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NCT02092324

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

Completed Phase 2 Results posted Last updated 16 November 2020
What this trial tests

Phase 2 trial testing Laboratory Biomarker Analysis in Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative in 51 participants. Completed in 24 January 2020.

Timeline
8 July 2014
Primary endpoint
22 November 2019
24 January 2020

Quick facts

Lead sponsorOHSU Knight Cancer Institute
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment51
Start date8 July 2014
Primary completion22 November 2019
Estimated completion24 January 2020
Sites7 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

OHSU Knight Cancer Institute

Who can join

18 and older, any sex, with Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative or Chronic Neutrophilic Leukemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of First 25 Enrolled Patients With a Hematologic Response to Ruxolitinib (Complete Response (CR), Partial Response (PR)) Primary · Start of cycle 7

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

Protocol-defined Response
GroupValue95% CI
First 25 Enrolled Subjects3215 – 54
IWG-defined Response
GroupValue95% CI
First 25 Enrolled Subjects40.1 – 20
Percentage of Participant With Any Hematologic Grade III or IV Adverse Events. Secondary · Up to 6 weeks after last dose of ruxolitinib phosphate

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

GroupValue95% CI
Treatment (Ruxolitinib Phosphate)46.932.5 – 61.7
Percentage of Participants With Any Non-hematologic Grade III or IV Adverse Events. Secondary · Up to 6 weeks after last dose of ruxolitinib phosphate

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

GroupValue95% CI
Treatment (Ruxolitinib Phosphate)69.454.6 – 81.7
Percentage of Participants Who Achieved Clinical Response of Partial Response or Better Secondary · Start of cycle 7

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,

Protocol-defined Response
GroupValue95% CI
Treatment (Ruxolitinib Phosphate)3320 – 48
IWG-defined Response
GroupValue95% CI
Treatment (Ruxolitinib Phosphate)82.3 – 20
Median Time on Study (Months) for Early Drop Offs Secondary · End of cycle 6

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

GroupValue95% CI
Treatment (Ruxolitinib Phosphate)2.4.2 – 5.7
Median Time on Study (Months) for All Enrolled Subjects Secondary · 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)

Median and range of months on Ruxolitinib for all enrolled subjects

GroupValue95% CI
Treatment (Ruxolitinib Phosphate)8.5.2 – 50.5
Percentage of Participants With Early Drop Off (Prior to Completion of Cycle 3) Secondary · up to the end of cycle 3 (12 weeks)

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

GroupValue95% CI
Treatment (Ruxolitinib Phosphate)167.3 – 30
Percentage of Participants Who Reach Cycle 7 Secondary · Start of cycle 7

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

GroupValue95% CI
Treatment (Ruxolitinib Phosphate)6550 – 78
Percentage of Participants With Early Drop Off (After Completion of Cycle 3 and Prior to Completion of Cycle 6) Secondary · Between cycle 3 and cycle 6

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

GroupValue95% CI
Treatment (Ruxolitinib Phosphate)188.8 – 32
Maximum Clinical Responses Secondary · Up to 6 weeks after last dose of ruxolitinib phosphate

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% reducti

Complete Response (CR)
GroupValue95% CI
Treatment (Ruxolitinib Phosphate)82.3 – 20
Partial Response (PR)
GroupValue95% CI
Treatment (Ruxolitinib Phosphate)2413 – 39
Stable Disease (SD)
GroupValue95% CI
Treatment (Ruxolitinib Phosphate)2917 – 43
Progressive Disease (PD)
GroupValue95% CI
Treatment (Ruxolitinib Phosphate)3723 – 52
Change in Spleen Size, Evaluated by Ultrasound Secondary · Measured on Day1 Cycle 1 and Day 1 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 diff

GroupValue95% CI
Treatment (Ruxolitinib Phosphate)-219.7-1553.8 – 1061.4
Change in Symptom Score as Measured by a Modified Myeloproliferative Neoplasm Symptom Assessment Form [MPN-SAF] Secondary · Measured at baseline and Day 1 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.

GroupValue95% CI
Treatment (Ruxolitinib Phosphate)-3.0-37.0 – 8.0

Adverse events — posted to ClinicalTrials.gov

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).. Reporting threshold: 2.5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (Ruxolitinib Phosphate)
Serious: 30/49 (61%)
Deaths: 36/49

Serious adverse events (53 terms)

ReactionSystemTreatment (Ruxolitinib Pho…
Lung infectionInfections and infestations
PneumonitisRespiratory, thoracic and mediastinal disorders
AnemiaBlood and lymphatic system disorders
Heart failureCardiac disorders
LeukocytosisBlood and lymphatic system disorders
Acute kidney injuryRenal and urinary disorders
Death NOSGeneral disorders
HematomaVascular disorders
Upper respiratory infectionInfections and infestations
Back painMusculoskeletal and connective tissue disorders
FatigueGeneral disorders
Gastrointestinal disorders - Other, SpecifyGastrointestinal disorders
Infections and infestations - Other, SpecifyInfections and infestations
Platelet count decreasedInvestigations
Skin infectionInfections and infestations
Urinary tract infectionInfections and infestations
Abdominal painGastrointestinal disorders
AnxietyPsychiatric disorders
Avascular necrosisMusculoskeletal and connective tissue disorders
Blood and lymphatic system disorders - Other, SpecifyBlood and lymphatic system disorders
Bronchopulmonary hemorrhageRespiratory, thoracic and mediastinal disorders
Cardiac arrestCardiac disorders
Cardiac disorders - Other, SpecifyCardiac disorders
Chest pain - cardiacCardiac disorders
Cognitive disturbanceNervous system disorders
Other adverse events (7 terms — click to expand)

ReactionSystemTreatment (Ruxolitinib Pho…
AnemiaBlood and lymphatic system disorders
Platelet count decreasedInvestigations
LeukocytosisBlood and lymphatic system disorders
HyponatremiaMetabolism and nutrition disorders
Lymphocyte count decreasedInvestigations
FatigueGeneral disorders
DiarrheaGastrointestinal disorders

Most-reported serious reactions: Lung infection, Pneumonitis, Anemia, Heart failure, Leukocytosis, Acute kidney injury, Death NOS, Hematoma.

Data from ClinicalTrials.gov NCT02092324 adverse events section.

Sponsor's own 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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. STAT3 pathway in cancers: Past, present, and future.
    Wang HQ, Man QW, Huo FY, Gao X, et al · · 2022 · cited 123× · PMID 35356799 · DOI 10.1002/mco2.124
  2. Efficacy of Ruxolitinib in Patients With Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia.
    Dao KT, Gotlib J, Deininger MMN, Oh ST, et al · · 2020 · cited 87× · PMID 31880950 · DOI 10.1200/jco.19.00895
  3. JAK2 inhibitors for myeloproliferative neoplasms: what is next?
    Bose P, Verstovsek S. · · 2017 · cited 78× · PMID 28500170 · DOI 10.1182/blood-2017-04-742288
  4. Genomics of chronic neutrophilic leukemia.
    Maxson JE, Tyner JW. · · 2017 · cited 69× · PMID 28028025 · DOI 10.1182/blood-2016-10-695981
  5. Significant clinical response to JAK1/2 inhibition in a patient with CSF3R-T618I-positive atypical chronic myeloid leukemia.
    Dao KH, Solti MB, Maxson JE, Winton EF, et al · · 2014 · cited 65× · PMID 25180155 · DOI 10.1016/j.lrr.2014.07.002
  6. A phase II trial of ruxolitinib in combination with azacytidine in myelodysplastic syndrome/myeloproliferative neoplasms.
    Assi R, Assi R, Kantarjian HM, Garcia-Manero G, et al · · 2018 · cited 55× · PMID 29134664 · DOI 10.1002/ajh.24972
  7. CSF3R mutations have a high degree of overlap with CEBPA mutations in pediatric AML.
    Maxson JE, Ries RE, Wang YC, Gerbing RB, et al · · 2016 · cited 48× · PMID 27143256 · DOI 10.1182/blood-2016-04-709899
  8. JAK kinase targeting in hematologic malignancies: a sinuous pathway from identification of genetic alterations towards clinical indications.
    Springuel L, Renauld JC, Knoops L. · · 2015 · cited 46× · PMID 26432382 · DOI 10.3324/haematol.2015.132142

Verify or expand the search:

Other trials of Laboratory Biomarker Analysis

Trials testing the same drug.

Other recruiting trials for Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative

Currently open trials in the same condition.

Other OHSU Knight Cancer Institute trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02092324.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing