Prospective Evaluation of Ruxolitinib Efficacy for CNL/aCML Patients with Mutation of CSF3R
The goal of this research study is to learn about the effects, good and/or bad, ruxolitinib has on patients with CNL or aCML. The safety of this drug will also be studied.
Disease Group: Leukemia
Treatment Agent: Ruxolitinib
Treatment Location: Both at MDACC & and Other Sites
Sponsor: Oregon Health & Science University
Primary Objectives To determine the proportion of patients with chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) who have a hematologic response to ruxolitinib (PR, CR, CRp). Secondary Objectives 1. To determine the frequency of grade 3 or 4 hematologic and non-hematologic adverse events experienced by subjects during therapy with ruxolitinib. 2. To determine whether hematologic responses correlate with certain types of mutations in CSF3R and reduction in mutant CSF3R allele burden in the peripheral blood. 3. To determine the maximum clinical responses for each subject and the median duration of maximum clinical responses. 4. To determine the mean % reduction of spleen size, estimated by volumne using the conventional prolate ellipsoid method as measured by ultrasound compare to baseline. 5. To determine the mean % reduction of total symptom score as measured by a modified MPN-SAF compared to start of study (day 1, cycle 1). 6. To determine overall survival in subjects who complete a minimum of 1 dose of study drug. 7. To determine the proportion of subjects who discontinue after completion of > 3 cycles but < 6 cycles. 8. To determine the proportion of subjects who discontinue prior to completion of cycle 3.
IRB Review and Approval Date: 05/05/2015
Recruitment Status: Open
Projected Accrual: 50
1) 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.
2) Subjects must have platelet count greater than 25,000 per microliter at baseline and at the start of study (day 1, cycle 1) visit.
3) 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.
4) Subjects must be willing to accept/continue transfusions to treat low hemoglobin levels.
5) Subjects must be 18 years or older, male or female.
6) Subjects must have a life expectancy of > 6 months.
1) Subjects unable to review and sign informed consent form.
2) Females who are pregnant or breastfeeding, and males and females who cannot comply with requirements to avoid fathering a child or becoming pregnant.
3) Subjects with known diagnosis of 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.
4) Subjects with inadequate liver (ALT/SGPT above 4X ULN or direct bilirubin 4X ULN AND the lab abnormalities are felt to be due to underlying liver dysfunction).
5) Subjects with end stage renal function (CrCl<15 mL/min or GFR <15 mL/min) regardless of whether hemodialysis is required.
6) Subjects with clinically serious infections requiring ongoing antibiotic therapy.
7) 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.
8) Subjects requiring therapeutic doses of anticoagulation or anti-platelet therapies (aspirin above 81mg daily, plavix or similar agents) AND platelet counts are below 50,000 on two different laboratory evaluations, separated by minimum of two weeks.
9) Taking investigational or commercial agents or therapies with the intent to treat the subject's malignancy other than those therapies permitted.
10) 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.
11) Previous allergic reactions to JAK inhibitors or excipients.
12) Prior therapy with ruxolitinib or other JAK inhibitors.
13) Subjects who have had major surgery within 4 weeks prior to entering the study.
14) Subjects who are anticipated to receive a transplant within the first 6 months of treatment on trial.
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