Study of MLN4924, a Novel Inhibitor of Nedd8 Activating Enzyme, in Adult Patients With Lymphoma or Multiple Myeloma
Study Details
Study Description
Brief Summary
This is an open-label, multicenter, phase 1, dose escalation study of MLN4924 in adult patients with lymphoma or multiple myeloma. The patient population will consist of adults with 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.
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 MLN4924 |
Drug: MLN4924
Intravenous dose 100 mg/m2 on a Days 1,4,8,11 schedule within a 21-day treatment cycle. Treatment may continue until disease progression or unacceptable toxicity develops.
|
Outcome Measures
Primary Outcome Measures
- Evaluation of safety and tolerability [12 months (maximum duration of therapy)]
Secondary Outcome Measures
- Disease response [12 months (maximum duration of therapy)]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
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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.
- 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.
- As of Protocol Amendment 7, tumor that is evaluable by radiography or clinical evaluations.
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Suitable venous access for the conduct of blood sampling for MLN4924
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Adequate Organ Function
Exclusion Criteria:
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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).
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Treatment with corticosteroids within 7 days preceding first dose of study treatment.
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Prior treatment with radiation therapy involving >25% of bone marrow; Any radiotherapy within 14 days before first dose of study treatment.
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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 study.
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Patients requiring Coumadin who cannot be switched to a low molecular weight heparin should not be considered for this study.
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Absolute neutrophil count less than 1,000/mm3; platelet count less than 75,000/mm3.
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Calculated creatinine clearance less than or equal to 50 mL/minute.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Winship Cancer Institute | Atlanta | Georgia | United States | 30322 |
| 2 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263 |
Sponsors and Collaborators
- Millennium Pharmaceuticals, Inc.
Investigators
- Study Director: Medical Monitor, Millennium Pharmaceuticals, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- C15002