Study of MLN9708 as Maintenance Therapy for Patients With Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS) in Remission
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes
Intervention: Ixazomib
Intervention description: 4 mg by mouth on Days 1, 8 and 15 of each 28-day cycle.
Intervention MeSH terms: Ixazomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Leukemia; Acute myeloid leukemia; AML; High-risk myelodysplastic syndrome; MDS; Ixazomib; MLN9708

Summary:

      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.
    

Eligibility criteria:

        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             be withdrawn by the patient at any time without prejudice to future medical care.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.