Trial · NCT03772925
Pevonedistat and Belinostat in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
NCT03772925, Phase 1, Terminated, National Cancer Institute (NCI); results first posted 2026-03-03
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Pevonedistat and Belinostat in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome. Trials, record NCT03772925. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT03772925
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Pevonedistat and Belinostat in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
- NCT number
- NCT03772925
- Status
- Terminated
- Phases
- Phase 1
- Enrollment
- 18 participants, actual
- Lead sponsor
- National Cancer Institute (NCI)
- Conditions
- Recurrent Acute Myeloid Leukemia, Recurrent Myelodysplastic Syndrome, Refractory Acute Myeloid Leukemia, Refractory Myelodysplastic Syndrome
- Interventions
- Belinostat, Pevonedistat
- First posted
- 2018-12-12
- Last updated
- 2026-03-03
- Results first posted
- 2026-03-03
- Limitations and caveats
- Takeda stopped producing Pevonedistat
Source ClinicalTrials.gov
Registered outcomes20
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Recommended Phase 2 Dose (RP2D) for the Combination of MLN4924 (Pevonedistat) and Belinostat | Up to the end of cycle 1, 21 days. | Determined by the number of patients with treatment dosing level toxicities (DLT's). DLT's will be defined in cycle 1 as pre-specified adverse events that are considered by the investigator to be related to therapy with MLN4924 (pevonedistat) and/or belinostat. |
| Secondary | Incidence of Adverse Events (AEs) | Adverse Events (AE's) were collected starting Cycle 1 Day 1 through 30 days following treatment up to 1 year, 6 months. | Number of graded Adverse Events (AEs) reported using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. |
| Secondary | Treatment Response | From day 1 until final response measured, up to 188 days. | The percentage of participants that experience a decrease in tumor size (partial response), or disappearance of tumor (complete response), classified according to International Working Group (IWG) and European Leukemia Net (ELN) criteria for response assessment in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). |
| Secondary | Duration of Stable and Complete Response | From documentation of tumor response to disease progression or death assessed up to 188 days. | Number of days patients remained in stable or complete response. |
| Secondary | Time to Response | From Day 1 of protocol treatment to the time of documentation of tumor response, assessed up to 188 days. | Number of days from day 1 of therapy to best response. |
| Secondary | Change in MLN4924 Belinostat Plasma Concentrations | Baseline up to cycle 1 day 1 | Pharmacokinetic parameters in MLN4924 belinostat will be calculated using standard non-compartmental methods and summarized as geometric mean and geometric coefficient of variation. |
| Secondary | Change in MLN4924 Pevonedistat Plasma Concentrations | Baseline up to cycle 1 day 1 | Pharmacokinetic (PK) parameters in MLN4924 pevonedistat will be calculated using standard non-compartmental methods and summarized as geometric mean and geometric coefficient of variation. |
| Secondary | Change in MLN4924 Belinostat Glucuronide Plasma Concentrations | Baseline up to cycle 1 day 1 | Pharmacokinetic parameters in MLN4924 belinostat glucuronide will be calculated using standard non-compartmental methods and summarized as geometric mean and geometric coefficient of variation. |
| Other | Determine What Relationship, if Any, Exists Between Such Responses and TP53/FLT3 Mutational Status. | Screening | TP53 and FLT3 mutational status by NGS compared to best clinical response classified according to International Working Group (IWG) and European Leukemia Net (ELN) criteria for response assessment in AML and MDS using a specific hematologic and blast count thresholds to define outcomes like Complete Remission (CR) or Hematologic Improvement (HI), focusing on blood counts (Hb, ANC, Platelets) and bone marrow (BM) blasts, with recent updates (IWG 2023/2024) emphasizing clearer definitions, limited recovery categories (CRi, CRL), and incorporating transfusion dependency/independence for better clinical relevance. Scoring isn't a single number but categorizing responses (CR, CRi, HI, Failure). |
| Other | Change in Candidate Biomarker Levels in Bone Marrow and/or Blood Samples gH2A.X | Baseline up to 24 hours post-treatment with the first doses of study drugs | Paired t-tests will be used to determine if there is a significant change in each of the candidate biomarker between the pre- and 24-hour post-treatment assessments, in bone marrow samples and/or blood samples. |
1 to 10 of 20Source ClinicalTrials.gov
See all 20 registered outcomesOutcomes20
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Recommended Phase 2 Dose (RP2D) for the Combination of MLN4924 (Pevonedistat) and Belinostat | Up to the end of cycle 1, 21 days. | 2 patients in dose level 5 did not complete treatment. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Incidence of Adverse Events (AEs) | Adverse Events (AE's) were collected starting Cycle 1 Day 1 through 30 days following treatment up to 1 year, 6 months. | Adverse Events Reported | NUMBER | |
| SECONDARY | Treatment Response | From day 1 until final response measured, up to 188 days. | 4 participants not assessed. (1 patient receiving dose level 1, 3 receiving dose level 4) These patients stopped treatment too early to assess response. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Duration of Stable and Complete Response | From documentation of tumor response to disease progression or death assessed up to 188 days. | 5 participants that had either complete response or stable disease were measured. | Days | MEAN |
| SECONDARY | Time to Response | From Day 1 of protocol treatment to the time of documentation of tumor response, assessed up to 188 days. | 4 participants not assessed (1 receiving dose level 1, 3 receiving dose level 4 due to stopping treatment too early to measure response.) | Days | MEAN |
| SECONDARY | Change in MLN4924 Belinostat Plasma Concentrations | Baseline up to cycle 1 day 1 | 2 participants receiving dose level 5 had insufficient blast% to analyze the sample, per the protocol | ng/ml | MEAN |
| SECONDARY | Change in MLN4924 Pevonedistat Plasma Concentrations | Baseline up to cycle 1 day 1 | Change in MLN4924 pevonedistat plasma concentrations specimens were drawn, but were not analyzed at dose level #5 because the PK studies were done by the pharmaceutical sponsor (Takeda). As Takeda had decided to terminate the trial, they elected not to complete the pevonedistat PK analysis at dose level #5. The samples will not be analyzed in the future. | ng/ml | MEAN |
| SECONDARY | Change in MLN4924 Belinostat Glucuronide Plasma Concentrations | Baseline up to cycle 1 day 1 | ng/ml | MEAN | |
| OTHER_PRE_SPECIFIED | Determine What Relationship, if Any, Exists Between Such Responses and TP53/FLT3 Mutational Status. | Screening | |||
| OTHER_PRE_SPECIFIED | Change in Candidate Biomarker Levels in Bone Marrow and/or Blood Samples gH2A.X | Baseline up to 24 hours post-treatment with the first doses of study drugs |
1 to 10 of 20Source ClinicalTrials.gov
See all 20 outcomesResults by group72
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Recommended Phase 2 Dose (RP2D) for the Combination of MLN4924 (Pevonedistat) and Belinostat | Treatment (Belinostat, Pevonedistat) Dose Level 1 | 0 | Participants | ||
| Recommended Phase 2 Dose (RP2D) for the Combination of MLN4924 (Pevonedistat) and Belinostat | Treatment (Belinostat, Pevonedistat) Dose Level 2 | 0 | Participants | ||
| Recommended Phase 2 Dose (RP2D) for the Combination of MLN4924 (Pevonedistat) and Belinostat | Treatment (Belinostat, Pevonedistat) Dose Level 3 | 0 | Participants | ||
| Recommended Phase 2 Dose (RP2D) for the Combination of MLN4924 (Pevonedistat) and Belinostat | Treatment (Belinostat, Pevonedistat) Dose Level 4 | 0 | Participants | ||
| Recommended Phase 2 Dose (RP2D) for the Combination of MLN4924 (Pevonedistat) and Belinostat | Treatment (Belinostat, Pevonedistat) Dose Level 5 | 0 | Participants | ||
| Incidence of Adverse Events (AEs) | Treatment (Belinostat, Pevonedistat) Dose Level 1 | Number of Grade 1 AE's | 57 | Adverse Events Reported | |
| Incidence of Adverse Events (AEs) | Treatment (Belinostat, Pevonedistat) Dose Level 2 | Number of Grade 1 AE's | 34 | Adverse Events Reported | |
| Incidence of Adverse Events (AEs) | Treatment (Belinostat, Pevonedistat) Dose Level 3 | Number of Grade 1 AE's | 75 | Adverse Events Reported | |
| Incidence of Adverse Events (AEs) | Treatment (Belinostat, Pevonedistat) Dose Level 4 | Number of Grade 1 AE's | 49 | Adverse Events Reported | |
| Incidence of Adverse Events (AEs) | Treatment (Belinostat, Pevonedistat) Dose Level 5 | Number of Grade 1 AE's | 127 | Adverse Events Reported |
1 to 10 of 72Source ClinicalTrials.gov
See all 72 results by groupParticipant flow15
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Treatment (Belinostat, Pevonedistat) Dose Level 1 | 3 | |
| Overall Study | STARTED | Treatment (Belinostat, Pevonedistat) Dose Level 2 | 3 | |
| Overall Study | STARTED | Treatment (Belinostat, Pevonedistat) Dose Level 3 | 3 | |
| Overall Study | STARTED | Treatment (Belinostat, Pevonedistat) Dose Level 4 | 4 | |
| Overall Study | STARTED | Treatment (Belinostat, Pevonedistat) Dose Level 5 | 5 | |
| Overall Study | COMPLETED | Treatment (Belinostat, Pevonedistat) Dose Level 1 | 3 | |
| Overall Study | COMPLETED | Treatment (Belinostat, Pevonedistat) Dose Level 2 | 3 | |
| Overall Study | COMPLETED | Treatment (Belinostat, Pevonedistat) Dose Level 3 | 3 | |
| Overall Study | COMPLETED | Treatment (Belinostat, Pevonedistat) Dose Level 4 | 4 | |
| Overall Study | COMPLETED | Treatment (Belinostat, Pevonedistat) Dose Level 5 | 3 |
1 to 10 of 15Source ClinicalTrials.gov
See all 15 participant flowAdverse events620
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Anemia | Blood and lymphatic system disorders | Treatment (Belinostat, Pevonedistat) Dose Level 1 | 1 | 3 | 2 |
| other | Anemia | Blood and lymphatic system disorders | Treatment (Belinostat, Pevonedistat) Dose Level 2 | 3 | 3 | 7 |
| other | Anemia | Blood and lymphatic system disorders | Treatment (Belinostat, Pevonedistat) Dose Level 3 | 3 | 3 | 23 |
| other | Anemia | Blood and lymphatic system disorders | Treatment (Belinostat, Pevonedistat) Dose Level 4 | 2 | 4 | 5 |
| other | Anemia | Blood and lymphatic system disorders | Treatment (Belinostat, Pevonedistat) Dose Level 5 | 0 | 5 | 0 |
| other | Febrile neutropenia | Blood and lymphatic system disorders | Treatment (Belinostat, Pevonedistat) Dose Level 1 | 1 | 3 | 3 |
| other | Febrile neutropenia | Blood and lymphatic system disorders | Treatment (Belinostat, Pevonedistat) Dose Level 2 | 0 | 3 | 0 |
| other | Febrile neutropenia | Blood and lymphatic system disorders | Treatment (Belinostat, Pevonedistat) Dose Level 3 | 1 | 3 | 1 |
| other | Febrile neutropenia | Blood and lymphatic system disorders | Treatment (Belinostat, Pevonedistat) Dose Level 4 | 0 | 4 | 0 |
| other | Febrile neutropenia | Blood and lymphatic system disorders | Treatment (Belinostat, Pevonedistat) Dose Level 5 | 1 | 5 | 2 |
1 to 10 of 620Source ClinicalTrials.gov
See all 620 adverse eventsAdverse event totals15
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Treatment (Belinostat, Pevonedistat) Dose Level 1 | 1 | 3 |
| Total, all-cause mortality | Treatment (Belinostat, Pevonedistat) Dose Level 2 | 0 | 3 |
| Total, all-cause mortality | Treatment (Belinostat, Pevonedistat) Dose Level 3 | 1 | 3 |
| Total, all-cause mortality | Treatment (Belinostat, Pevonedistat) Dose Level 4 | 0 | 4 |
| Total, all-cause mortality | Treatment (Belinostat, Pevonedistat) Dose Level 5 | 0 | 5 |
| Total, other adverse events | Treatment (Belinostat, Pevonedistat) Dose Level 1 | 3 | 3 |
| Total, other adverse events | Treatment (Belinostat, Pevonedistat) Dose Level 2 | 3 | 3 |
| Total, other adverse events | Treatment (Belinostat, Pevonedistat) Dose Level 3 | 3 | 3 |
| Total, other adverse events | Treatment (Belinostat, Pevonedistat) Dose Level 4 | 4 | 4 |
| Total, other adverse events | Treatment (Belinostat, Pevonedistat) Dose Level 5 | 5 | 5 |
1 to 10 of 15Source ClinicalTrials.gov
See all 15 adverse event totalsPapers1
The papers the trial lists on ClinicalTrials.gov.
| PMID | Listed as |
|---|---|
| 39821392 | DERIVED |
Source PubMed
Grants1
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
| Project | Title | Principal investigators | Organization | Funder | Fiscal years |
|---|---|---|---|---|---|
| UM1CA186644 | North American Star Consortium | BEDARD, PHILIPPE; COURTNEY, KEVIN D; GRANT, STEVEN; LANCET, JEFFREY; MAHALINGAM, DEVALINGAM; SIU, LILLIAN L | UNIVERSITY HEALTH NETWORK | NATIONAL CANCER INSTITUTE | 2014 to 2025 |
Source NIH RePORTER
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT03772925
GET https://conductscience.org/api/trials/v1/NCT03772925/results?page=2