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

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

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.

Study Overview

• Status: Completed
• Conditions: Lymphoma; Multiple Myeloma; Hodgkin Lymphoma; Hematologic Malignancies
• Intervention / Treatment: Drug: MLN4924

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluation of safety and tolerability	12 months (maximum duration of therapy)

Secondary Outcome Measures

Outcome Measure	Time Frame
Disease response	12 months (maximum duration of therapy)

Collaborators and Investigators

• Sponsor: Millennium Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Faessel HM, Mould DR, Zhou X, Faller DV, Sedarati F, Venkatakrishnan K. Population pharmacokinetics of pevonedistat alone or in combination with standard of care in patients with solid tumours or haematological malignancies. Br J Clin Pharmacol. 2019 Nov;85(11):2568-2579. doi: 10.1111/bcp.14078. Epub 2019 Sep 4.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: July 23, 2008
• First Submitted That Met QC Criteria: July 23, 2008
• First Posted (Estimate): July 25, 2008

Study Record Updates

• Last Update Posted (Estimate): November 18, 2013
• Last Update Submitted That Met QC Criteria: November 15, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms by Site; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Lymphoma; Hematologic Neoplasms; Multiple Myeloma; Neoplasms, Plasma Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Pevonedistat
• Other Study ID Numbers: C15002