Phase I/II, Study of Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) + Sorafenib in Acute Myeloid Leukemia

Leukemia Clinical Trial

Official title: Phase I/II, Study of Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) + Sorafenib in Acute Myeloid Leukemia

Status Completed

Clinical Trial Summary

There are 2 parts to this study: Part 1 (dose escalation) and Part 2 (dose expansion).

The goal of Part 1 of this clinical research study is to find the highest tolerated dose of the combination of selinexor (KPT-330) and sorafenib (Nexavar) that can be given to patients with FLT3-ITD and -D835 mutated acute myeloid leukemia (AML) or FLT3-mutated high-risk myelodysplastic syndrome (MDS).

The goal of Part 2 of this study is to learn if the dose found in Part 1 can help to control the disease.

The safety of the drug combination will also be studied in both parts of this study.

This is an investigational study. Sorafenib is FDA approved and commercially available to treat hepatocellular cancer. Selinexor is not FDA approved or commercially available. It is currently being used for research purposes only. The combination of selinexor and sorafenib to treat FLT3-mutated AML and high-risk MDS is investigational.

The study doctor can explain how the study drugs are designed to work.

Up to 52 participants will take part in this study. All will be enrolled at MD Anderson.

Clinical Trial Description

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 3 groups of up to 6 participants will be enrolled in Part 1 of the study, and up to 40 participants will be enrolled in Part 2.

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

If you are enrolled in Part 2, you will receive selinexor and sorafenib at the highest tolerable combination dose or most effective combination dose found in Part 1.

Study Drug Administration:

Each study cycle is 28 days. However, the study cycles may be 3-12 weeks long, depending on if/how the disease responds to the treatment, how your bone marrow reacts to treatment, and what the doctor thinks is in your best interest.

You will take selinexor tablets by mouth 2 times each week (Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday) for 3 weeks. You must take your dose of selinexor within 30 minutes after eating, with at least 4 ounces of fluids (either water, milk, juice, and so on). You must swallow the tablets whole. Do not crush them. If the powder comes into contact with your skin, you may have an increased chance of skin-related side effects.

You will take sorafenib by mouth 2 times a day, every day. Depending on how the disease responds to the study drugs, the number of days you receive the study drug may change. Your doctor will discuss this with you. You must take your dose of sorafenib at least 1 hour before or 1 hour after eating.

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

Study Visits:

On Day 1 of Cycles 1-4 and then every 1-3 cycles after that:

• You will have a physical exam.

• You will have an EKG.

The study doctor will tell you how often you will have these tests after Cycle 4.

One time each week during Cycles 1-3, blood (about 1 tablespoon) will be drawn for routine tests. After Cycle 3, you will have this blood draw 1 time every 2-4 weeks. If the doctor thinks it is needed, blood may need to be drawn more often or more than 1 tablespoon of blood may need to be drawn.

After Cycle 1, you may be able to have these blood draws performed at a local lab or clinic that is closer to your home. The results of the testing will be sent to MD Anderson for review. The study doctor or study staff will discuss this option with you.

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

Every 3 months (+/- 14 days), if you can become pregnant, blood (about 1-2 tablespoons) or urine will be collected for a pregnancy test.

If you stay on study for more than 6 months and you are not having side effects, you may have some of the above tests more or less often. The study doctor will discuss this with you.

Length of Study:

You may continue taking the study drugs for as long as the study doctor thinks it is in your best interest. You will no longer be able to take the study drugs 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 stop taking the study drugs before the end of Cycle 24:

• You will have a physical exam.

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

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

Follow-Up:

About 30 days (+/- 7) after your last dose of study drugs, you will have a physical exam. You may have this exam at MD Anderson or a local clinic near your home. If you have this exam at a local clinic, the results of the exam will be sent to MD Anderson for review.

If you cannot come to MD Anderson or a local clinic, you will be called by a member of the study staff and asked if you have had any side effects and/or started any new treatment(s). This call should last about 5 minutes.

Long-Term Follow-Up:

If the disease appears to get better and you are responding well to the study drug, you will return to MD Anderson every 3-6 months for up to 5 years after your last dose of study drugs for the study staff to check how you are doing.

If you cannot return to MD Anderson for these visits, you may be called by a member of the study staff. The call should last about 10 minutes. ;

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

• NCT number: NCT02530476
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 8, 2015
• Completion date: April 8, 2019