Study of Oral Ixazomib in Adult Participants With Relapsed and/or Refractory (RR) Multiple Myeloma

An Open-Label, Dose-Escalation, Phase 1 Study of the Oral Form of Ixazomib (MLN9708), a Second-Generation Proteasome Inhibitor, in Adult Patients With Relapsed and/or Refractory Multiple Myeloma

This study will determine the safety profile, tolerability, and maximum tolerated dose (MTD) and disease response of Ixazomib administered orally in participants with relapsed and/or refractory multiple myeloma.

The drug being tested in this study is ixazomib. Ixazomib is being tested to treat people who have multiple myeloma. This study will look at the safety and efficacy of ixazomib and will enroll approximately 60 participants.

Participants will receive ixazomib by oral capsule twice weekly on Days 1, 4, 8, and 11 of a 21-day cycle. The study will consist of a dose escalation phase to determine the MTD, followed by an expansion phase in which participants will be treated at the MTD.

This multi-center trial will be conducted in the United States. The overall time to participate in this study is 8 years.

Inclusion Criteria:

Each participant must meet all of the following inclusion criteria to be enrolled in the study:

• Multiple myeloma diagnosed according to the standard criteria.
• Participants with multiple myeloma who have relapsed following at least 2 lines of therapy.
• Participants must have measurable disease.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse.
• Male participants who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse.
• Voluntary written consent.
• Suitable venous access for study-required blood sampling.

Exclusion Criteria:

Participants meeting any of the following exclusion criteria are not to be enrolled in the study:

• Peripheral neuropathy greater than or equal to (>=) Grade 2.
• Female participants who are lactating or have a positive serum pregnancy test during the screening period.
• Major surgery within 14 days before the first dose of study drug.
• Infection requiring systemic antibiotic therapy or other serious infection within 14 days before the first dose of study treatment.
• Life-threatening illness unrelated to cancer.
• Diarrhea > Grade 1, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) categorization.
• Systemic antineoplastic or radiation therapy within 14 days of cytotoxic agents within 21 days before the first dose of study treatment.
• Treatment with any investigational products within 21 days before the first dose of study treatment.
• Treatment with any investigational proteasome inhibitor.
• Systemic treatment with prohibited medication.
• Ongoing therapy with corticosteroids greater than 10mg of prednisone or its equivalent per day. Inhaled and topical steroids are permitted.
• Central nervous system involvement.
• Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction within the past 6 months.
• Corrected QT interval (QTc) > 470 milliseconds on a 12-lead electrocardiogram (ECG) obtained during the screening period.
• Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection.
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol.
• Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption of tolerance of ixazomib including difficulty swallowing.