The primary objective of the study is to determine the maximum tolerated dose (MTD) of CEP-18770 in combination with lenalidomide and dexamethasone in participants with relapsed or refractory multiple myeloma.

After cycle 1, the start of treatment in each cycle may occur within a 3-day window. In addition, after cycle 2, the start of treatment in cycle 3 may be delayed by 1 week if, in the opinion of the investigator, the delay is warranted. If a participant cannot receive 75% of the planned dose for any of the 3 agents (missing more than 1 dose of CEP-18770, or more than 5 doses of lenalidomide [either consecutively or separately], or more than 1 dose of dexamethasone [either consecutively or separately]), due to a drug-related adverse event, the event will be considered a dose limiting toxicity (DLT), even if the grade of toxicity is lower than specified DLT determination. Participants will receive intravenous (IV) CEP-18770 on Days 1, 8, and 15, oral lenalidomide on days 1 through 21, and oral dexamethasone on days 1, 8, 15, and 22 of each 28-day cycle. Treatment with all 3 drugs will continue for up to 12 cycles (approximately 11 months), or until disease progression or intolerable toxicities. Participants experiencing clinical benefit may continue to receive additional treatment at the investigator's discretion and following sponsor notification. In part 2 of the study, participants will receive CEP-18770 as a slow IV bolus (approximately 1 milliliter per minute) at the maximum tolerated dose on days 1, 8, and 15 of every 28-day cycle. Participants who complete or discontinue study drug treatment and whose disease has not progressed will have study visits every 7-9 weeks during follow-up until disease progression, death, or until they have been monitored for 1 year after the first administration of study drug, whichever occurs first.

Inclusion Criteria:

• The participant is a man or woman at least 18 years of age with documented multiple myeloma.
• The participant has relapsed or progressive disease after receiving at least 1 previous chemotherapy treatment but no more than 5 previous therapies.
• The participant has measurable disease defined as 1 of the following:
• serum M-protein 0.5 grams (g)/deciliter (dL) or greater
• urine M-protein 200 mg/24 hours or greater
• The participant has a life expectancy of more than 3 months.
• Written informed consent is obtained.
• The participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• The participant has adequate hepatic and renal function and hematologic assessments as specified by the study protocol
• The participant has been independent of support with granulocyte-colony stimulating factor (G-CSF) or granulocyte macrophage-colony stimulating factor (GM-CSF) for more than 1 week at the time of screening.
• The participant has been independent of platelet transfusions for 1 week at the time of screening.
• The participant may have received an allogeneic and/or autologous transplant.
• The participant must agree to register into the mandatory risk evaluation and mitigation program for receiving lenalidomide if required by local regulations.
• Agreement by women of childbearing potential (not surgically sterile or 24 months postmenopausal) to use 2 medically accepted methods of contraception and must agree to continue use of these methods from 4 weeks prior to treatment to 4 weeks after treatment. Acceptable methods of contraception include at least one highly effective method (for example, intrauterine device [IUD], non-combination hormonal contraception, tubal ligation, or partner's vasectomy) and one additional method (for example, latex condom, diaphragm, or cervical cap).
• Agreement by men who are sexually active with a woman of childbearing potential (as defined in the criterion above), to use a condom during any sexual contact for the duration of the study and for 4 weeks after the last administration of study drug. This requirement applies even if the man has had a vasectomy.
• The participant may not donate blood, semen or sperm while taking lenalidomide or for 4 weeks after the last administration of lenalidomide.
• The participant may not breastfeed while taking lenalidomide or for 4 weeks after the last administration of lenalidomide.

Exclusion Criteria:

• The participant has nonmeasurable multiple myeloma, defined as less than 0.5 g/dL M-protein in the serum, and less than 200 mg/24 hours M-protein in the urine.
• The participant could not tolerate previous lenalidomide or low-dose dexamethasone treatment.
• The participant had previous treatment with CEP-18770.
• The participant has POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy or monoclonal proliferative disorder, and skin changes [increased skin pigment, increased body hair, thickening of the skin, whitening of the nails, etc]).
• The participant has plasma cell leukemia or primary amyloidosis.
• The participant received chemotherapy with approved or investigative anticancer therapeutics within 3 weeks before the first dose of study drug.
• The participant received radiation therapy or immunotherapy within 4 weeks or localized radiation therapy within 1 week prior to the first dose of study drug.
• The participant had major surgery within 3 weeks before the first dose of study drug.
• The participant has congestive heart failure (New York Heart Association Class III to IV) or had symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within the last 6 months.
• The participant had an acute infection requiring systemic antibiotics, antiviral agents, or antifungal agents within 2 weeks before the first dose of study drug.
• The participant has a known or suspected human immunodeficiency virus (HIV) infection, acute or chronic hepatitis B virus or hepatitis C virus on the basis of their medical history.
• The participant has myelodysplastic or myeloproliferative syndrome.
• The participant has significant neuropathy (at least grade 2, or grade 1 with pain).
• The participant is a pregnant or lactating woman.
• The participant has known hypersensitivity to CEP-18770, lenalidomide, thalidomide, dexamethasone, mannitol, or hydroxypropyl betadex.
• The participant received glucocorticoid therapy (prednisone >10 mg/day orally or equivalent) within the last 2 weeks prior to the first dose of study drug.
• The participant has a history of malignancy, other than multiple myeloma, within the last 5 years excluding adequately treated curable disease or indolent disease that is not likely to require therapy during the conduct of the study.
• The participant has known central nervous system (CNS) involvement.