Slow Accrual

The goal of this clinical research study is to learn if ixazomib can prevent AML or MDS from coming back in patients who are in remission. The safety of this drug will also be studied.

Study Drug Administration:

Each study cycle is 28 days.

If you are found to be eligible to take part in this study, you will take ixazomib capsules on Days 1, 8 and 15 of each cycle. Ixazomib capsules should be swallowed whole, with water, on an empty stomach (take the dose at least 1 hour before or 2 hours after a meal).

If you miss a dose, take it as soon as you remember, as long as the next scheduled dose is more than 3 days away. If you vomit after taking a dose, do not make up the dose but continue with the next scheduled dose as planned.

You may receive the study drug for up to 12 cycles. If the doctor thinks it is in your best interest, you may be able to continue taking the study drug beyond Cycle 12.

Study Visits:

On Day 1 of each cycle (+/- 1 day):

• You will have a physical exam.
• Blood (about 2-3 teaspoons) will be drawn for routine tests.

On Days 8 and 15 of Cycle 1, blood (about 2-3 teaspoons) will be drawn for routine tests.

Every third cycle, you will have a bone marrow aspiration and/or biopsy to check the status of the disease.

Length of Study:

You may continue taking the study drug for 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 the end-of-study visit.

End-of-Study Visit:

After your last dose of study drug, you will return to the clinic for an end-of-study visit.

• Blood (about 2-3 tablespoons) will be drawn for routine tests.
• You will have a bone marrow aspirate and/or biopsy to check the status of the disease.

This is an investigational study. Ixazomib is not FDA-approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the study drug is designed to work.

Up to 40 participants will be enrolled in this study. All will take part at MD Anderson.

Inclusion Criteria:

1. Male or female patients 18 years of age or older.
2. Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
3. Female patients who: Are postmenopausal for at least 1 year, OR Are surgically sterile, OR If they are of childbearing potential, agree to practice 2 effective methods of contraception, from the time of signing the informed consent through 90 days after the last dose of study drug, OR Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.) Male patients, even if surgically sterilized, must agree to one of the following: Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject.
4. Patients must have a history of de novo or therapy-related AML (defined by World Health Organization (WHO) classification of >/= 20% bone marrow blasts) or high-risk MDS (defined by International Prostate Symptom Score (IPSS) or IPSS-R)
5. 5. Patients must be in a documented complete response/incomplete blood count recovery (CR/CRi) from either their front-line or first salvage therapy as evidenced by </= 5% bone marrow blasts and absence of extramedullary disease. (For patients with prior MDS who then transformed to AML, therapy received for MDS is not considered prior therapy for AML)
6. Patients should have received at least 2 cycles of induction therapy or 1 induction and 1 consolidation cycle, OR patient should be considered to have completed all planned chemotherapy, OR patient is considered to be unable, unfit or unwilling to receive additional chemotherapy.
7. Eastern Cooperative Oncology Group (ECOG) performance 0, 1, or 2.
8. Patients must meet the following clinical laboratory criteria: - Absolute neutrophil count (ANC) >/= 500/mm3 and platelet count >/= 50,000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment - Total bilirubin </= 1.5 x the upper limit of the normal range (ULN). - Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)</= 3 x ULN. - Calculated creatinine clearance >/= 30 mL/min

Exclusion Criteria:

1. Female patients who are lactating or have a positive serum pregnancy test during the screening period.
2. Failure to have fully recovered (ie, </= Grade 1 toxicity) from the reversible effects of prior chemotherapy.
3. Major surgery within 14 days before enrollment.
4. Radiotherapy within 14 days before enrollment. If the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the MLN9708.
5. Known central nervous system involvement
6. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.
7. Evidence of current uncontrolled cardiovascular conditions, including sustained hypertension (SBP >150mmHg on two or more readings one week apart without normalization in between), clinically significant uncontrolled cardiac arrhythmias, symptomatic Class III-IV New York Heart Association (NYHA) congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
8. Systemic treatment, within 7 days, or the half life of the treatment, whichever is longer before the first dose of MLN9708, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of cytochrome P CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort.
9. Ongoing or active systemic infection, history of hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive.
10. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
11. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
12. Known GI disease or GI procedure that is expected to interfere with the oral absorption or tolerance of MLN9708 including difficulty swallowing. As determined by the investigator.
13. Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
14. Patient has >/= Grade 3 peripheral neuropathy, or Grade 2 with pain on clinical examination during the screening period.
15. Administration of other investigational agents for the treatment of AML/MDS within 21days (or 5 times the terminal half life of the investigational treatment whichever is longer) of the start of this trial and throughout the duration of this trial.
16. At the time of registration, stem cell transplantation is not planned within the next 3 months.

Adverse events reported during each treatment course, an average of one year . Overall period: May 2015 to March 2016.