An Open-Label, Phase I/II Study of Nilotinib (Tasigna) and MEK-162 (ARRY-162) Used in Combination for Patients With Refractory or Advanced Chronic Myeloid Leukemia and Philadelphia Positive Acute Leukemia (Protocol CAMN107AUS41T)

Clinical Trial Summary

The goal of this clinical research study is to find the highest tolerated dose of the combination of nilotinib and MEK-162 that can be given to patients with CML or acute leukemia. Researchers also want to learn if the drug combination can help to control the disease. The safety of the drug combination will also be studied.

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 5 groups of up to 6 participants will be enrolled in Phase 1 of the study, and up to 60 participants will be enrolled in Phase 2.

If you are enrolled in Phase 1, the dose of nilotinib and MEK-162 you receive will depend on when you joined this study. The first group of participants will receive the starting dose combination level. The next group will receive a higher dose of MEK-162 than Group 1, if no intolerable side effects were seen. If intolerable side effects are seen, the next group may receive a lower dose level of nilotinib and/or MEK-162. This will continue until the highest tolerable combination dose is found.

If you are enrolled in Phase 2, you will receive nilotinib and MEK-162 at the highest dose that was tolerated in Phase 1.

Study Treatment:

You will take nilotinib and MEK-162 two times every day by mouth.

Participants enrolled in Phase 1 of the study will start taking MEK-162 on Day 1 and nilotinib on Day 2.

Participants in Phase 2 of the study will be divided in 2 groups: one group will start MEK-162 on Day 1 and nilotinib on Day 2, while the other group will start MEK-162 on Day 1 and nilotinib on Day 8. You will be placed in a Phase 2 treatment group based on the characteristics of your disease type.

You will be given a drug diary and asked to write down what time you take the study drugs every day. Bring in any unused study drugs and bottles to each study visit.

Each cycle is 28 days.

If the disease does not appear to get better after 1 or 3 cycles, you may be able to receive a higher dose of the study drug as long as you are not already receiving the highest dose planned for this study. The study doctor will tell you if you can receive a higher dose.

Study Visits:

On Days 1 and 8 of Cycle 1:

- You will have a physical exam.

- Blood (about 2-3 tablespoons) and urine will be collected for routine tests.

- You will have an EKG.

At the end of Cycle 1:

- You will have a physical exam.

- Blood (about 2-3 tablespoons) and urine will be collected for routine tests.

- You will have an EKG and either a MUGA scan or an ECHO.

- You will complete a questionnaire about how you are feeling.

- If the doctor thinks it is needed, you will have a bone marrow aspirate to check the status of the disease.

At the end of Cycles 2, 3, and every 3 cycles after that (6, 9, 12, and so on):

- You will have a physical exam.

- Blood (about 2-3 tablespoons) and urine will be collected for routine tests.

- You will have an EKG.

- You will complete a questionnaire about how you are feeling.

At the end of Cycles 2, 3, 6, 9, and 12, blood (about 3-4 tablespoons each time) will be drawn for tests to check how the disease is responding to therapy. If the doctor thinks it is needed, these tests may be performed more often.

Every 8-12 weeks, you will have a MUGA scan or an ECHO.

You will have an eye exam by an eye doctor at the end of Cycles 2, 3, 6, 9, and 12, and then every 3 months after that until the End of Study Visit.

You will have blood draws and/or bone marrow aspirations at any time that the doctor thinks it is needed while you are on study.

Length of Study:

You can take up to 12 cycles of nilotinib and MEK-162 on study. If the disease responds a certain way (called a hematological response) while you are on study, you may be able to continue taking the study drugs longer than 12 months, as long as the doctor thinks you are benefiting from the treatment. Even if the disease has not responded in this way, you may be able to continue taking the study drugs if 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 the follow-up visits.

End-of-Study Visit:

If you come off study before the end of Cycle 12, the following tests and procedures will be performed:

- You will have a physical exam.

- Blood (about 2-3 tablespoons) and urine will be collected for routine tests.

- You will have an EKG and either an ECHO or a MUGA scan.

- You will have an eye exam by an eye doctor.

- You will complete a questionnaire about how you are feeling.

- If the doctor thinks it is needed, you will have a bone marrow aspirate to check the status of the disease.

If you come off study at the end of Cycle 12, you will not have the End of Study visit.

Follow-Up:

You will be called about 30 days after you go off study and asked if you have had any side effects and/or any new treatment(s). This call will last about 5 minutes.

This is an investigational study. Nilotinib is FDA approved and commercially available to treat CML and philadelphia-positive acute leukemia. MEK-162 is not FDA approved or commercially available. It is currently being used for research purposes only. The combination of nilotinib and MEK-162 to treat CML and Philadelphia-positive acute leukemia is investigational. The study doctor can explain how the study drugs are designed to work.

Up to 90 patients will take part in this study. All will be enrolled at MD Anderson Cancer Center. ;

Study Design

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid