Acute Myelogenous LeukemiaPhase 1NCT00911066
MLN4924 for the Treatment of Acute Myelogenous Leukemia, Myelodysplastic Syndrome, and Acute Lymphoblastic Leukemia
A Phase 1 study testing MLN4924 and Azacitidine in people with Acute Myelogenous Leukemia and Acute Lymphoblastic Leukemia, run by Millennium Pharmaceuticals, Inc. at 6 sites in United States.
Trial summary
An open-label, multicenter, phase 1, dose escalation study of MLN4924 in adult patients with acute myelogenous leukemia (AML), high-grade myelodysplastic syndrome (MDS). The patient population will consist of adults previously diagnosed with AML including high-grade MDS for which standard curative, life-prolonging… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myelogenous Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome
- What is being tested?
- MLN4924 and Azacitidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 6 sitesUnited States
- Study dates
- Jun 2009to Oct 2013
- 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
- Age greater than or equal to 18 years
- Have the following diagnosis:
- AML or ALL (for the dose escalation phase only)including leukemia secondary to prior chemotherapy or resulting from an antecedent hematologic disorder, who have failed to achieve complete response (CR) or who have relapsed after prior therapy and are not candidates for potentially curative treatment.
- Acute Promyelocytic Leukemia (APL) patients are not eligible
- AML or ALL patients who are over age 60 and have not received prior therapy are also eligible if they are not candidates for standard induction chemotherapy
- High-grade MDS, defined as > 10% blasts on bone marrow examination
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- Low-grade MDS, defined as < 10% blasts on bone marrow examination (Schedule B expansion cohort only)
- Patients who are willing to refrain from donating blood for at least 90 days after their final dose of MLN4924 and (for male patients) willing to refrain from donating semen for at least 4 months after their final dose of MLN4924
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- Female patients who are postmenopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse
- Male patients who agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse
- Voluntary written consent
- Suitable venous access
- Adequate clinical laboratory values during the screening period as specified in the protocol
- Patients who are on hydroxyurea may be included in the study and may continue on hydroxyurea while participating in this study.
Who cannot join
- Female patients who are lactating or have a positive serum pregnancy test during the screening period
- Any serious medical or psychiatric illness
- Treatment with any investigational products
- Systemic antineoplastic therapy or radiotherapy within 14 days before the first dose of study drug, except for hydroxyurea
- Major surgery within 14 days before the first dose of study drug
- Life-threatening illness unrelated to cancer
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- Clinically uncontrolled central nervous system (CNS) involvement
- Known human immunodeficiency virus (HIV) positive
- Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection
- Evidence of uncontrolled cardiovascular conditions as specified in the protocol
- Diarrhea > Grade 1, based on the NCI CTCAE categorization
- Systemic treatment with prohibited medications
- Ongoing anticoagulant therapy (eg, aspirin, Coumadin, heparin) that cannot be held to permit bone marrow sampling
- Use of acetaminophen, acetaminophen-containing products, and statins are not permitted on the day before dosing, day of dosing, and day after dosing with MLN4924
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
Johns Hopkins Kimmel Cancer Center
Baltimore, Maryland, 21287
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Robert H. Lurie Comprehensive Cancer Center Northwestern University
Chicago, Illinois, 60657
Institute for Drug Development
San Antonio, Texas, 78229
Stanford University Medical Center
Stanford, California, 94305
About this study
Official title: An Open-Label, Dose Escalation, Phase 1 Study of MLN4924, a Novel Inhibitor of Nedd8-Activating Enzyme, in Adult Patients With Acute Myelogenous Leukemia,Myelodysplastic Syndrome, and Acute Lymphoblastic Leukemia
An open-label, multicenter, phase 1, dose escalation study of MLN4924 in adult patients with acute myelogenous leukemia (AML), high-grade myelodysplastic syndrome (MDS). The patient population will consist of adults previously diagnosed with AML including high-grade MDS for which standard curative, life-prolonging treatment does not exist or is no longer effective.
- Being tested
- MLN4924, Azacitidine
- Medical subject headings
- Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MLN4924Drug
MLN4924 intravenous (IV) on a 21-day cycle on one of the following schedules:
- Days 1, 3, and 5, followed by a rest period of 16 days (Schedule A)
- Days 1, 4, 8, and 11, followed by a rest period of 10 days (Schedule B)
- Continuous weekly dosing on Days 1, 8, and 15 (Schedule C)
- Days 1, 4, 11, 15 for Cycle 1 only; Days 1, 4, 8, 11 for all subsequent cycles (Schedule D)
- Dosing on Days 1, 3, and 5 in patients with high-grade MDS or AML (Schedule E)
AzacitidineDrug
Azacitidine will be administered (IV or subcutaneous (SC)) on Days 8 to 12 and Days 15 and 16 in Cycle 1, and on Days 1 to 5 and Days 8 to 9 (Schedule D)
| Study group | Role | What they receive |
|---|---|---|
| MLN4924 | Experimental | Not described Receives: Drug: MLN4924 |
| Azacitidine | Experimental | Not described Receives: Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events, serious adverse events, assessments of clinical laboratory values, and vital sign measurements
Measured: 12 months
Secondary outcomes (4)
Pharmacokinetic parameters
Measured: 12 months
Pharmacodynamic effects
Measured: 12 months
Assess disease response
Measured: 12 months
Heart corrected QT intervals
Measured: During screening and during Cycle 1, Days 1 and 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2009 (estimated)
- Study startJun 2009
- Primary completionAug 2013
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Myelogenous LeukemiaStudies 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
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Millennium Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Millennium Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00911066
- Sponsor's protocol ID
- C15003
- Status last verified
- Dec 2013
- First submitted
- 28 May 2009
- Last updated
- 5 Dec 2013
- Results posted
- No
- Data monitoring committee
- No
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.
PubMed 31355467Swords RT, Erba HP, DeAngelo DJ, Bixby DL, Altman JK, Maris M, Hua Z, Blakemore SJ, Faessel H, Sedarati F, Dezube BJ, Giles FJ, Medeiros BC. Pevonedistat (MLN4924), a First-in-Class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a phase 1 study. Br J Haematol. 2015 May;169(4):534-43. doi: 10.1111/bjh.13323. Epub 2015 Mar 2.
PubMed 25733005
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Dose Escalation, Phase 1 Study of MLN4924, a Novel Inhibitor of Nedd8-Activating Enzyme, in Adult Patients With Acute Myelogenous Leukemia,Myelodysplastic Syndrome, and Acute Lymphoblastic Leukemia
- ClinicalTrials.gov ID
- NCT00911066
- Acronym / sponsor ID
- C15003
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Millennium Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Jun 2009
- Primary completion
- Aug 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 1 Jun 2009 (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.
An open-label, multicenter, phase 1, dose escalation study of MLN4924 in adult patients with acute myelogenous leukemia (AML), high-grade myelodysplastic syndrome (MDS). The patient population will consist of adults previously diagnosed with AML including high-grade MDS for which standard curative, life-prolonging 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
- 2
| Arm | Type | Receives |
|---|---|---|
| MLN4924 | Experimental | Drug: MLN4924 |
| Azacitidine | Experimental | Drug: Azacitidine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Age greater than or equal to 18 years
- Have the following diagnosis:
- Patients who are willing to refrain from donating blood for at least 90 days after their final dose of MLN4924 and (for male patients) willing to refrain from donating semen for at least 4 months after their final dose of MLN4924
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- Female patients who are postmenopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse
Key exclusion criteria (14 listed)
- Female patients who are lactating or have a positive serum pregnancy test during the screening period
- Any serious medical or psychiatric illness
- Treatment with any investigational products
- Systemic antineoplastic therapy or radiotherapy within 14 days before the first dose of study drug, except for hydroxyurea
- Major surgery within 14 days before the first dose of study drug
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 |
|---|---|---|
| MLN4924MLN4924 intravenous (IV) on a 21-day cycle on one of the following schedules: * Days 1, 3, and 5, followed by a rest period of 16 days (Schedule A) * Days 1, 4, 8, and 11, followed by a rest period of 10 days (Schedule B) * Continuous weekly dosing on Days 1, 8, and 15 (Schedule C) * Days 1, 4, 11, 15 for Cycle 1 only; Days 1, 4, 8, 11 for all subsequent cycles (Schedule D) * Dosing on Days 1, 3, and 5 in patients with high-grade MDS or AML (Schedule E) | Drug | MLN4924 |
| AzacitidineAzacitidine will be administered (IV or subcutaneous (SC)) on Days 8 to 12 and Days 15 and 16 in Cycle 1, and on Days 1 to 5 and Days 8 to 9 (Schedule D) | Drug | Azacitidine |
Primary outcome
Adverse events, serious adverse events, assessments of clinical laboratory values, and vital sign measurements
Time frame: 12 months
4 secondary outcomes
Pharmacokinetic parameters
Time frame: 12 months
Pharmacodynamic effects
Time frame: 12 months
Assess disease response
Time frame: 12 months
Heart corrected QT intervals
Time frame: During screening and during Cycle 1, Days 1 and 15
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 5 Dec 2013.
- 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 25733005Swords RT, Erba HP, DeAngelo DJ, Bixby DL, Altman JK, Maris M, Hua Z, Blakemore SJ, Faessel H, Sedarati F, Dezube BJ, Giles FJ, Medeiros BC. Pevonedistat (MLN4924), a First-in-Class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a phase 1 study. Br J Haematol. 2015 May;169(4):534-43. doi: 10.1111/bjh.13323. Epub 2015 Mar 2.
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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.
Medical Monitor study director
Millennium Pharmaceuticals, Inc.
6 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 and Azacitidine in people with Acute Myelogenous Leukemia and Acute Lymphoblastic Leukemia, run by Millennium Pharmaceuticals, Inc. at 6 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 15 inclusion and 14 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 5 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 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?
Adverse events, serious adverse events, assessments of clinical laboratory values, and vital sign measurements (time frame: 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 NCT00911066, which also lists 2 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 5 Dec 2013.