Phase I-II Study of Ruxolitinib (INCB18424) for Patients With Chronic Myeloid Leukemia (CML) With Minimal Residual Disease While on Therapy With Tyrosine Kinase Inhibitors
Study Drug Administration:
If you are found to be eligible to take part in this study, you will continue receiving the
same TKI at the dose you had been receiving for the last 6 months.
You will also receive ruxolitinib by mouth 1 or 2 times daily. The dose level and how often
you take the drug will depend on when you enter the study. The study staff will give you
more detailed instructions about how often you will take the drug and what you should do if
you vomit or miss a dose of study drug.
In the first part of the study, you will be assigned to a dose level of ruxolotinib based on
when you join this study. Up to 3 dose levels of ruxolitinib will be tested. At least 3
participants will be enrolled at each dose level. The first group of participants will
receive the lowest dose level. Each new group will receive a higher dose than the group
before it, if no intolerable side effects were seen. This will continue until the highest
tolerable dose of ruxolotinib is found. This is called the Dose Escalation Group.
After the highest tolerated dose has been found, an extra 30 participants will receive
ruxolotinib at that dose level. This is called the Dose Expansion Group.
Each study cycle is 4 weeks.
At every visit, you will be asked about any side effects you may have had and to list any
drugs you may be taking.
Every 1-2 weeks for 8 weeks, then every 3 months, blood (about 1 teaspoon) will be drawn for
Every 2-4 weeks for 8 weeks, then every 3 months, blood (about 1 teaspoon) will be drawn to
test your kidney and liver function.
Before each cycle for the first 3 cycles, then every 3-6 cycles for the first year, then
every 6-12 cycles after that, blood (about 1 tablespoon) drawn for molecular testing.
Every 3-6 months for the first year, then every 6-12 months after that you will have a bone
marrow aspirate to check the status of the disease.
Every 3 months (+/- 1 month) for the first 6 months, then every 6-12 months after that, you
will have a complete physical exam.
Length of Study:
You may continue taking the study drug for up to 2 years 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, if intolerable side effects occur, or if you are unable to follow study directions.
Your participation on the study will be over after you have completed both the
end-of-treatment and follow-up visits.
After your last dose of study drug, you will be called or you will come in to the clinic
within 30 days and you will be asked about any side effects and/or symptoms you may be
having. If you are contacted by phone, the call should last about 2-3 minutes.
If you end your participation on this study because the disease has gotten worse, blood
(about 1 tablespoon) will be drawn for molecular testing every 4 weeks for the first 6
months after you stop study treatment, then every 6 months for the next year, then every 6
weeks after that.
If necessary, some of these tests may be done by your home physician and the results faxed
to MD Anderson for review.
If you have severe side effects from the study drug, the study doctor may decide to reduce
and/or stop drug dosing until your side effects improve. If the doctor thinks it is in you
best interest, your dose may be increased.
If all tests to find the disease are completely negative, you may have the option to stop
both the TKI and ruxolitinib. If this happens, your doctor will monitor you closely to
check for any evidence the disease has returned. If this is the case, treatment with one or
both drugs may be re-started at the same doses you were taking before you stopped.
You must return any unused and/or expired study drug to MD Anderson at each study visit.
This is an investigational study. TKIs are approved for the treatment of CML and are given
as part of your standard of care, even if you do not participate in this study. Ruxolitinib
is FDA approved and commercially available for the treatment of patients with myelofibrosis.
The combination of these drugs to treat CML is investigational.
Up to 48 patients will take part in this study. All will be enrolled at MD Anderson.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD) for Ruxolitinib and Tyrosine Kinase Inhibitors (TKIs).
MTD is highest dose level at which 6 patients were treated and at most 1 patient experienced a dose limiting toxicity (DLT).
Jorge Cortes, MD
UT MD Anderson Cancer Center
United States: Food and Drug Administration
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