An Open-Label, Dose-Escalation, Phase 1 Study Evaluating the Safety and Tolerability of Weekly Dosing of the Oral Form of MLN9708, a Second-Generation Proteasome Inhibitor, in Adult Patients With Relapsed and Refractory Multiple Myeloma
Each patient must meet all of the following eligibility criteria to be enrolled in the
- Adult patients with multiple myeloma who have relapsed following at least 2 lines of
- 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.
- Peripheral neuropathy that is greater or equal to Grade 2.
- Major surgery or, serious infections, or infections that required systematic
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
- 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 MLN9708 including difficulty swallowing.