Study of MLN4924, a Novel Inhibitor of Nedd8 Activating Enzyme, in Adult Patients With Lymphoma or Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00722488
• Other study ID #: C15002
• Status: Completed
• Phase: Phase 1
• First received: July 23, 2008
• Last updated: November 15, 2013
• Start date: June 2008
• Est. completion date: September 2013

Study information

• Verified date: November 2013
• Source: Millennium Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: September 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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 evaluations.

• Suitable venous access for the conduct of blood sampling for MLN4924

• Adequate Organ Function

Exclusion Criteria:

• 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 study.

• 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.

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hematologic Malignancies
• Hodgkin Disease
• Hodgkin Lymphoma
• Lymphoma
• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

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.

Locations

Country	Name	City	State
United States	Winship Cancer Institute	Atlanta	Georgia
United States	Roswell Park Cancer Institute	Buffalo	New York

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of safety and tolerability		12 months (maximum duration of therapy)	Yes
Secondary	Disease response		12 months (maximum duration of therapy)	No