Advanced Nonhematologic MalignanciesPhase 1NCT00677170
Study of MLN4924 in Adult Patients With Nonhematologic Malignancies
A Phase 1 study testing MLN4924 in people with Advanced Nonhematologic Malignancies, run by Millennium Pharmaceuticals, Inc. at 3 sites in United States.
Trial summary
This study is an open-label, multicenter, Phase 1, dose escalation study of MLN4924 in adult patients with nonhematologic malignancies. This study will be the first to administer MLN4924 in humans. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Nonhematologic Malignancies
- What is being tested?
- MLN4924
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 3 sitesUnited States
- Study dates
- Apr 2008to Dec 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients 18 years or older
- Eastern Cooperative Oncology Group performance status 0-2
- Patients must have a diagnosis of a nonhematologic malignancy for which standard curative, life-prolonging, or palliative treatment does not exist or is no longer effective.
- Expected survival longer than 6 weeks from enrollment in the study
- Radiographically or clinically evaluable tumor
- Suitable venous access for the conduct of blood sampling for MLN4924
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- Tumor tissue that, in the opinion of the investigator, can be safely biopsied using a core needle
- Male patients must use an appropriate method of barrier contraception
- Female patients must be postmenopausal, surgically sterilized, or willing to use reliable methods of birth control
- Voluntary written consent
Who cannot join
- Pregnant or lactating
- Major surgery within 14 days prior to the first dose of study treatment
- Serious infection within 14 days prior to the first dose of study treatment
- Receiving antibiotic therapy within 14 days prior to the first dose of study treatment
- Life-threatening illness unrelated to cancer
- Diarrhea that is greater than Grade 1 in severity
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- Systemic antineoplastic therapy within 21 days preceding first dose of study treatment
- Radiotherapy within 21 days preceding first dose of study treatment
- Prior treatment with radiation therapy involving ≥25% of the hematopoietically active bone marrow
- 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.
- Clinically significant central nervous system metastases
- Absolute neutrophil count <1,500/mm3; platelet count <100,000/mm3
- Patients with a prothrombin time or aPTT > 1.5 x the upper limit of the normal range, or with a history of a coagulopathy or bleeding disorder
- Ongoing anti-coagulant therapy that can not be held to permit tumor biopsy
- Calculated creatinine clearance <50 mL/minute
- Bilirubin >1.5 times the upper limit of normal; aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase >2.5 times the upper limit of normal.
- Uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction within the past 6 months
- Abnormalities on 12-lead electrocardiogram including, but not limited to, changes in rhythm and intervals that in the opinion of the investigator are considered to be clinically significant
- Known human immunodeficiency virus positive or hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
- Treatment with any investigational products within 28 days preceding the first dose of study treatment
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Emory University Hospital
Atlanta, Georgia, 30322
Cancer Therapy & Research Center at the UT Health Science Center
San Antonio, Texas, 78229
Institute for Drug Development
San Antonio, Texas, 78229
About this study
Official title: An Open-Label, Dose Escalation, Phase I Study of MLN4924, a Novel Inhibitor of Nedd8-Activating Enzyme, in Adult Patients With Nonhematologic Malignancies
This study is an open-label, multicenter, Phase 1, dose escalation study of MLN4924 in adult patients with nonhematologic malignancies. This study will be the first to administer MLN4924 in humans. The patient population will consist of adults with any form of nonhematologic malignancy for which standard, curative, life prolonging, or palliative treatment does not exist or is no longer effective.
- Conditions
- Advanced Nonhematologic Malignancies
- Being tested
- MLN4924
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MLN4924Drug
IV dose escalation for 5 consecutive days followed by a rest period of 16 days for a 21 day cycle. Treated may continue until disease progression or unacceptable toxicity develops.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | MLN4924 Receives: Drug: MLN4924 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the safety profile, MTD and PK/pharmacodynamics of MLN4924
Measured: Maximum duration of therapy for 12 months
Secondary outcomes (1)
Disease response
Measured: Day 21, every other cycle and end of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2008 (estimated)
- Study startApr 2008
- Primary completionFeb 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Advanced Nonhematologic MalignanciesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Millennium Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00677170
- Sponsor's protocol ID
- C15001
- Status last verified
- Jul 2013
- First submitted
- 9 May 2008
- Last updated
- 16 Jul 2013
- Results posted
- No
Publications
Fu DJ, Wu YJ, Chen C, Zhang C, Su ZQ, Wang T. Pevonedistat targeting NEDDylation activating enzyme for human diseases: Underlying mechanisms, clinical studies, and future directions. Pharmacol Res. 2026 Mar;225:108134. doi: 10.1016/j.phrs.2026.108134. Epub 2026 Feb 11.
PubMed 41687727Faessel 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.
PubMed 31355467Swords RT, Watts J, Erba HP, Altman JK, Maris M, Anwer F, Hua Z, Stein H, Faessel H, Sedarati F, Dezube BJ, Giles FJ, Medeiros BC, DeAngelo DJ. Expanded safety analysis of pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukemia and myelodysplastic syndromes. Blood Cancer J. 2017 Feb 3;7(2):e520. doi: 10.1038/bcj.2017.1. No abstract available.
PubMed 28157218
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Dose Escalation, Phase I Study of MLN4924, a Novel Inhibitor of Nedd8-Activating Enzyme, in Adult Patients With Nonhematologic Malignancies
- ClinicalTrials.gov ID
- NCT00677170
- Acronym / sponsor ID
- C15001
- Conditions
- Advanced Nonhematologic Malignancies
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Millennium Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Apr 2008
- Primary completion
- Feb 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 14 May 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is an open-label, multicenter, Phase 1, dose escalation study of MLN4924 in adult patients with nonhematologic malignancies. This study will be the first to administer MLN4924 in humans. The patient population will consist of adults with any form of nonhematologic malignancy for which standard, curative, life prolonging, or palliative treatment does not exist or is no longer effective.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: MLN4924MLN4924 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female patients 18 years or older
- Eastern Cooperative Oncology Group performance status 0-2
- Patients must have a diagnosis of a nonhematologic malignancy for which standard curative, life-prolonging, or palliative treatment does not exist or is no longer effective.
- Expected survival longer than 6 weeks from enrollment in the study
- Radiographically or clinically evaluable tumor
Key exclusion criteria (20 listed)
- Pregnant or lactating
- Major surgery within 14 days prior to the first dose of study treatment
- Serious infection within 14 days prior to the first dose of study treatment
- Receiving antibiotic therapy within 14 days prior to the first dose of study treatment
- Life-threatening illness unrelated to cancer
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MLN4924IV dose escalation for 5 consecutive days followed by a rest period of 16 days for a 21 day cycle. Treated may continue until disease progression or unacceptable toxicity develops. | Drug | 1 |
Primary outcome
Determine the safety profile, MTD and PK/pharmacodynamics of MLN4924
Time frame: Maximum duration of therapy for 12 months
1 secondary outcome
Disease response
Time frame: Day 21, every other cycle and end of study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2013.
- Derived from this study: PubMed 41687727Fu DJ, Wu YJ, Chen C, Zhang C, Su ZQ, Wang T. Pevonedistat targeting NEDDylation activating enzyme for human diseases: Underlying mechanisms, clinical studies, and future directions. Pharmacol Res. 2026 Mar;225:108134. doi: 10.1016/j.phrs.2026.108134. Epub 2026 Feb 11.
- Derived from this study: PubMed 31355467Faessel 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.
- Derived from this study: PubMed 28157218Swords RT, Watts J, Erba HP, Altman JK, Maris M, Anwer F, Hua Z, Stein H, Faessel H, Sedarati F, Dezube BJ, Giles FJ, Medeiros BC, DeAngelo DJ. Expanded safety analysis of pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukemia and myelodysplastic syndromes. Blood Cancer J. 2017 Feb 3;7(2):e520. doi: 10.1038/bcj.2017.1. No abstract available.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MLN4924 in people with Advanced Nonhematologic Malignancies, run by Millennium Pharmaceuticals, Inc. at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the safety profile, MTD and PK/pharmacodynamics of MLN4924 (time frame: Maximum duration of therapy for 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00677170, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2013; AzTrials last refreshed its copy on 8 Nov 2026.