An Open-Label, Dose Escalation, Phase I Study of MLN4924, a Novel Inhibitor of Nedd8 Activating Enzyme, in Adult Patients With Lymphoma or Multiple Myeloma
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Patients must have a confirmed diagnosis of lymphoma (Waldenstrom's macroglobulinemia
is permitted) or multiple myeloma that is relapsed and/or refractory after at least 2
prior standard chemotherapeutic regimens and for which no curative option exists.
1. As of Protocol Amendment 7, patients in the expansion cohort, Schedule E, must
specifically have Hodgkin lymphoma, DLBCL-GCB subtype, DLBCL-non-GCB subtype, or
Mantle Cell Lymphoma (MCL). Patients with multiple myeloma will no longer be
evaluated as a part of this study.
- Tumor that is evaluable by radiography, serum or urine electrophoresis (for patients
with multiple myeloma), or clinical evaluations.
1. As of Protocol Amendment 7, tumor that is evaluable by radiography or clinical
- Suitable venous access for the conduct of blood sampling for MLN4924
- Adequate Organ Function
- Systemic antineoplastic therapy within 21 days preceding first dose of study
treatment, or rituximab therapy within 2 months preceding first dose of study
treatment (unless there was evidence of PD since their last dose of rituximab).
- Treatment with corticosteroids within 7 days preceding first dose of study treatment.
- Prior treatment with radiation therapy involving >25% of bone marrow; Any
radiotherapy within 14 days before first dose of study treatment.
- Treatment with CYP3A inducers within 14 days before the first dose of MLN4924.
Moderate and strong CYP3A inhibitors and CYP3A inducers are not permitted during the
- Patients requiring Coumadin who cannot be switched to a low molecular weight heparin
should not be considered for this study.
- Absolute neutrophil count less than 1,000/mm3; platelet count less than 75,000/mm3.
- Calculated creatinine clearance less than or equal to 50 mL/minute.