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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

Phase 1/Phase 2
18 Years
Not Enrolling

Thank you

Trial Information

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.

Study Visits:

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
routine tests.

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.

End-of-Treatment 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.

Other Information:

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.

Inclusion Criteria:

1. Patients 18 years or older with Philadelphia chromosome (Ph)-positive or
BCR/ABL-positive CML (as determined by cytogenetics, FISH, or PCR).

2. Patients must be on continuous TKI therapy for management of their CML. Any
commercially available and FDA- approved TKI can be used, i.e., imatinib mesylate
(IM), nilotinib (NIL) or dasatinib (DAS). Patients may be receiving TKI at entry in
the frontline or salvage setting, including patients currently on imatinib after
alpha-interferon failure or on dasatinib or nilotinib after failure to prior therapy
including imatinib.

3. Patients must have received the current TKI for at least 18 months and not have
increased their dose in the last 6 months.

4. For the phase I portion of the study, patients may be included without a CCyR
provided they remain in chronic or accelerated phase CML and have at least a CHR. For
the Phase II portion of the study patients must be in complete cytogenetic remission
(CCyR), regardless of the stage of disease they had at the time they started therapy
with TKI.

5. Patients must have detectable BCR-ABL transcript levels meeting at least 1 of the
following criteria: Patient has never achieved a major molecular response (MMR, as
defined by a BCR-ABL/ABL 0.28 in the MDACC molecular diagnostic laboratory), & transcript levels have shown in
at least 2 consecutive measures separated by at least 1 month to have increased by
any value; or achieved a major molecular response which has been lost, with an
interim increase in transcript levels by at least one-log, confirmed in two
consecutive analyses separated by at least 1 month; or patient has received therapy
for at least 2 years & lacks a sustained major molecular response; or patient has
received therapy for at least 5 years & lacks a sustained complete molecular response
(CMR, defined as transcript levels still detectable in the MDACC molecular diagnostic

6. Patients must not have had a known interruption of TKI therapy of greater than 21
consecutive days or for a total of 6 weeks in the 6 months prior to enrollment.

7. Patients must be able to understand and sign an informed consent indicating that they
are aware of the investigational nature of this study in keeping with the
institutional policies.

8. ECOG performance status
9. Adequate organ function defined as: bilirubin <2x upper limit of normal (ULN) (unless
associated with Gilbert's syndrome), and ALT or AST <2.5x ULN.

10. ANC >/=1 x10(9)/L and platelets >/=100 x10(9)/L.

11. Serum creatinine < 1.5 mg/dL or creatinine clearance greater or equal than 60 cc/min
as defined by the Cockcroft-Gault Equation: Males(mL/min):(140-age)*IBW(kg) /
72*(serum creatinine (mg/dl)); Females (mL/min):0.85*(140-age)*IBW(kg) / 72*(serum
creatinine (mg/dl)).

12. Women of childbearing potential should be advised to avoid becoming pregnant while on
therapy with Ruxolitinib and for 30 days after the last dose and practice effective
methods of contraception. Men should be advised not to father a child while receiving
treatment with Ruxolitinib and for 30 days after the last dose. Effective methods of
contraception for this study include barrier methods (e.g., condoms, diaphragm);
spermicidal jelly or foam; oral, depo provera, or injectable hormonal contraceptives;
intrauterine devices; tubal ligation; and abstinence.

Exclusion Criteria:

1. For the phase I portion of the study, patients in blast phase. For the phase II
portion of the study, patients in accelerated or blast phase.

2. Patients receiving any other investigational agents.

3. Patients who are pregnant or breast-feeding.

4. Patients with clinically significant heart disease (NYHA Class III or IV).

5. Patients with QTc > 480 msec.

6. Patients taking a potent CYP3A4 inhibitor that cannot be changed to an alternate

7. Known or suspected hypersensitivity to ruxolitinib.

8. Patients with advanced malignant hepatic tumors.

9. Patients with known active hepatitis B or C, or HIV infection.

10. Patients with other medical conditions or concomitant medications that in the opinion
of the principal investigator may interfere with the therapeutic treatment.

Type of Study:


Study Design:

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

Outcome Measure:

Maximum Tolerated Dose (MTD) for Ruxolitinib and Tyrosine Kinase Inhibitors (TKIs).

Outcome Description:

MTD is highest dose level at which 6 patients were treated and at most 1 patient experienced a dose limiting toxicity (DLT).

Outcome Time Frame:

3 months

Safety Issue:


Principal Investigator

Jorge Cortes, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

October 2013

Completion Date:

Related Keywords:

  • Leukemia
  • Leukemia
  • Chronic Myeloid Leukemia
  • CML
  • Minimal Residual Disease
  • Philadelphia chromosome
  • (Ph)-positive
  • BCR/ABL-positive
  • Ruxolitinib
  • Jakafi
  • INCB018424
  • INC424
  • TKI
  • Tyrosine kinase inhibitor
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Neoplasm, Residual



UT MD Anderson Cancer Center Houston, Texas  77030