Pacritinib Combined With Decitabine or Cytarabine in Older Patients With AML
Condition: Acute Myeloid Leukemia (AML)
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Pacritinib; Decitabine; Cytarabine
Intervention description: Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nanomolar (nM)and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit Janus kinase 1 (JAK1).; Commercial drug: For each cycle Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily.; Commercial drug: For each cycle Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily.
Intervention MeSH terms: Cytarabine; Decitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 65 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to see if a medicine called pacritinib is both safe and
      effective as a study intervention for patients with AML in combination with either decitabine
      or cytarabine. Pacritinib is an experimental drug that is being studied to treat acute
      myeloid leukemia (AML). Decitabine and cytarabine are both FDA approved drugs that are used
      in treatment of AML. Pacritinib is being tested in clinical trials and has not been submitted
      to the U.S. Food and Drug Administration (FDA) for approval for any indications. Pacritinib
      is a drug that is designed to slow down the growth of leukemic cells.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patient has unequivocal pathologic diagnosis of AML (≥ 20% blasts in the bone marrow
             based on World Health Organization (WHO) criteria), excluding acute promyelocytic
             leukemia t(15;17)(q22;q12); Promyelocytic leukemia gene (PML)- retinoic acid receptor
             alpha (RARA)

          2. Age ≥ 65 years old

          3. No prior treatment for AML except:

               -  Emergency leukapheresis

               -  Emergency treatment for hyperleukocytosis with hydroxyurea

               -  Cranial radiotherapy (RT) for Central Nervous System (CNS) leukostasis (one dose
                  only)

               -  Growth factor/cytokine support

          4. AML patients with therapy-related myeloid neoplasms are eligible if they have not
             received radiation therapy or chemotherapy (not including hormonal therapy) for their
             primary malignancy or disorder for ≥ 6 months. Hydroxyurea may be used at the
             investigator's discretion up to the first 28 days on Cycle 1 to maintain WBC
             <30,000/µl.

          5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

          6. Subjects must have adequate hepatic and renal function

          7. Female subject of child-bearing potential and male subjects with female partners of
             reproductive potential must use acceptable contraceptive methods

          8. Able to understand and to provide written informed consent

          9. Able to comply with all study procedures during the study including all visits and
             tests

         10. Willing to adhere to the prohibitions and restrictions specified in this protocol

         11. Patient must sign an informed consent form (ICF)

        Exclusion Criteria:

          1. Prior treatment with decitabine

          2. Prior treatment with cytarabine

          3. Prior treatment with pacritinib

          4. Presence of serious illness, medical condition, or other medical history, involving
             the heart, kidney, liver, or other organ system, including abnormal laboratory
             parameters, which, in the opinion of the Investigator, would be likely to interfere
             with a subject's participation in the study or with the interpretation of the results.

          5. Active, uncontrolled, clinically significant infection(s)

          6. Have other active malignancies (excluding other myeloid hematologic malignancies) or
             other malignancies within 12 months before enrollment, except curatively treated
             non-melanoma skin cancer, cervical intraepithelial neoplasia, organ-confined or
             treated non-metastatic prostate cancer with negative prostate-specific antigen, in
             situ breast carcinoma after complete surgical resection, or superficial transitional
             cell bladder carcinoma

          7. Are receiving any other investigational therapy or protocol-prohibited therapy

          8. Any prior or co-existing medical condition that in the Investigator's judgment will
             substantially increase the risk associated with the subject's participation in the
             study

          9. Psychiatric disorders or altered mental status precluding understanding of the
             informed consent process and/or completion of the necessary study procedures

         10. Any gastrointestinal (GI) or metabolic condition that could interfere with absorption
             of oral medication

         11. Inflammatory or chronic functional bowel disorder, such as Crohn's disease,
             inflammatory bowel disease, chronic diarrhea

         12. Clinically symptomatic and uncontrolled cardiovascular disease

         13. History of any of the following within 6 months: myocardial infarction,
             severe/unstable angina, or symptomatic congestive heart failure

         14. New York Heart Association Class III or IV congestive heart failure

         15. Patients with National Cancer Institute (NCI) Common Terminology for Adverse Events
             (CTCAE) grade 2 cardiac arrhythmias may be considered for inclusion with the approval
             of the investigator if the arrhythmias are stable, asymptomatic and unlikely to affect
             patient safety. Patients will be excluded if they have ongoing cardiac dysrhythmias of
             CTCAE grade 3, corrected QT interval (QTc) prolongation >450 ms by Fridericia method,
             or other factors that increase the risk for QT prolongation (eg, heart failure,
             hypokalemia [defined as serum potassium < 3.0 milliequivalent (mEq/L) that is
             persistent and refractory to correction], or family history of long QT interval
             syndrome).