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 July 2014 by OHSU Knight Cancer Institute
Sponsor:
Collaborator:
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT02092324
First received: March 18, 2014
Last updated: July 1, 2014
Last verified: July 2014
  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
Drug: ruxolitinib phosphate
Other: laboratory biomarker analysis
Other: quality-of-life assessment
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prospective Evaluation of Ruxolitinib Efficacy for CNL/aCML Patients With Mutation of CS3FR

Resource links provided by NLM:


Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • Proportion of patients with a hematologic response (PR, CR, CRp) [ Time Frame: Up to 2 weeks after last dose of ruxolitinib phosphate ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: Yes ]
    The frequency, duration, and severity of all adverse events will be assessed.

  • 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 ] [ Designated as safety issue: Yes ]
    The frequency, duration, and severity of all adverse events will be assessed.

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

  • Indicator variable for whether a patient has achieved clinical response of PR or better [ Time Frame: Day 1 of course 7 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Duration of maximum clinical responses [ Time Frame: Up to 6 weeks after last dose of ruxolitinib phosphate ] [ Designated as safety issue: No ]
    Summary statistics (mean, standard deviation, median, interquartile range) will be reported.

  • Change in spleen size, evaluated by ultrasound [ Time Frame: Baseline to day 1 of course 7 ] [ Designated as safety issue: No ]
    Summary statistics (mean, standard deviation, median, interquartile range) will be reported.

  • Change in symptom score as measured by a modified MPN-SAF [ Time Frame: Baseline to day 1 of course 7 ] [ Designated as safety issue: No ]
    Summary statistics (mean, standard deviation, median, interquartile range) will be reported.

  • Overall survival in patients who complete at least 6 courses [ Time Frame: Up to 5 years after enrollment in the study ] [ Designated as safety issue: No ]
    Kaplan-Meier methods will be used to illustrate and summarize overall survival in subjects who complete the study.


Estimated Enrollment: 33
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.
Drug: ruxolitinib phosphate
Given PO
Other Names:
  • INCB18424
  • Jakafi
  • oral JAK inhibitor INCB18424
  • oral Janus-associated kinase inhibitor INCB18424
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

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 the longest dimension in the cranio-caudal axis 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 6 cycles.

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
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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

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 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) regardless of whether hemodialysis is required
  • Subjects with clinically serious infections requiring ongoing antibiotic therapy
  • Subjects with unstable/recent severe cardiac or pulmonary dysfunction, recent gastric or esophageal variceal bleeding, recent hemorrhagic strokes or intracranial bleeds; unstable is defined as medical issue requiring urgent intervention (hospitalization) or daily or weekly monitoring by medical personnel; recent is defined as within the last 3 months
  • 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
  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
University of California Medical Center At Irvine-Irvine Campus Recruiting
Irvine, California, United States, 92697
Contact: Angela Fleischman    949-824-2559    agf@uci.edu   
Principal Investigator: Angela Fleischman         
Stanford University Medical Center Recruiting
Stanford, California, United States, 94305
Contact: Jason R. Gotlib    650-736-1253    gotlib@stanford.org   
Principal Investigator: Jason R. Gotlib         
United States, Colorado
University of Colorado Recruiting
Denver, Colorado, United States, 80217-3364
Contact: Daniel A. Pollyea    720-848-8084    daniel.pollyea@ucdenver.edu   
Principal Investigator: Daniel A. Pollyea         
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
University of Texas Southwestern Medical Center 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
Investigators
Principal Investigator: Kim-Hien Dao OHSU Knight Cancer Institute
  More Information

No publications provided

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT02092324     History of Changes
Other Study ID Numbers: 10262, NCI-2014-00633, 10262, P30CA069533
Study First Received: March 18, 2014
Last Updated: July 1, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia
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 September 30, 2014