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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00722488
First received: July 23, 2008
Last updated: November 15, 2013
Last verified: November 2013
  Purpose

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 Intervention Phase
Hematologic Malignancies
Multiple Myeloma
Lymphoma
Hodgkin Lymphoma
Drug: MLN4924
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Evaluation of safety and tolerability [ Time Frame: 12 months (maximum duration of therapy) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Disease response [ Time Frame: 12 months (maximum duration of therapy) ] [ Designated as safety issue: No ]

Enrollment: 56
Study Start Date: June 2008
Study Completion Date: September 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00722488

Locations
United States, Georgia
Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00722488     History of Changes
Other Study ID Numbers: C15002
Study First Received: July 23, 2008
Last Updated: November 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases

ClinicalTrials.gov processed this record on October 22, 2014