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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2014-00633 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| IRB00010262 | Other Identifier | OHSU Knight Cancer Institute |
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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.
PRIMARY OBJECTIVES:
I. To determine the proportion of patients with chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) who have a hematologic response to ruxolitinib (ruxolitinib phosphate) (partial response [PR], complete response [CR], complete response, partial [CRp]).
SECONDARY OBJECTIVES:
I. To determine the frequency of grade 3 or 4 hematologic and non-hematologic adverse events experienced by subjects during therapy with ruxolitinib.
II. To determine whether hematologic responses correlate with certain types of mutations in colony stimulating factor 3 receptor (CSF3R) and reduction in mutant CSF3R allele burden in the peripheral blood.
III. To determine the maximum clinical responses for each subject and the median duration of maximum clinical responses.
IV. To determine the mean % reduction of spleen size, estimated by volume using the conventional prolate ellipsoid method as measured by ultrasound compare to baseline.
V. To determine the mean % reduction of total symptom score as measured by a modified Myeloproliferative Neoplasm Symptom Assessment Form version 2.0 (MPN-SAF) compared to start of study (day 1, cycle 1).
VI. To determine overall survival in subjects who complete a minimum of 1 dose of study drug.
VII. To determine the proportion of subjects who discontinue after completion of > 3 cycles but < 6 cycles.
VIII. To determine the proportion of subjects who discontinue prior to completion of cycle 3.
OUTLINE:
Patients receive ruxolitinib phosphate orally (PO) every other day, once daily (QD), or twice daily (BID) on days 1-28. Each patient will be followed for a maximum of 96 weeks (24 cycles, 1 cycle is 4 weeks long). If the study drug continues to be effective, the patient may be eligible to continue on study drug past 24 cycles.
After completion of study treatment, patients are followed up within 2 weeks and at 4-6 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (ruxolitinib phosphate) | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Laboratory Biomarker Analysis | Other | Correlative studies |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of First 25 Enrolled Patients With a Hematologic Response to Ruxolitinib (Complete Response (CR), Partial Response (PR)) | 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). | Start of cycle 7 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participant With Any Hematologic Grade III or IV Adverse Events. | The frequency (percentage) of subjects with any hematologic [thrombocytopenia, anemia or neutropenia] grade III or IV adverse events according to CTCAE v4.0 | Up to 6 weeks after last dose of ruxolitinib phosphate |
| Percentage of Participants With Any Non-hematologic Grade III or IV Adverse Events. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kim-Hien Dao | OHSU Knight Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford Cancer Institute Palo Alto | Palo Alto | California | 94304 | United States | ||
| Emory University Hospital/Winship Cancer Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25624319 | Background | Savona MR, Malcovati L, Komrokji R, Tiu RV, Mughal TI, Orazi A, Kiladjian JJ, Padron E, Solary E, Tibes R, Itzykson R, Cazzola M, Mesa R, Maciejewski J, Fenaux P, Garcia-Manero G, Gerds A, Sanz G, Niemeyer CM, Cervantes F, Germing U, Cross NC, List AF; MDS/MPN International Working Group. An international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults. Blood. 2015 Mar 19;125(12):1857-65. doi: 10.1182/blood-2014-10-607341. Epub 2015 Jan 26. | |
| 31880950 |
| Label | URL |
|---|---|
| An international consortium proposal of uniform response criteria for myelodysplastic/myeloprolierative neoplasms (MDS/MPN) in adults | View source |
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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.
The first patient was enrolled July 8, 2014 and recruitment ended in September 2019, across seven medical centers in the US.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 7, 2017 |
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| Quality-of-Life Assessment |
| Other |
Ancillary studies |
|
|
| Questionnaire Administration | Other | Ancillary studies |
|
| Ruxolitinib Phosphate | Drug | Given PO |
|
|
The frequency (percentage) of subjects with any non-hematologic grade III or IV adverse events according to CTCAE v4.0 |
| Up to 6 weeks after last dose of ruxolitinib phosphate |
| Percentage of Participants Who Achieved Clinical Response of Partial Response or Better | 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). | Start of cycle 7 |
| Median Time on Study (Months) for Early Drop Offs | Median and range of months on study for subjects who did not complete 6 cycles of Ruxolitinib | End of cycle 6 |
| Median Time on Study (Months) for All Enrolled Subjects | Median and range of months on Ruxolitinib for all enrolled subjects | 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) |
| Percentage of Participants With Early Drop Off (Prior to Completion of Cycle 3) | Percent (and 95% confidence interval) of subjects who discontinue Ruxolitinib prior to completion of cycle 3 | up to the end of cycle 3 (12 weeks) |
| Percentage of Participants Who Reach Cycle 7 | Report percent (and 95% confidence interval) of subjects who start cycle 7(complete cycle 6) | Start of cycle 7 |
| Percentage of Participants With Early Drop Off (After Completion of Cycle 3 and Prior to Completion of Cycle 6) | Percent (and 95% confidence interval) of subjects who discontinue after completion of 3 cycles but prior to completion of 6 cycles | Between cycle 3 and cycle 6 |
| Maximum Clinical Responses | 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. | Up to 6 weeks after last dose of ruxolitinib phosphate |
| Change in Spleen Size, Evaluated by Ultrasound | 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. | Measured on Day1 Cycle 1 and Day 1 Cycle 7 |
| Change in Symptom Score as Measured by a Modified Myeloproliferative Neoplasm Symptom Assessment Form [MPN-SAF] | 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. | Measured at baseline and Day 1 Cycle 7 |
| Overall Survival in All Enrolled Patients | Kaplan-Meier methods will be used to estimate overall survival for all enrolled patients receiving at least one dose of Ruxolitinib. | At stem-cell transplantation or up to 5 years after enrollment in the study |
| Percentage of Patients Who Achieve Clinical Response of Partial Response or Better by CSF3R Mutation Status | 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. | Start of cycle 7 |
| Atlanta |
| Georgia |
| 30322 |
| United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| OHSU Knight Cancer Institute | Portland | Oregon | 97239 | United States |
| UT Southwestern/Simmons Cancer Center-Dallas | Dallas | Texas | 75390 | United States |
| M D Anderson Cancer Center | Houston | Texas | 77030 | United States |
| Huntsman Cancer Institute/University of Utah | Salt Lake City | Utah | 84112 | United States |
| Result |
| Dao KT, Gotlib J, Deininger MMN, Oh ST, Cortes JE, Collins RH Jr, Winton EF, Parker DR, Lee H, Reister A, Schultz, Savage S, Stevens, Brockett C, Subbiah N, Press RD, Raess PW, Cascio M, Dunlap J, Chen Y, Degnin C, Maxson JE, Tognon CE, Macey T, Druker BJ, Tyner JW. Efficacy of Ruxolitinib in Patients With Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia. J Clin Oncol. 2020 Apr 1;38(10):1006-1018. doi: 10.1200/JCO.19.00895. Epub 2019 Dec 27. |
| 25180155 | Derived | Dao KH, Solti MB, Maxson JE, Winton EF, Press RD, Druker BJ, Tyner JW. Significant clinical response to JAK1/2 inhibition in a patient with CSF3R-T618I-positive atypical chronic myeloid leukemia. Leuk Res Rep. 2014 Aug 1;3(2):67-9. doi: 10.1016/j.lrr.2014.07.002. eCollection 2014. |
| End of Cycle 6 | We expanded accrual to enroll additional evaluable subjects for analysis of the secondary endpoints. |
|
| Wildtype CSF3R | Participants were stratified by CSF3R mutation status |
|
| Mutant CSF3R | Participants were stratified by CSF3R mutation status |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Wildtype CSF3R | Subjects with wild type granulocyte Colony Stimulating Factor Receptor 3 (CSF3R) |
| BG001 | Mutant CSF3R | Subjects with mutant CSF3R |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Disease group | Count of Participants | Participants |
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| Splenomegaly at baseline | Count of Participants | Participants |
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| Spleen volume by ultrasound | Four subjects did not have baseline spleen size evaluated in three-dimensions by ultrasound | Median | Full Range | cm^3 |
| ||||||||||||||
| Palpable spleen length at left midcostochondral line (LMC) | 17 subjects did not have measureable or palpable spleen at baseline | Median | Full Range | cm |
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| White blood cell count | Median | Full Range | 10^9 cells/L |
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| Absolute Neutrophil Count (ANC) | Median | Full Range | 10^9 cells/L |
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| Hemoglobin | Median | Full Range | g/dL |
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| Platelets | Median | Full Range | 10^9 cells/L |
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| Prior therapy | Count of Participants | Participants |
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| Type of prior therapy | Count of Participants | Participants |
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| IPSS total score | 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". | Median | Full Range | units on a scale |
| ||||||||||||||
| MPN-SAF TSS | 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. | Three subjects failed to respond to all 10 questions required to score TSS | Median | Full Range | units on a scale |
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| Prestudy disease duration, months | Median | Full Range | months |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of First 25 Enrolled Patients With a Hematologic Response to Ruxolitinib (Complete Response (CR), Partial Response (PR)) | 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). | 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 | Posted | Number | 95% Confidence Interval | percentage of participants | Start of cycle 7 |
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| Secondary | Percentage of Participant With Any Hematologic Grade III or IV Adverse Events. | The frequency (percentage) of subjects with any hematologic [thrombocytopenia, anemia or neutropenia] grade III or IV adverse events according to CTCAE v4.0 | All subjects receiving at least one dose of ruxolitinib | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 6 weeks after last dose of ruxolitinib phosphate |
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| Secondary | Percentage of Participants With Any Non-hematologic Grade III or IV Adverse Events. | The frequency (percentage) of subjects with any non-hematologic grade III or IV adverse events according to CTCAE v4.0 | All subjects receiving at least one dose of ruxolitinib | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 6 weeks after last dose of ruxolitinib phosphate |
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| Secondary | Percentage of Participants Who Achieved Clinical Response of Partial Response or Better | 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). | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | Start of cycle 7 |
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| Secondary | Median Time on Study (Months) for Early Drop Offs | Median and range of months on study for subjects who did not complete 6 cycles of Ruxolitinib | Enrolled subjects who received at least one dose of study drug but did not complete 6 full cycles of Ruxolitinib | Posted | Median | Full Range | months | End of cycle 6 |
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| Secondary | Median Time on Study (Months) for All Enrolled Subjects | Median and range of months on Ruxolitinib for all enrolled subjects | Enrolled subjects who received at least one dose of Ruxolitinib | Posted | Median | Full Range | months | 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) |
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| Secondary | Percentage of Participants With Early Drop Off (Prior to Completion of Cycle 3) | Percent (and 95% confidence interval) of subjects who discontinue Ruxolitinib prior to completion of cycle 3 | Enrolled subjects who received at least one dose of Ruxolitinib | Posted | Number | 95% Confidence Interval | percentage of participants | up to the end of cycle 3 (12 weeks) |
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| Secondary | Percentage of Participants Who Reach Cycle 7 | Report percent (and 95% confidence interval) of subjects who start cycle 7(complete cycle 6) | Enrolled subjects who received at least one dose of Ruxolitinib | Posted | Number | 95% Confidence Interval | percentage of participants | Start of cycle 7 |
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| Secondary | Percentage of Participants With Early Drop Off (After Completion of Cycle 3 and Prior to Completion of Cycle 6) | Percent (and 95% confidence interval) of subjects who discontinue after completion of 3 cycles but prior to completion of 6 cycles | Enrolled subjects who received at least one dose of Ruxolitinib | Posted | Number | 95% Confidence Interval | percentage of participants | Between cycle 3 and cycle 6 |
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| Secondary | Maximum Clinical Responses | 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. | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 6 weeks after last dose of ruxolitinib phosphate |
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| Secondary | Change in Spleen Size, Evaluated by Ultrasound | 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. | 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. | Posted | Median | Full Range | cm^3 | Measured on Day1 Cycle 1 and Day 1 Cycle 7 |
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| Secondary | Change in Symptom Score as Measured by a Modified Myeloproliferative Neoplasm Symptom Assessment Form [MPN-SAF] | 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. | 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. | Posted | Median | Full Range | score on a scale | Measured at baseline and Day 1 Cycle 7 |
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| Secondary | Overall Survival in All Enrolled Patients | Kaplan-Meier methods will be used to estimate overall survival for all enrolled patients receiving at least one dose of Ruxolitinib. | Enrolled subjects receiving at least one dose of Ruxolitinib except 9 subjects who were censored at the time of stem-cell transplant | Posted | Median | 95% Confidence Interval | months | At stem-cell transplantation or up to 5 years after enrollment in the study |
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| Secondary | Percentage of Patients Who Achieve Clinical Response of Partial Response or Better by CSF3R Mutation Status | 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. | 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 | Posted | Number | 95% Confidence Interval | percentage of participants | Start of cycle 7 |
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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).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment (Ruxolitinib Phosphate) | 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 | 36 | 49 | 30 | 49 | 27 | 49 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Avascular necrosis | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Blood and lymphatic system disorders - Other, Specify | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Bronchopulmonary hemorrhage | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Cardiac disorders - Other, Specify | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Chest pain - cardiac | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Cognitive disturbance | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Death NOS | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Fever | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Gastrointestinal disorders - Other, Specify | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Heart failure | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hematoma | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hematuria | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hip fracture | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
| |
| Hypoglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Infections and infestations - Other, Specify | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Lower gastrointestinal hemorrhage | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Lung infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Muscle weakness lower limb | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Specify | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | CTCAE (4.0) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Postoperative hemorrhage | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Retinal detachment | Eye disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Skin and subcutaneous tissue disorders - Other, Specify | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Skin infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Stridor | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Transient ischemic attacks | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Upper respiratory infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Uveitis | Eye disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Vascular disorders - Other, Specify | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hyponatremia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Kim-Hien Dao | OHSU | 503-494-5074 | daok@ohsu.edu |
| Aug 13, 2020 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D054438 | Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative |
| D015467 | Leukemia, Neutrophilic, Chronic |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D054437 | Myelodysplastic-Myeloproliferative Diseases |
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009196 | Myeloproliferative Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| C540383 | ruxolitinib |
Not provided
Not provided
Not provided
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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). |
| binomial |
| 0.90 |
p-value is for IWG-defined objective response |
| Superiority |
1-proportion test for greater than 10% difference |
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| Participants |
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| Participants |
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Subjects with mutant CSF3R
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