Phase l/II Study of Ruxolitinib for Acute Leukemia
Phase l/II Study of Ruxolitinib for Acute Leukemia
The goal of this clinical research study is to find the highest tolerable dose of ruxolitinib
 that can be given to patients with acute leukemia and to learn if the study drug can help
 control the disease. The safety of the drug will also be studied.
The Study Drug:

 Ruxolitinib is designed to block a gene mutation that may be important in cancer cell growth
 and survival. By blocking the gene mutation, this may cause the cancer cells to die.

 Study Groups:

 If you are found to be eligible to take part in this study, you will be assigned to a study
 group based on when you join this study. Up to 30 participants will be enrolled in the Phase
 I portion of the study, and up to 136 participants will be enrolled in Phase II.

 If you are enrolled in the Phase I portion, the dose of ruxolitinib you receive will depend
 on when you joined this study. The first group of participants will receive the lowest dose
 level of ruxolitinib. Each new group will receive a higher dose of ruxolitinib than the group
 before it, if no intolerable side effects were seen. This will continue until the highest
 tolerable dose of ruxolitinib is found.

 If you are enrolled in the Phase II portion, you will receive ruxolitinib at the highest dose
 that was tolerated in the Phase I portion or at a lower dose.

 Study Drug Administration:

 You will take ruxolitinib tablet(s) by mouth 2 times a day on Days 1-28 of each 28-day study
 cycle.

 You will be asked to keep a diary to record the doses taken. You will be asked to bring your
 diary and any unused drug to your next visit.

 Study Visits:

 On Days 1, 7, 14, and 21 of Cycle 1:

 -  You will have a physical exam.

 -  Blood (about 2 teaspoons) will be drawn for routine tests.

 -  You will be asked about any treatments you may have had, any other drugs you may be
 taking, and any side effects you may be having.

 -  On Day 14 only, you will have a bone marrow aspiration performed to check the status of
 the disease.

 On Day 1 of Cycle 2:

 -  You will have a physical exam.

 -  You will be asked about any treatments you may have had, any other drugs you may be
 taking, and any side effects you may be having.

 -  Blood (about 2 teaspoons) will be drawn for routine tests.

 -  You will have a bone marrow aspiration performed to check the status of the disease.

 During Cycles 2 and beyond, blood (about 2 teaspoons) will be drawn for routine tests at
 least every 1-2 weeks. This blood may be drawn at a clinic close to your home.

 On Day 1 of Cycles 3, 6, 9, and beyond:

 -  You will have a physical exam.

 -  You will be asked about any treatments you may have had, any other drugs you may be
 taking, and any side effects you may be having.

 -  Blood (about 2 teaspoons) will be drawn for routine tests.

 -  You will have a bone marrow aspiration performed to check the status of the disease. On
 Day 1 of Cycle 3, this will only be done if your doctor thinks it is needed.

 Length of Study:

 You may continue taking the study drug for as long as the doctor thinks it is in your best
 interest. You will no longer be able to take the study drug if the disease gets worse or
 intolerable side effects occur.

 Your participation on the study will be over once you have completed the end-of-study visit
 and the follow-up call.

 End-of-Study Visit:

 After your last dose of study drug, you will have an end-of-study visit. At this visit, the
 following tests and procedures will be performed:

 -  You will have a physical exam.

 -  You will be asked about any treatments you may have had, any other drugs you may be
 taking, and any side effects you may be having.

 -  Blood (about 2 teaspoons) will be drawn for routine tests.

 -  You will have a bone marrow aspiration performed to check the status of the disease.

 Follow-Up:

 About one month after your end-of-study visit, the study staff will call and ask about any
 side effects you may be having. This call should last about 5 minutes.

 This is an investigational study. Ruxolitinib is FDA approved and commercially available for
 the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis,
 post-polycythemia vera (post-PV) myelofibrosis and post-essential thrombocythemia (post-ET)
 myelofibrosis. Its use to treat acute leukemia is investigational.

 Up to 166 patients will take part in this study. All will be enrolled at MD Anderson.
Inclusion Criteria:

 1. Must be >14 years of age

 2. Must be diagnosed with refractory or relapsed AML or ALL.

 3. Must have adequate organ function as demonstrated by the following: o Alanine
 Aminotransferase (ALT) (SGOT) and/or Aspartate Aminotransferase (AST) (SGPT) equal to
 or less than 1.5x upper limit of normal o Serum creatinine equal to or less than 2.5
 mg/dL

 4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2

 5. At least 2 weeks from prior leukemia-directed treatment to starting treatment drug
 (except for hydroxyurea, which is allowed if clinically indicated but should be
 stopped after 2 weeks of receiving study drug, and glucocorticoids, which are allowed
 but should be stopped upon starting treatment drug).

 6. Treatment-related toxicities from prior therapies must have resolved to Grade equal to
 or less than 1 (except for peripheral neuropathy, which should resolve to grade equal
 to or less than 2)

 7. No active malignancies with the exception of basal cell or squamous cell carcinoma of
 the skin, or carcinoma "in situ" of the cervix or breast.

 8. Females of childbearing potential (FCBP)(A female of childbearing potential is a
 sexually mature woman who: 1) has not undergone a hysterectomy or bilateral
 oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive
 months (i.e., has had menses at any time in the preceding 24 consecutive months) must
 have negative pregnancy test. FCBP and males participating in the study must agree to
 use a reliable form of contraception or to practice complete abstinence from
 heterosexual intercourse while participating in the study and for at least 28 days
 after discontinuation from the study. If pregnancy or a positive pregnancy test does
 occur in a study subject, treatment with the study drug must be immediately
 discontinued.

 Exclusion Criteria:

 1. Known positive status for HIV, or known active hepatitis A, B, or C infection.

 2. Any serious medical condition or psychiatric illness that would prevent, (as judged by
 the treating physician) the subject from signing the informed consent form or any
 condition, including the presence of laboratory abnormalities, which places the
 subject at unacceptable risk if he/she were to participate in the study or confounds
 the ability to interpret data from the study.

 3. Pregnant or lactating females.

 4. Acute promyelocytic leukemia

 5. Concurrent use of strong inducers or strong inhibitors of cytochrome P450 3A4
 (CYP3A4). Strong inducers are rifampin and St. John's Worth. Strong inhibitors are
 HIV-antivirals, clarythromycin, itraconazole, ketoconazole, nefazodone, and
 telithromycin.

 6. Participating in any other research trial.