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Phase II Study of INCB018424 in Patients With Advanced Hematologic Malignancies


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, Myelodysplastic Syndrome, Chronic Myelogenous Leukemia

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Trial Information

Phase II Study of INCB018424 in Patients With Advanced Hematologic Malignancies


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.


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 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. 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 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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response Rate

Outcome Time Frame:

Patients will be evaluated after each full cycle of therapy (28 days) for response.

Safety Issue:

No

Principal Investigator

Farhad Ravandi-Kashani, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

713/745-0394

Authority:

United States: Food and Drug Administration

Study ID:

2007-0925

NCT ID:

NCT00674479

Start Date:

May 2008

Completion Date:

May 2015

Related Keywords:

  • Acute Myeloid Leukemia
  • Acute Lymphocytic Leukemia
  • Myelodysplastic Syndrome
  • Chronic Myelogenous Leukemia
  • 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
  • Neoplasms
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Myelodysplastic Syndromes
  • Preleukemia
  • Hematologic Neoplasms

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030