Pacritinib for Patients With Lower-Risk Myelodysplastic Syndromes (MDS)
Condition: Leukemia
MeSH terms: Preleukemia; Myelodysplastic Syndromes
Intervention: Pacritinib; 5-azacitidine; Decitabine
Intervention description: Part 1: Pacritinib 200 mg taken by mouth twice daily.
Part 2: Pacritinib dose decreased to 200 mg in the morning and 100 mg in the evening for the first cycle of combined therapy. If no toxicity is observed in first cycle of combined therapy, Pacritinib dose may be increased to 200 mg twice a day on subsequent cycles of combined therapy.; Part 2 Starting Dose of 5-azacitidine: 75 mg/m2 by vein on Days 1 - 5 of Cycles 5 and beyond.; Part 2 Starting Dose of Decitabine: 20 mg/m2 by vein on on Days 1 - 7 of Cycles 5 and beyond.
Intervention MeSH terms: Azacitidine; Decitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Leukemia; Myelodysplastic syndromes; MDS; Lower-risk; Pacritinib; 5-azacitidine; Azacitidine; 5-azacytidine; Vidaza; 5-AZC; AZA-CR; Ladakamycin; NSC-102816; Azacytidine; Decitabine; Dacogen

Summary:

      The goal of this clinical research study is to learn if pacritinib, either alone or in
      combination with azacitidine or decitabine, can help to control MDS.

      The safety of this drug and drug combination will also be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Signed informed consent indicating that patients are aware of the investigational
             nature of this study, in keeping with the policies of MD Anderson Cancer Center
             (MDACC), must be obtained prior to any study specific procedures.

          2. Patients with a histologically confirmed diagnosis of MDS by World Health Organization
             (WHO) classification, and lower-risk MDS as defined by the IPSS classification (Low or
             Int-1 disease) or R-IPSS classification (Very Low or Low) are eligible. Patients with
             MDS/MPD overlap syndromes including CMML are also eligible if they have Low or Int-1
             disease per IPSS. Patients may have received MDS-directed therapy (i.e. lenalidomide),
             although patients with prior exposure to hypomethylating agents (e.g. 5-azacitidine or
             decitabine) are not eligible.

          3. The interval from prior treatment to time of study drug administration is at least 1
             week (except for hydroxyurea or steroid therapy) with recovery from all prior
             therapy-related toxicities

          4. Age >/= 18 years old.

          5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

          6. Adequate liver function, as evidence by serum bilirubin </= 2x the laboratory normal
             range (except for patients with Gilbert's Disease) or an aspartate aminotransferase
             (AST) or alanine aminotransferase (ALT) of </= 2.5x the upper limit of normal (ULN) or
             </= 5x ULN if hepatic disease involvement is present as determined by the
             investigator.

          7. Serum creatinine (Cr) </= 2x ULN or 24-hour creatinine clearance >/=50 ml/min

          8. Subjects of reproductive potential must agree to the use of acceptable contraceptive
             methods for the duration of the time on study and a further 6 months after completion
             of treatment. Women of childbearing potential must have a negative blood or urine
             pregnancy test within 72 hours of start of treatment.

        Exclusion Criteria:

          1. Subjects with any prior exposure to the hypomethylating agents (5-azacitidine or
             decitabine) are excluded.

          2. Subjects with any prior exposure to JAK2 inhibitor therapy (i.e. ruxolitinib or prior
             pacritinib therapy) are excluded.

          3. Any prior or coexisting medical condition that in the investigator's judgment will
             substantially increase the risk associated with the subject's participation in the
             study.

          4. Psychiatric disorders or altered mental status precluding understanding of the
             informed consent process and/or completion of the necessary study procedures.

          5. Active uncontrolled serious infection or sepsis at study enrollment. Patients
             receiving antibiotics for infections that are under control may be included in the
             study.

          6. Gastrointestinal disorders that may significantly interfere with absorption of study
             drug.

          7. Subjects have received potent CYP3A inhibitors within 7 days prior to the initiation
             of study treatment.

          8. History of myocardial infarction, severe/unstable angina, or symptomatic congestive
             heart failure (New York Heart Failure (NYHA) Class III or IV congestive heart failure)
             within 6 months prior to study enrollment or Left ventricular ejection fraction (LVEF)
             <50%

          9. Impaired cardiac function including ongoing cardiac dysrhythmias of Grade > 2,
             ejection fraction < 50%, atrial fibrillation of any grade, or QTc prolongation > 450
             ms, or other factors that increase the risk of QT prolongation (i.e. family history of
             long QT interval syndrome, hypokalemia defined as serum potassium < 3.0 mEq/L)

         10. Diagnosis of other malignancies within the last 3 years other than curatively treated
             non-melanoma skin cancer, carcinoma in situ of the cervix, organ-confined or treated
             non-metastatic prostate cancer, in situ breast carcinoma after complete surgical
             resection, or superficial transitional cell bladder carcinoma.

         11. Known active Hepatitis A, B or C.

         12. Known HIV seropositivity.

         13. Women who are pregnant or lactating.