An Open-Label, Dose-Escalation, Phase 1 Study of the Oral Form of MLN9708, a Second-Generation Proteasome Inhibitor, in Adult Patients With Relapsed and/or Refractory Multiple Myeloma
Each patient must meet all of the following inclusion criteria to be enrolled in the
- Multiple myeloma diagnosed according to the standard criteria.
- Patients with multiple myeloma who have relapsed following at least 2 lines of
- Patients must have measurable disease.
- ECOG performance status of 0 to 2.
- 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.
- Voluntary written consent.
- Suitable venous access for study-required blood sampling.
Patients meeting any of the following exclusion criteria are not to be enrolled in the
- Peripheral neuropathy > or equal to Grade 2.
- Female patients who are lactating or have a positive serum pregnancy test during the
- 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 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
- 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.
- QTc > 470 milliseconds on a 12-lead 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 MLN9708 including difficulty swallowing.