Dose-Escalation Study of Ponatinib, a FLT3 Inhibitor, With and Without Combination of 5-Azacytidine, in Patients With FLT3-Mutated Acute Myeloid Leukemia (AML)

Leukemia Clinical Trial

Official title: Phase I/II, Dose-Escalation Study of Ponatinib, a FLT3 Inhibitor, With and Without Combination of 5-Azacytidine, in Patients With FLT3-Mutated Acute Myeloid Leukemia (AML)

Status Withdrawn

Clinical Trial Summary

The goal of Part 1 of this clinical research study is to learn if ponatinib alone can help to control FLT3-mutated AML or FLT3-mutated high-risk MDS. The safety of this drug will also be studied.

The goal of Part 2 of this clinical research study is to find the highest tolerable dose of ponatinib in combination with 5-azacytidine and to learn if the highest dose level found can help to control FLT3-mutated AML or FLT3-mutated high-risk MDS. The safety of this combination will also be studied.

Clinical Trial Description

Study Groups:

If participant is found to be eligible to take part in this study, they will be assigned to either Part 1 or Part 2 based on when they join this study.

If participant is enrolled in Part 1, they will receive ponatinib alone for the first cycle. If the doctor thinks it is needed, the dose level may be increased. If the disease does not respond to ponatinib alone, participant will continue on to Part 2 of this study.

Part 2 of this clinical research study will have 2 phases: Phase 1 (dose escalation) and Phase 2 (dose expansion).

In Part 2, participant will be assigned to a study group based on when they join this study. Up to 3 groups of 30 participants will be enrolled in Phase 1 of Part 2, and up to 60 participants will be enrolled in Phase 2.

If participant is enrolled in Phase 1, the dose of ponatinib they receive will depend on when they join this study. The first group of participants will receive the lowest dose level of ponatinib. Each new group will receive a higher dose of ponatinib than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of ponatinib is found.

If participant is enrolled in Phase 2, they will receive ponatinib at the highest dose that was tolerated in Phase 1.

All participants in Part 2 will receive the same dose level of 5-azacytidine.

Study Drug Administration:

Each study cycle is 28 days.

Participant will take ponatinib tablets by mouth 1 time every day while they are on study. Participant should swallow the tablets whole. Participant should not crush them.

If participant is enrolled in Part 2, they will receive 5-azacytidine either by vein over about 1 hour or as an injection under the skin on Days 1-7 of each study cycle or on Days 1-5, 8, and 9 of each study cycle (if the clinic is closed on a weekend).

If the doctor thinks it is needed, the dose level, dosing schedule, or study cycle may be changed and/or delayed. The study doctor will discuss any changes with participant.

Study Visits:

On Day 1 of each cycle (+/- 4 days), participant will have a physical exam.

On Day 1 (+/-1 day) of Cycles 1-3 and then every 3 cycles after that (Cycles 6, 9, 12, and so on), participant will have an EKG.

On Day 1 of Cycle 2 and then every 3 cycles after that, participant will have an ECHO or MUGA performed.

One (1) time each week during Cycles 1-3 and then 1 time every 2-4 weeks after that, blood (about 1 tablespoon) will be drawn for routine tests. Participant may be able to have these blood draws performed at a local lab or clinic that is closer to their home. The results of the testing will be sent to MD Anderson for review.

On Day 28 (+/- 7 days) of Cycles 1, 3, and then every 1-3 cycles after that, participant will have a bone marrow aspiration/biopsy to check the status of the disease.

One (1) time every 3 cycles, if participant can become pregnant, blood (about 1-2 tablespoons) will be drawn for a pregnancy test.

At any time while participant is on study, if the doctor thinks it is needed:

• Blood (about 1-2 tablespoons) will be drawn for routine tests.

• Participant may have a bone marrow aspiration/biopsy to check the status of the disease.

Length of Study:

Participant will receive ponatinib alone or ponatinib and 5-azacytidine for as long as the doctor thinks it is in their best interest. Participant will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if they are unable to follow study directions.

Patient's participation on the study will be over after the follow-up visits.

End-of-Study Visit:

Within 14 days after participant's last dose of study drug(s):

• Participant will have a physical exam.

• Blood (about 2-3 tablespoons) will be drawn for routine tests.

• If the doctor thinks it is needed, participant will have a bone marrow aspirate/biopsy to check the status of the disease.

Follow-Up:

About 30 days after the end-of-study visit, a member of the study staff will call participant to ask if they have had any side effects and/or started any new treatment(s). This call should last about 5 minutes. If the study staff thinks it is needed, participant may also be asked to come into the clinic for a physical exam.

Long-Term Follow-Up:

If the disease appears to be responding to the study drugs, a member of the study staff will call participant every 3-6 months for up to 5 years to ask how they are doing and about any side effects they may be having. Each call should last about 5 minutes. Participant may also be asked to come into the clinic for a physical exam, if the study staff thinks it is needed.

This is an investigational study. 5-azacytidine is FDA approved and commercially available for the treatment of myelodysplastic syndrome (MDS). Ponatinib is commercially available and FDA approved for the treatment of specific groups of chronic myeloid leukemia (CML) participants. Their use in this study is considered investigational. The study doctor can explain how the study drugs are designed to work.

Up to 132 participants will take part in this study. All will be enrolled at MD Anderson. ;

Related Conditions & MeSH terms

• FLT3-Mutated Acute Myeloid Leukemia
• FLT3-Mutated High-Risk Myelodysplastic Syndrome
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

• NCT number: NCT02829840
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: September 2016