Study Evaluating the Safety and Tolerability of Weekly Dosing of Oral IXAZOMIB in Adult Patients With Relapsed and Refractory Multiple Myeloma

The drug being tested in this study is called ixazomib citrate (MLN9708). Ixazomib citrate is
being tested for people who have multiple myeloma who have relapsed after treatment or become
unresponsive to treatment.

This study will determine the maximum tolerated dose (MTD) of ixazomib citrate using a dose
escalation scheme. Once MTD is established, participants will be enrolled at MTD into one of
the 4 expansion cohorts to characterize the safety, tolerability and efficacy of MLN9708.
Blood samples for safety labs, hematology, serum chemistry and pharmacokinetic evaluations
will be obtained at the timepoints specified. Disease response assessment is to be performed
on the first day of every other cycle beginning with Cycle 3.

The study will enroll approximately 60 patients. All participants will receive treatment with
ixazomib citrate. This multi-center trial will be conducted in the United States. The overall
time to participate in this study is up to 60 days, and participants will make 12-16 visits
to the clinic for study procedures.

Inclusion Criteria:

Each patient must meet all of the following eligibility criteria to be enrolled in the
study:

- Adult patients with multiple myeloma who have relapsed following at least 2 lines of
therapy.

- Patients must have measurable disease.

- Appropriate functional status, including the recovery from the effects of prior
antineoplastic therapy, and acceptable organ function as described in the protocol.

- Female patients who are post menopausal, surgically sterile, or agree to practice 2
effective methods of contraception or abstain from heterosexual intercourse.

- Male patients who agree to practice effective barrier contraception or agree to
abstain from heterosexual intercourse.

- Willing and able to give written informed consent.

- Suitable venous access for study-required blood sampling.

Exclusion Criteria:

- Peripheral neuropathy that is greater or equal to Grade 2.

- Major surgery or, serious infections, or infections that required systemic antibiotic
therapy within 14 days before the first dose of study drug.

- Life-threatening illness unrelated to cancer.

- Diarrhea that is greater than Grade 1 as outlined in the protocol

- Systemic antineoplastic or radiation therapy within 14 days or cytotoxic agents, or
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 medications that are outlined in the protocol
within 14 days of study treatment.

- Ongoing therapy with corticosteroids greater than 10mg of prednisone or its equivalent
per day.

- 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.

- Known human immunodeficiency virus (HIV) positive, hepatitis B surface
antigen-positive status, or known or suspected active hepatitis C infection.

- 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.