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

This study is currently recruiting participants.
See Contacts and Locations
Verified May 2017 by Kim-Hien Dao, OHSU Knight Cancer Institute
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Kim-Hien Dao, OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT02092324
First received: March 18, 2014
Last updated: May 15, 2017
Last verified: May 2017
  Purpose
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 Intervention Phase
Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative Chronic Neutrophilic Leukemia Other: Laboratory Biomarker Analysis Other: Quality-of-Life Assessment Drug: Ruxolitinib Phosphate Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Prospective Evaluation of Ruxolitinib Efficacy for CNL/aCML Patients With Mutation of CSF3R

Resource links provided by NLM:


Further study details as provided by Kim-Hien Dao, OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • 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:
  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • Indicator variable for drop-off [ Time Frame: At 8 weeks ]
  • Indicator variable for drop-off [ Time Frame: Between course 3 and course 6 ]
  • Indicator variable for drop-off since treatment [ Time Frame: Up to 96 weeks ]
  • Indicator variable for reaching course 7 [ Time Frame: Day 1 of course 7 ]
  • Indicator variable for the time of drop-off since treatment [ Time Frame: Up to 96 weeks ]
  • 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).

  • Maximum clinical responses [ Time Frame: Up to 6 weeks after last dose of ruxolitinib phosphate ]
  • 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.

  • 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.

  • 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.


Estimated Enrollment: 50
Study Start Date: May 2014
Estimated Primary Completion Date: April 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (ruxolitinib phosphate)
Patients receive ruxolitinib phosphate PO every other day, QD, or BID on days 1-28. Treatment repeats every 28 days for 24 courses (96 weeks) in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Drug: Ruxolitinib Phosphate
Given PO
Other Names:
  • INCB-18424 Phosphate
  • Jakafi

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. Treatment repeats every 28 days for 24 courses (96 weeks) in the absence of disease progression or unacceptable toxicity.

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

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02092324

Locations
United States, California
Stanford Cancer Institute Recruiting
Palo Alto, California, United States, 94304
Contact: Jason R. Gotlib    650-736-1253    gotlib@stanford.org   
Principal Investigator: Jason R. Gotlib         
United States, Georgia
Emory University/Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Elliott F. Winton    404-778-4755    ewinton@emory.edu   
Principal Investigator: Elliott F. Winton         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Stephen Oh    314-362-8846    stoh@dom.wustl.edu   
Principal Investigator: Stephen Oh         
United States, Oregon
OHSU Knight Cancer Institute Recruiting
Portland, Oregon, United States, 97239
Contact: Kim-Hien Dao    503-494-7894    daok@ohsu.edu   
Principal Investigator: Kim-Hien Dao         
United States, Texas
UT Southwestern/Simmons Cancer Center-Dallas Recruiting
Dallas, Texas, United States, 75390
Contact: Robert H. Collins    214-648-4155    robert.collins@utsouthwestern.edu   
Principal Investigator: Robert H. Collins         
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Jorge E. Cortes    713-794-5783    jcortes@mdanderson.org   
Principal Investigator: Jorge E. Cortes         
United States, Utah
Huntsman Cancer Institute/University of Utah Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Michael W. Deininger    801-213-5684    michael.deininger@hci.utah.edu   
Principal Investigator: Michael W. Deininger         
Sponsors and Collaborators
OHSU Knight Cancer Institute
National Cancer Institute (NCI)
Investigators
Principal Investigator: Kim-Hien Dao OHSU Knight Cancer Institute
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Kim-Hien Dao, Principal Investigator, OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT02092324     History of Changes
Other Study ID Numbers: IRB00010262
NCI-2014-00633 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
10262
IRB00010262 ( Other Identifier: OHSU Knight Cancer Institute )
P30CA069533 ( US NIH Grant/Contract Award Number )
Study First Received: March 18, 2014
Last Updated: May 15, 2017

Additional relevant MeSH terms:
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

ClinicalTrials.gov processed this record on June 23, 2017