participants First 25 enrolled subjects evaluated for protocol-defined objective response	Mutant CSF3R Subjects with mutant CSF3R
Percentage of Participants With Early Drop Off (After Completion of Cycle 3 and Prior to Completion of Cycle 6)	18 percentage of participants Interval 8.8 to 32.0	—

SECONDARY outcome

Timeframe: Up to 6 weeks after last dose of ruxolitinib phosphate

Population: 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.

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.

Outcome measures

Outcome measures
Measure	First 25 Enrolled Subjects n=49 Participants First 25 enrolled subjects evaluated for protocol-defined objective response	Mutant CSF3R Subjects with mutant CSF3R
Maximum Clinical Responses Complete Response (CR)	8 percentage of participants Interval 2.3 to 20.0	—
Maximum Clinical Responses Partial Response (PR)	24 percentage of participants Interval 13.0 to 39.0	—
Maximum Clinical Responses Stable Disease (SD)	29 percentage of participants Interval 17.0 to 43.0	—
Maximum Clinical Responses Progressive Disease (PD)	37 percentage of participants Interval 23.0 to 52.0	—

SECONDARY outcome

Timeframe: Measured on Day1 Cycle 1 and Day 1 Cycle 7

Population: 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.

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.

Outcome measures

Outcome measures
Measure	First 25 Enrolled Subjects n=32 Participants First 25 enrolled subjects evaluated for protocol-defined objective response	Mutant CSF3R Subjects with mutant CSF3R
Change in Spleen Size, Evaluated by Ultrasound	-219.7 cm^3 Interval -1553.8 to 1061.4	—

SECONDARY outcome

Timeframe: Measured at baseline and Day 1 Cycle 7

Population: 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.

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.

Outcome measures

Outcome measures
Measure	First 25 Enrolled Subjects n=28 Participants First 25 enrolled subjects evaluated for protocol-defined objective response	Mutant CSF3R Subjects with mutant CSF3R
Change in Symptom Score as Measured by a Modified Myeloproliferative Neoplasm Symptom Assessment Form [MPN-SAF]	-3.0 score on a scale Interval -37.0 to 8.0	—

SECONDARY outcome

Timeframe: At stem-cell transplantation or up to 5 years after enrollment in the study

Population: Enrolled subjects receiving at least one dose of Ruxolitinib except 9 subjects who were censored at the time of stem-cell transplant

Kaplan-Meier methods will be used to estimate overall survival for all enrolled patients receiving at least one dose of Ruxolitinib.

Outcome measures

Outcome measures
Measure	First 25 Enrolled Subjects n=49 Participants First 25 enrolled subjects evaluated for protocol-defined objective response	Mutant CSF3R Subjects with mutant CSF3R
Overall Survival in All Enrolled Patients	17.9 months Interval 14.0 to 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.	—

SECONDARY outcome

Timeframe: Start of cycle 7

Population: 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

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.

Outcome measures

Outcome measures
Measure	First 25 Enrolled Subjects n=22 Participants First 25 enrolled subjects evaluated for protocol-defined objective response	Mutant CSF3R n=26 Participants Subjects with mutant CSF3R
Percentage of Patients Who Achieve Clinical Response of Partial Response or Better by CSF3R Mutation Status Protocol-defined Response	9 percentage of participants Interval 1.1 to 29.0	54 percentage of participants Interval 33.0 to 73.0
Percentage of Patients Who Achieve Clinical Response of Partial Response or Better by CSF3R Mutation Status IWG-defined Response	0 percentage of participants Interval 0.0 to 0.0	15 percentage of participants Interval 4.4 to 35.0

Adverse Events

Treatment (Ruxolitinib Phosphate)

Serious events: 30 serious events

Other events: 27 other events

Deaths: 36 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Ruxolitinib Phosphate) n=49 participants at risk 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
Gastrointestinal disorders Abdominal pain	2.0% 1/49 • Number of events 1 • 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).
Renal and urinary disorders Acute kidney injury	6.1% 3/49 • Number of events 3 • 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).
Blood and lymphatic system disorders Anemia	8.2% 4/49 • Number of events 4 • 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).
Psychiatric disorders Anxiety	2.0% 1/49 • Number of events 1 • 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).
Musculoskeletal and connective tissue disorders Avascular necrosis	2.0% 1/49 • Number of events 1 • 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).
Musculoskeletal and connective tissue disorders Back pain	4.1% 2/49 • Number of events 2 • 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).
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, Specify	2.0% 1/49 • Number of events 1 • 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).
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	2.0% 1/49 • Number of events 1 • 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).
Cardiac disorders Cardiac arrest	2.0% 1/49 • Number of events 1 • 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).
Cardiac disorders Cardiac disorders - Other, Specify	2.0% 1/49 • Number of events 1 • 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).
Cardiac disorders Chest pain - cardiac	2.0% 1/49 • Number of events 1 • 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).
Nervous system disorders Cognitive disturbance	2.0% 1/49 • Number of events 1 • 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).
Gastrointestinal disorders Constipation	2.0% 1/49 • Number of events 1 • 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).
General disorders Death NOS	6.1% 3/49 • Number of events 3 • 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).
Metabolism and nutrition disorders Dehydration	2.0% 1/49 • Number of events 2 • 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).
Psychiatric disorders Delirium	2.0% 1/49 • Number of events 1 • 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).
Nervous system disorders Dizziness	2.0% 1/49 • Number of events 1 • 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).
Respiratory, thoracic and mediastinal disorders Dyspnea	2.0% 1/49 • Number of events 1 • 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).
Respiratory, thoracic and mediastinal disorders Epistaxis	2.0% 1/49 • Number of events 1 • 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).
General disorders Fatigue	4.1% 2/49 • Number of events 2 • 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).
Blood and lymphatic system disorders Febrile neutropenia	2.0% 1/49 • Number of events 1 • 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).
General disorders Fever	2.0% 1/49 • Number of events 1 • 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).
Gastrointestinal disorders Gastrointestinal disorders - Other, Specify	4.1% 2/49 • Number of events 2 • 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).
Musculoskeletal and connective tissue disorders Generalized muscle weakness	2.0% 1/49 • Number of events 1 • 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).
Cardiac disorders Heart failure	8.2% 4/49 • Number of events 4 • 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).
Vascular disorders Hematoma	6.1% 3/49 • Number of events 3 • 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).
Renal and urinary disorders Hematuria	2.0% 1/49 • Number of events 1 • 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).
Injury, poisoning and procedural complications Hip fracture	2.0% 1/49 • Number of events 1 • 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).
Metabolism and nutrition disorders Hypoglycemia	2.0% 1/49 • Number of events 1 • 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).
Infections and infestations Infections and infestations - Other, Specify	4.1% 2/49 • Number of events 2 • 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).
Blood and lymphatic system disorders Leukocytosis	8.2% 4/49 • Number of events 5 • 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).
Gastrointestinal disorders Lower gastrointestinal hemorrhage	2.0% 1/49 • Number of events 1 • 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).
Infections and infestations Lung infection	12.2% 6/49 • Number of events 6 • 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).
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	2.0% 1/49 • Number of events 2 • 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).
Musculoskeletal and connective tissue disorders Neck pain	2.0% 1/49 • Number of events 1 • 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).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Specify	2.0% 1/49 • Number of events 1 • 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).
Musculoskeletal and connective tissue disorders Pain in extremity	2.0% 1/49 • Number of events 1 • 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).
Investigations Platelet count decreased	4.1% 2/49 • Number of events 2 • 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).
Respiratory, thoracic and mediastinal disorders Pneumonitis	10.2% 5/49 • Number of events 5 • 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).
Injury, poisoning and procedural complications Postoperative hemorrhage	2.0% 1/49 • Number of events 1 • 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).
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.0% 1/49 • Number of events 1 • 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).
Eye disorders Retinal detachment	2.0% 1/49 • Number of events 1 • 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).
Infections and infestations Sepsis	2.0% 1/49 • Number of events 4 • 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).
Cardiac disorders Sinus bradycardia	2.0% 1/49 • Number of events 1 • 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).
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, Specify	2.0% 1/49 • Number of events 1 • 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).
Infections and infestations Skin infection	4.1% 2/49 • Number of events 2 • 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).
Respiratory, thoracic and mediastinal disorders Stridor	2.0% 1/49 • Number of events 1 • 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).
Nervous system disorders Syncope	2.0% 1/49 • Number of events 1 • 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).
Nervous system disorders Transient ischemic attacks	2.0% 1/49 • Number of events 1 • 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).
Infections and infestations Upper respiratory infection	6.1% 3/49 • Number of events 6 • 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).
Infections and infestations Urinary tract infection	4.1% 2/49 • Number of events 4 • 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).
Eye disorders Uveitis	2.0% 1/49 • Number of events 1 • 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).
Vascular disorders Vascular disorders - Other, Specify	2.0% 1/49 • Number of events 2 • 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).

Other adverse events

Other adverse events
Measure	Treatment (Ruxolitinib Phosphate) n=49 participants at risk 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
Blood and lymphatic system disorders Anemia	32.7% 16/49 • Number of events 28 • 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).
Gastrointestinal disorders Diarrhea	2.0% 1/49 • Number of events 2 • 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).
General disorders Fatigue	4.1% 2/49 • Number of events 3 • 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).
Metabolism and nutrition disorders Hyponatremia	6.1% 3/49 • Number of events 3 • 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).
Blood and lymphatic system disorders Leukocytosis	8.2% 4/49 • Number of events 5 • 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).
Investigations Lymphocyte count decreased	6.1% 3/49 • Number of events 5 • 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).
Investigations Platelet count decreased	14.3% 7/49 • Number of events 11 • 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).

Additional Information

Dr. Kim-Hien Dao

OHSU

Phone: 503-494-5074

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place