Clinical Trials /

Ruxolitinib for Patients With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

NCT01895842

Description:

The goal of this clinical research study is to find the highest tolerable dose of ruxolitinib that can be given to patients with low or intermediate-1 risk MDS. The safety of this drug will also be studied, and whether it can help to control the disease.

Related Conditions:
  • Myelodysplastic Syndromes
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Ruxolitinib</span> for Patients With Low or Intermediate-1 Risk Myelodysplastic Syndrome (<span class="go-doc-concept go-doc-disease">MDS</span>)

Title

  • Brief Title: Ruxolitinib for Patients With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
  • Official Title: Phase I Study of Ruxolitinib for Patients With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
  • Clinical Trial IDs

    NCT ID: NCT01895842

    ORG ID: 2013-0012

    NCI ID: NCI-2013-02204

    Trial Conditions

    Leukemia

    Trial Interventions

    Drug Synonyms Arms
    Ruxolitinib Jakafi, INCB018424, INC424 Ruxolitinib

    Trial Purpose

    The goal of this clinical research study is to find the highest tolerable dose of
    ruxolitinib that can be given to patients with low or intermediate-1 risk MDS. The safety
    of this drug will also be studied, and whether it can help to control the disease.

    Detailed Description

    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 4 groups of 3-6 participants will be
    enrolled in Part 1 of the study, and up to 7 participants will be enrolled in Part 2.

    If you are enrolled in Part 1, the dose of ruxolitinib you receive will depend on when you
    joined this study. The first group of participants will receive the lowest dose of
    ruxolitinib. The second group of participants will receive the lowest dose of ruxolitinib
    for 1 cycle and if no intolerable side effects are seen, the dose will increase to the next
    higher dose for Cycles 2 and beyond. The third group of participants will receive the
    higher dose taken by the second group for 1 cycle and if no intolerable side effects are
    seen, the dose will be increased for Cycles 2 and beyond. The fourth group of participants
    will take the higher dose taken by the third group for 1 cycle and if no intolerable side
    effects are seen, the dose will increase to the next higher dose for Cycles 2 and beyond.

    If you are enrolled in Part 2, you will receive ruxolitinib at the highest dose that was
    tolerated in Part 1.

    Study Drug Administration:

    Each cycle is 28 days.

    You will take ruxolitinib by mouth 2 times a day (about 12 hours apart), with or without
    food.

    Study Visits:

    One (1) time a week during Cycles 1 and 2 and then on Day 1 of Cycles 3 and beyond, blood
    (about 2-3 teaspoons) will be drawn for routine tests. On Day 28 of each cycle and Day 1 of
    Cycles 3 and beyond, this blood may also be used for cytogenetic testing if your doctor
    thinks it is needed.

    On Day 28 of Cycles 1 and 2 and then every 3 cycles, you will have a bone marrow aspiration
    to check the status of the disease and for cytogenetic testing, if your doctor thinks it is
    needed.

    On Day 28 of Cycle 1 and Day 1 of Cycles 3 and beyond, you will have a physical exam.

    If the doctor thinks it is needed, urine will be collected on Day 1 of each cycle for
    routine tests.

    Length of Dosing:

    You may continue taking the study drug for up to 2 years. You will no longer be able to
    take the study drug if the disease gets worse, if intolerable side effects occur, or if you
    are unable to follow study directions.

    Your participation on the study will be over after the end-of-dosing visit.

    End-of-Dosing Visit:

    After you are finished taking the study drug:

    - You will have a physical exam.

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

    - Blood (about 2-3 teaspoons) will be drawn for routine tests. This blood may also be
    used for cytogenetic testing if your doctor thinks it is needed.

    Follow-up Visit:

    About 30 days after the End-of-Dosing visit, a member of the study team will contact you by
    phone. You will be asked how you are feeling and about any side effects you may be
    experiencing. This phone call should take 10-15 minutes.

    This is an investigational study. Ruxolitinib is FDA approved and commercially available
    for the treatment of myelofibrosis. Its use in this study is investigational. The study
    doctor can explain how ruxolitinib is designed to work.

    Up to 31 participants will be enrolled in this study. All will take part at MD Anderson.

    Trial Arms

    Name Type Description Interventions
    Ruxolitinib Experimental Part 1: Dose of ruxolitinib received will depend when patient joined study. The first group of patients receive the lowest dose of ruxolitinib. Starting dose level for Part 1, 5 mg by mouth twice a day for a 28 day cycle. The second group of patients receive the lowest dose of ruxolitinib for 1 cycle and if no intolerable side effects are seen, the dose will increase to the next higher dose for Cycles 2 and beyond. The third group of patients receive the higher dose taken by the second group for 1 cycle and if no intolerable side effects are seen, the dose will be increased for Cycles 2 and beyond. The fourth group of patients take the higher dose taken by the third group for 1 cycle and if no intolerable side effects are seen, the dose will increase to the next higher dose for Cycles 2 and beyond. If patients enrolled in Part 2, they will receive ruxolitinib at the highest dose that was tolerated in Part 1. Ruxolitinib

    Eligibility Criteria

    Inclusion Criteria:

    1. Patients with previously treated low or intermediate-1 risk MDS by the IPSS
    classification (this is defined in table 1)

    2. Patients must have one of the following: elevated b2-microglobulin levels (defined as
    2 times compared to normal), carry a JAK2 mutation, or presence of phosphorylated p65
    NF-kB component in at least 5% of bone marrow cells.

    3. Signed informed consent indicating that patients are aware of the investigational
    nature of this study in keeping with the policies of UTMDACC.

    4. Age >/= 18 years old

    5. Prior therapy with growth factor support, lenalidomide, 5-azacytidine, decitabine or
    other investigational agents are allowed. A four week wash out period will be
    required before receiving study medication.

    6. Patients must have the following non-hematologic values Aspartate aminotransferase
    (AST/SGOT) and alanine aminotransferase (ALT/SGPT) </= 2.5 x Upper Limit of Normal
    (ULN) or </= 5.0 x ULN if hepatic involvement is present; Serum bilirubin </= 2 x
    ULN; Serum creatinine </= 2 x ULN or 24-hour creatinine clearance >/= 60 ml/min

    7. Patients with Childbearing potential must agree to use appropriate forms of birth
    control

    Exclusion Criteria:

    1. Previously untreated low or intermediate-1 risk MDS patients because there are
    approved therapies for these patients.

    2. Uncontrolled undercurrent illness that in the opinion of the treating physician would
    contraindicate the use of the drug.

    3. Patients with active infections including uncontrolled HIV infection, active
    hepatitis B, C, or any other symptomatic systemic infection requiring active therapy
    will be excluded from study

    4. Patients receiving potent CYP3A4 (such as but not limited to boceprevir,
    clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole,
    lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir,
    saquinavir, telaprevir, telithromycin, voriconazole) inhibitors will be excluded from
    the study.

    5. Women who are pregnant or lactating.

    6. Patients with a white blood cell count of more than 30x10^3 K/uL will not be eligible
    for this study.

    7. Patients that have received prior allogeneic stem cell transplantation are excluded
    from this study.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Maximum Tolerated Dose (MTD) of Ruxolitinib

    Secondary Outcome Measures

    Trial Keywords

    Leukemia

    Myelodysplastic syndrome

    MDS

    Low or intermediate-1 risk

    Maximum tolerated dose

    MTD

    Ruxolitinib

    Jakafi

    INCB018424

    INC424