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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02092324
Recruitment Status : Completed
First Posted : March 20, 2014
Last Update Posted : February 26, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Kim-Hien Dao, OHSU Knight Cancer Institute

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative Chronic Neutrophilic Leukemia Other: Laboratory Biomarker Analysis Other: Quality-of-Life Assessment Other: Questionnaire Administration Drug: Ruxolitinib Phosphate Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the proportion of patients with chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) who have a hematologic response to ruxolitinib (ruxolitinib phosphate) (partial response [PR], complete response [CR], complete response, partial [CRp]).

SECONDARY OBJECTIVES:

I. To determine the frequency of grade 3 or 4 hematologic and non-hematologic adverse events experienced by subjects during therapy with ruxolitinib.

II. To determine whether hematologic responses correlate with certain types of mutations in colony stimulating factor 3 receptor (CSF3R) and reduction in mutant CSF3R allele burden in the peripheral blood.

III. To determine the maximum clinical responses for each subject and the median duration of maximum clinical responses.

IV. To determine the mean % reduction of spleen size, estimated by volume using the conventional prolate ellipsoid method as measured by ultrasound compare to baseline.

V. To determine the mean % reduction of total symptom score as measured by a modified Myeloproliferative Neoplasm Symptom Assessment Form version 2.0 (MPN-SAF) compared to start of study (day 1, cycle 1).

VI. To determine overall survival in subjects who complete a minimum of 1 dose of study drug.

VII. To determine the proportion of subjects who discontinue after completion of > 3 cycles but < 6 cycles.

VIII. To determine the proportion of subjects who discontinue prior to completion of cycle 3.

OUTLINE:

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

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prospective Evaluation of Ruxolitinib Efficacy for CNL/aCML Patients With Mutation of CSF3R
Actual Study Start Date : May 5, 2014
Actual Primary Completion Date : November 22, 2019
Actual Study Completion Date : January 24, 2020


Arm Intervention/treatment
Experimental: 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.
Other: Laboratory Biomarker Analysis
Correlative studies

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Drug: Ruxolitinib Phosphate
Given PO
Other Names:
  • INCB-18424 Phosphate
  • Jakafi




Primary Outcome Measures :
  1. Proportion of patients with a hematologic response (partial response, complete response, complete response, partial) [ Time Frame: Up to 2 weeks after last dose of ruxolitinib phosphate ]
    A subject is defined as being responsive if he or she has achieved partial response, complete response, or complete response, partial. Proportions with 95% exact confidence intervals will be computed. Chi-square tests will be used to assess the association between hematologic response and mutant CSF3R type, and >= 50% reduction mutant CSF3R allele burden.


Secondary Outcome Measures :
  1. Incidence of any hematologic grade III or IV adverse events for thrombocytopenia, anemia, and neutropenia [ Time Frame: Up to 6 weeks after last dose of ruxolitinib phosphate ]
    The frequency, duration, and severity of all adverse events will be assessed.

  2. Incidence of any grade III or IV adverse events or any effects/toxicities directly attributed to study drug requiring permanent cessation of drug [ Time Frame: Up to 6 weeks after last dose of ruxolitinib phosphate ]
    The frequency, duration, and severity of all adverse events will be assessed.

  3. Proportion of patients with new onset of grade IV thrombocytopenia events, as measured by Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: Up to 6 weeks after last dose of ruxolitinib phosphate ]
    Tabulated with summary statistics. The hazard functions of time to onset will be estimated using life table method.

  4. Proportion of patients with new onset of grade III or higher hemorrhage, as measured by Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: Up to 6 weeks after last dose of ruxolitinib phosphate ]
    Tabulated with summary statistics. The hazard functions of time to onset will be estimated using life table method.

  5. Indicator variable for whether a patient has achieved clinical response of partial response or better [ Time Frame: Day 1 of course 7 ]
    Used to compute the proportion of such patients among all patients who carry a mutant CSF3R and have a more than 25% reduction in mutant CSF3R allele burden with ruxolitinib phosphate therapy compare to start of study (day 1, cycle 1).

  6. Indicator variable for drop-off since treatment [ Time Frame: Up to 96 weeks. If the study drug continues to be effective, the patient may be eligible to continue on study drug past 24 cycles. ]
  7. Indicator variable for the time of drop-off since treatment [ Time Frame: Up to 96 weeks. If the study drug continues to be effective, the patient may be eligible to continue on study drug past 24 cycles. ]
  8. Indicator variable for drop-off [ Time Frame: At 8 weeks ]
  9. Indicator variable for drop-off [ Time Frame: Between course 3 and course 6 ]
  10. Indicator variable for reaching course 7 [ Time Frame: Day 1 of course 7 ]
  11. Maximum clinical responses [ Time Frame: Up to 6 weeks after last dose of ruxolitinib phosphate ]
  12. Duration of maximum clinical responses [ Time Frame: Up to 6 weeks after last dose of ruxolitinib phosphate ]
    Summary statistics (mean, standard deviation, median, interquartile range) will be reported.

  13. Change in spleen size, evaluated by ultrasound [ Time Frame: Baseline to day 1 of course 7 ]
    Summary statistics (mean, standard deviation, median, interquartile range) will be reported. Spleen volume will be calculated by the conventional prolate ellipsoid method. Measure spleen width, thickness and maximum length in centimeters. Multiply width by thickness by max length by 0.524 to get the total spleen volume in cm^3.

  14. Change in symptom score as measured by a modified myeloproliferative neoplasm symptom assessment form [ Time Frame: Baseline to day 1 of course 7 ]
    Summary statistics (mean, standard deviation, median, interquartile range) will be reported.

  15. Overall survival in patients who complete at least 6 courses [ Time Frame: Up to 5 years after enrollment in the study ]
    Kaplan-Meier methods will be used to illustrate and summarize overall survival in subjects who complete the study.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must be newly diagnosed or previously diagnosed with CNL or aCML; all patients must have a bone marrow biopsy completed during the screening or baseline period if one has not been done within 90 days of day 1, cycle one
  • Subjects must have platelet count greater than 25,000 per microliter at baseline and at the start of study (day 1, cycle 1) visit
  • Subjects must be able to discontinue any drug treatment aimed at lowering disease burden in CNL or aCML; subjects should discontinue hydroxyurea to treat underlying CNL or aCML disease no later than day -7 (one week before starting ruxolitinib); for drugs that have more long-lasting effects on the marrow, such as thalidomide and its analogs, and interferon, subjects should discontinue these no later than day -28
  • Subjects must be willing to accept/continue transfusions to treat low hemoglobin levels
  • Subjects must have a life expectancy of > 6 months

Exclusion Criteria:

  • Subjects unable to review and sign informed consent form
  • Females who are pregnant or breastfeeding, and males and females who cannot comply with requirements to avoid fathering a child or becoming pregnant
  • Subjects with known diagnosis of human immunodeficiency virus (HIV) or chronic active Hepatitis B or C; viral testing is not required; subjects with a history of Hepatitis B and/or C are allowed on trial if the virus is undetected at the time of enrollment
  • Subjects with inadequate liver (alanine aminotransferase [ALT]/serum glutamate pyruvate transaminase [SGPT] above 4 X upper limit of normal [ULN] or direct bilirubin 4 X ULN AND the lab abnormalities are felt to be due to underlying liver dysfunction)
  • Subjects with end stage renal function (creatinine clearance [CrCl] < 15 mL/min or glomerular filtration rate [GFR] <15 mL/min) regardless of whether hemodialysis is required
  • Subjects with clinically serious infections requiring ongoing antibiotic therapy
  • Subjects with severe (immediately life threatening) and recent (occurring within the last 3 months) cardiac dysfunction, pulmonary dysfunction, esophageal variceal bleeding, hemorrhagic strokes, or intracranial hemorrhage are not eligible for study participation
  • Subjects requiring therapeutic doses of anticoagulation or anti-platelet therapies (aspirin above 81 mg daily, Plavix or similar agents) AND platelet counts are below 50,000 on two different laboratory evaluations, separated by minimum of two weeks
  • Taking investigational or commercial agents or therapies with the intent to treat the subject's malignancy other than those therapies permitted
  • Subjects with invasive malignancy over the previous 2 years except treated early stage carcinomas of the skin, completely resected intraepithelial carcinoma of the cervix, and completely resected papillary thyroid and follicular thyroid cancers
  • Previous allergic reactions to janus kinase (JAK) inhibitors or excipients
  • Prior therapy with ruxolitinib or other JAK inhibitors
  • Subjects who have had major surgery within 4 weeks prior to entering the study
  • Subjects who are anticipated to receive a transplant within the first 6 months of treatment on trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02092324


Locations
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United States, California
Stanford Cancer Institute Palo Alto
Palo Alto, California, United States, 94304
United States, Georgia
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Oregon
OHSU Knight Cancer Institute
Portland, Oregon, United States, 97239
United States, Texas
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, United States, 75390
M D Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Utah
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
OHSU Knight Cancer Institute
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Kim-Hien Dao OHSU Knight Cancer Institute
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Kim-Hien Dao, Principal Investigator, OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT02092324    
Other Study ID Numbers: IRB00010262
NCI-2014-00633 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
10262
IRB00010262 ( Other Identifier: OHSU Knight Cancer Institute )
P30CA069533 ( U.S. NIH Grant/Contract )
First Posted: March 20, 2014    Key Record Dates
Last Update Posted: February 26, 2020
Last Verified: February 2020
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, Neutrophilic, Chronic
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Myelodysplastic-Myeloproliferative Diseases