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

NCT ID: NCT00722488

Last Updated: 2013-11-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

56 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-06-30

Study Completion Date

2013-09-30

Brief Summary

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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.

Detailed Description

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Conditions

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Hematologic Malignancies Multiple Myeloma Lymphoma Hodgkin Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

MLN4924

Group Type EXPERIMENTAL

MLN4924

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Monitor

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

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Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 31355467 (View on PubMed)

Other Identifiers

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C15002

Identifier Type: -

Identifier Source: org_study_id