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The starting dose of INCB018424 will be 25 mg by mouth twice daily.

Starting dose: 25 mg by mouth (po) twice daily for 7 days each week for 4 weeks.

INCB018424

Farhad Ravandi-Kashani, M.D.

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.

The Study Drug:

Ruxolitinib is designed to block the protein product of a mutated (changed) gene that may be important in cancer cell growth and survival.

Study Drug Administration:

If you are found to be eligible to take part in this study, every day of each 28-day cycle you will take ruxolitinib by mouth 2 times a day (in the morning and evening).

On Day 1 of each cycle, the morning dose of study drug should not be taken until you visit the clinic unless the doctor says differently.

If the doctor thinks it is necessary, your dose of study drug may be raised or lowered.

Study Visits:

On Day 1 of Cycle 1, the following tests and procedures will be performed:

* You will be asked to list any drugs you may be taking and if you have experienced any side effects.
* You will have a physical exam, including measurement of your vital signs.

On Days 8, 15, and 22 of Cycle 1 (+/- 2 days), the following tests and procedures will be performed (these can be done at your local physician's office):

* Your medical history will be reviewed, including any drugs you may be taking.
* You will be asked if you have experienced any side effects.
* You will have a physical exam, including measurement of your vital signs.
* Blood (about 2 tablespoons) will be drawn for routine tests.

On Day 1 of Cycles 2-4 (+/- 2 days) and then once every 3 months, the following tests and procedures will be performed:

* Your medical history will be reviewed, including any drugs you may be taking.
* You will be asked if you have experienced any side effects.
* You will have a physical exam, including measurement of your vital signs.
* You will have a performance status evaluation.
* Blood (about 2 tablespoons) will be drawn for routine tests.
* If the doctor thinks it is necessary, blood (about 1 tablespoon) will be drawn to check the status of the disease.
* If the doctor thinks it is necessary, you will have a bone marrow biopsy/aspirate to check the status of the disease.
* During these visits, you will also be receiving your new supply of medication.

On Days 8, 15, and 22 of Cycles 2 and 3, blood (about 2 tablespoons) will be drawn for routine tests at your local doctor's office.

On Day 1 of Cycles 4, 7, and every 6th cycle after that (Cycles 13, 19, 25, and so on), you will have a bone marrow aspiration or biopsy to check the status of the disease. On Day 1 of Cycle 4, the bone marrow aspiration/biopsy will also look at the genes and chromosomes of the leukemia cells. If there is not enough information from the biopsy/aspirate, leftover blood will be used to look at this gene and chromosome information.

Every 2 weeks of Cycles 4-7, blood (about 2 tablespoons) will be drawn for routine tests.

You will be called once a month while you are on study. During this phone call you will be asked how you are doing, if you have experienced any side effects, and if you are taking the study drug at the correct dose and time. This phone call will take a few minutes. You will be sent a card in the mail to remind you about any study visits you need to complete.

Women who are able to become pregnant will have a urine pregnancy test if there is a suspicion of pregnancy. If the test is positive, they will then have a blood (about 1 teaspoon) pregnancy test.

Length of Study:

You may stay on study for as long as you are benefitting. You will be taken off study if you experience intolerable side effects or the disease gets worse.

End-of-Study Visit:

After you go off study you will have an end-of-study visit. At this visit, the following tests and procedures will be performed:

* Your medical history will be reviewed, including any drugs you may be taking.
* You will be asked if you have experienced any side effects.
* You will have a physical exam, including measurement of your vital signs.
* You will have a performance status evaluation.
* Blood (about 2 tablespoons) will be drawn for routine tests.
* If the doctor thinks it is necessary, blood (about 1 tablespoon) will be drawn to check the status of the disease.
* If the doctor thinks it is necessary, you will have a bone marrow biopsy/aspirate to check the status of the disease.
* Women who are able to become pregnant will have a urine pregnancy test. If the test is positive, they will then have a blood (about 1 teaspoon) pregnancy test.

This is an investigational study. Ruxolitinib is FDA approved and commercially available to treat myelofibrosis. Giving ruxolitinib to patients with advanced hematological malignancies is investigational.

Up to 120 patients will take part in this study. All will be enrolled at M. D. Anderson.

INCB018424 in Patients With Advanced Hematologic Malignancies

Phase II Study of INCB018424 in Patients With Advanced Hematologic Malignancies

The PD parameters will be calculated to explore preliminary evidence of PD activity by assessing the effect of INCB018424 on pre- and post-dose. If the p-STAT3/5 signaling data are sufficiently robust, an exploratory PK/PD analysis will be performed.

"Time of Response " defined as the period of time from the date of first study drug administration until the first objective documentation of response. Clinical response is defined as Complete remission (CR) + Partial remission (PR) + CRp + Hematologic Improvement (HI). Participants in CR must be free of all symptoms related to leukemia and have an absolute neutrophil count (ANC) \>/= 1x10\^9/L, platelet count ./+ 100x10\^9, normal marrow differential (\</= 5% blasts). Partial remission (PR) is CR with 6-25% abnormal cells in the marrow or 50% decrease in marrow blasts. CRp is CR but platelet count \< 100x10\^9/L. HI is defined as for patients with pretreatment hemoglobin less than 11 g/dL, greater than 2 g/dL increase in hemoglobin; for RBC transfusion-dependent patients, transfusion independence.

Exploratory sampling will be done to determine the INCB018424 PK profile. The PK parameters of INB018424 will be summarized using descriptive statistics, and the log-transformed INCB018424 PK parameters will be compared using a 1-factor analysis of variance. The mean values of the PK parameters may be compared to historical data in healthy volunteers to determine if the INCB018424 PK profile is different between patients with hematological malignancies and healthy patients.

Incyte Corporation

M.D. Anderson Cancer Center

The starting dose of INCB018424 will be 25 mg by mouth twice daily.

INCB018424: Starting dose: 25 mg by mouth (po) twice daily for 7 days each week for 4 weeks.

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Farhad Ravandi-Kashani, MD/Professor

Response Rate

INCB018424 PK profile was not done because there was no historical data to compare it to. Data for this Outcome were not collected.

To Determine the Pharmacokinetics (PK) Activity

The lab data was not collected so the analysis could not be done.

To Determine Pharmacodynamics Activity Including the Modulation of Signal Transducer and Activator of Transcription (STAT) Protein Phosphorylation.

Overall Study

Spots Global Cancer Trial Database for jak kinase inhibitor incb018424 phosphate