INCB018424 in Patients With Advanced Hematologic Malignancies
Condition: Acute Myeloid Leukemia; Acute Lymphocytic Leukemia; Myelodysplastic Syndrome; Chronic Myelogenous Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasms; Preleukemia; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hematologic Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes
Intervention: INCB018424
Intervention description: Starting dose: 25 mg by mouth (po) twice daily for 7 days each week for 4 weeks.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 51.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Advanced Hematologic Malignancies; Cancer; Blood; Bone marrow; Lymph nodes; JAK kinase inhibitor INCB018424 phosphate; Acute Myeloid Leukemia; AML; Acute Lymphocytic leukemia; ALL; Myelodysplastic Syndrome; MDS; Chronic myelogenous leukemia - Blast Crisis; CML; INCB018424

Summary:

      The goal of this clinical research study is to learn if ruxolitinib can help to control
      advanced hematological malignancies. The safety of this drug will also be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Must be at least 18 years of age.

          2. Patients must have relapsed/refractory leukemias for which no standard therapies
             exist. Patients with poor-risk myelodysplasia (MDS) and chronic myelomonocytic
             leukemia (CMML) who failed prior therapy are also candidates for this protocol.
             Relapsed/refractory leukemias include acute non-lymphocytic leukemia (AML) by World
             Health Organization (WHO) classification (i.e. >/= 20% blasts), acute lymphocytic
             leukemia (ALL), or chronic myelogenous leukemia (CML) in blast crisis. Patients with
             CML who are resistant to at least two tyrosine kinase inhibitors and have no standard
             stem cell transplant option are also eligible.

          3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

          4. A female of childbearing potential must have a negative serum or urine pregnancy test
             at screening. Women of child-bearing potential must use acceptable contraceptive
             methods, and must have a negative serum or urine pregnancy test within 2 weeks prior
             to beginning treatment on this trial. Nursing patients are excluded. Sexually active
             men must also use acceptable contraceptive methods for the duration of time on study.

          5. Must be able and willing to give written informed consent.

          6. In the absence of rapidly progressing disease, the interval from prior treatment to
             time of study drug administration should be at least 2 weeks for cytotoxic agents, or
             at least one week for noncytotoxic agents. Persistent clinically significant
             toxicities from prior chemotherapy must not be greater than grade 2.

          7. Patients must have the following clinical laboratory values unless considered due to
             leukemic organ involvement: 1.) Serum creatinine less than or equal to 2.0 mg/dl. 2.)
             Total bilirubin less than or equal to 1.5x the upper limit of normal unless considered
             due to Gilbert's syndrome or hemolysis. 3.) Alanine aminotransferase (ALT), and
             aspartate aminotransferase (AST) less than or equal to 2.5x the upper limit of normal
             unless considered due to organ leukemic involvement (then 5x).

          8. Patients with active central nervous system (CNS) disease are included and will be
             treated concurrently with intrathecal therapy. INCB018424 will not be administered by
             intrathecal route.

        Exclusion Criteria:

          1. Uncontrolled intercurrent illness including, but not limited to uncontrolled
             infection, symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric
             illness/social situations that would limit compliance with study requirements.

          2. Active heart disease including myocardial infarction within the previous 3 months,
             symptomatic coronary artery disease, arrhythmias not controlled by medication, or
             uncontrolled congestive heart failure.

          3. Current treatment or treatment within 2 weeks or 5 half-lives (whichever is longer)
             prior to the first dose of study medication with another investigational medication or
             current enrollment in another investigational drug protocol (unless there is evidence
             of rapidly progressive disease in which case a shorter interval from last therapy may
             be acceptable).

          4. Females who are pregnant or are currently breastfeeding.

          5. Patients receiving therapy with intermediate or high dose steroids greater than the
             equivalent of 10 mg prednisone per day are not allowed.

          6. Evidence of active hepatitis or human immunodeficiency virus (HIV) infection
             determined by screening laboratory test results or results within prior 3 months.

          7. Any unresolved toxicity equal to or greater than Grade 2 from previous anticancer
             therapy, except for stable chronic toxicities not expected to resolve, such as
             peripheral neurotoxicity.

          8. Incomplete recovery from any prior surgical procedures or had surgery within 4 weeks
             prior to study entry, excluding the placement of vascular access.

          9. Uncontrolled intercurrent illness or any concurrent condition that, in the
             Investigator's opinion, would jeopardize the safety of the patient or compliance with
             the protocol.

         10. In patients who are receiving medications known to be inhibitors or inducers of CYP3A4
             every effort will be made to change these medications to acceptable alternatives. If
             this is not safely possible, patients will be excluded from participation in the
             study. If a patient is already on the study, must be started on a CYP3A4 inhibitor,
             and is demonstrating benefit from the study, they will be seen twice weekly in the
             first cycle and weekly in the subsequent cycles for toxicity evaluation and their dose
             will be modified in the event of a toxicity related to the study drug.