Table 1 Clinical trials of MLN4924 on AML and MDS, malignant lymphoma, and solid tumors. Information retrieved from ClinicalTrials.gov
Cancer type | Drug name | Combination therapy | Trial name | Phase | Condition or disease | Primary Outcome Measures | Enrollment | Sponsors and Collaborators | Actual Study Start Date | Actual/Estimated Study Completion Date | Recruitment Status | Study identifier |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
AML and MDS | Pevonedistat | Venetoclax, Azacitidine | A Study of Pevonedistat and Venetoclax Combined with Azacitidine to Treat AML in Adults Unable to Receive Intensive Chemotherapy | Phase II | Adult patients with AML who are unable to be treated with intensive chemotherapy. | EFS | 164 participants | Takeda | October 13, 2020 | September 6, 2022 | Active, not recruiting | NCT04266795 |
Pevonedistat | Cytarabine | Pevonedistat and Low Dose Cytarabine in Adult Patients with AML and MDS | Phase I | Adult patients with Relapsed/Refractory AML and Advanced MDS | Safety Profile, MTD, RP2D | 12 participants | Justin Watts, MD; Takeda | May 21, 2018 | June 25, 2021 | Completed | NCT03459859 | |
Pevonedistat | Azacitidine | Study of MLN4924 Plus Azacitidine in Treatment-naive Participants with AML Who Are 60 Years or Older | Phase I | Treatment-Naïve Patients with Acute Myelogenous Leukemia Who Are 60 Years or Older | TEAEs, SAEs | 64 participants | Millennium Pharmaceuticals, Inc. | April 10, 2013 | April 8, 2018 | Completed | NCT01814826 | |
Pevonedistat | Azacitidine, Venetoclax | Pevonedistat, Azacitidine (or Decitabine), and Venetoclax for the Treatment of Patients With AML | Phase I | Patients With AML | RP2D, Toxicity profile | 24 participants | Medical College of Wisconsin | January 13, 2020 | December 1, 2025 | Active, not recruiting | NCT04172844 | |
Pevonedistat | Azacitidine | Treatment of MDS/AML Patients with an Impending Hematological Relapse with AZA or ATA and Pevonedistat | Phase II | MDS/AML Patients with an Impending Hematological Relapse | MRD | 14 participants | University of Leipzig, Millennium Pharmaceuticals, Inc. | January 1, 2021 | January 31, 2023 | Completed | NCT04712942 | |
Pevonedistat | Cytarabine, Idarubicin | Pevonedistat, Cytarabine, and Idarubicin in Treating Patients With AML | Phase I/II | Patients with acute myeloid leukemia | Composite complete response rate; Incidence of adverse events | 53 participants | University of Southern California; NCI | April 18, 2018 | October 13, 2025 | Active, not recruiting | NCT03330821 | |
Pevonedistat | Belinostat | Pevonedistat and Belinostat in Treating Patients with Relapsed or Refractory AML or MDS | Phase I | Patients with Relapsed/Refractory AML or MDS. | RP2D | 30 participants | NCI | June 20, 2019 | July 1, 2024 | Active, not recruiting | NCT03772925 | |
Pevonedistat | Azacitidine, Cytarabine, Fludarabine Phosphate, Methotrexate, Therapeutic Hydrocortisone | Pevonedistat, Azacitidine, Fludarabine Phosphate, and Cytarabine in Treating Patients with Relapsed or Refractory AML or MDS | Phase I | Patients with Relapsed/Refractory AML or MDS. | Dose Limiting Toxicities; Adverse Events | 12 participants | NCI; Children’s Oncology Group | May 1, 2019 | October 5, 2023 | Active, not recruiting | NCT03813147 | |
Pevonedistat | Decitabine | Pevonedistat and Decitabine in Treating Patients with High -Risk AML | Phase I | Patients with high-risk AML. | Adverse Events; DLT; MTD | 30 participants | City of Hope Medical Center; NCI | August 21, 2017 | December 15, 2023 | Active, not recruiting | NCT03009240 | |
Pevonedistat | Azacitidine | Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Participants with Higher-Risk HR MDS, CMML, or Low-Blast AML | Phase III | Patients With HR MDS, CMML, or Low-Blast AML | EFS | 454 participants | Takeda; Takeda Development Center Americas, Inc. | November 28, 2017 | June 30, 2023 | Active, not recruiting | NCT03268954 | |
Pevonedistat | Azacitidine | An Efficacy and Safety Study of Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine in Participants with HR MDS, CMML and Low-Blast AML | Phase II | Participants with HR-MDS or CMML, or low-blast AML | OS | 120 participants | Millennium Pharmaceuticals, Inc. | April 14, 2016 | July 23, 2021 | Completed | NCT02610777 | |
Pevonedistat | Azacitidine | Study to Compare Azacitidine Plus Pevonedistat Versus Azacitidine in Patients with AML Not Eligible for Standard Chemotherapy | Phase III | Patients with newly diagnosed AML not eligible for intensive chemotherapy | OS | 302 participants | PETHEMA Foundation; Millennium Pharmaceuticals, Inc.; Dynamic Science S.L. | September 24, 2019 | June 30, 2023 | Active, not recruiting | NCT04090736 | |
Malignant lymphoma | MLN4924 | None | Study of MLN4924, a Novel Inhibitor of Nedd8 Activating Enzyme, in Adult Patients with Lymphoma or Multiple Myeloma | Phase I | Adult patients with lymphoma or multiple myeloma. | Safety and tolerability | 56 participants | Millennium Pharmaceuticals, Inc. | July 25, 2008 | November 18, 2013 | Completed | NCT00722488 |
Pevonedistat | Ibrutinib | Pevonedistat and Ibrutinib in Treating Participants with Relapsed or Refractory CLL or NHL | Phase I | Participants with chronic lymphocytic leukemia or NHL that has come back or has stopped responding to other treatments. | DLTs, AEs, SAEs | 18 participants | City of Hope Medical Center; National Cancer Institute (NCI) | March 22, 2018 | December 2, 2023 | Active, not recruiting | NCT03479268 | |
Pevonedistat | Irinotecan, Temozolomide | Pevonedistat, Irinotecan, and Temozolomide in Treating Patients with Recurrent or Refractory Solid Tumors or Lymphoma | Phase I | Relapsed/Refractory Solid Tumors or Lymphoma. | MTD, RP2D | 30 participants | Children’s Oncology Group; National Cancer Institute (NCI) | November 13, 2017 | September 30, 2023 | Active, not recruiting | NCT03323034 | |
Pevonedistat | Vincristine, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, Methotrexate, Hydrocortisone | Pevonedistat with VXLD Chemotherapy for Adolescent/Young Adults with Relapsed/Refractory ALL or Lymphoblastic NHL | Phase I | Adolescent/Young Adults with Relapsed/Refractory ALL or Lymphoblastic NHL. | Toxicity, MTD | 6 participants | Julio Barredo, MD; Takeda | March 25, 2019 | October 12, 2022 | Completed | NCT03349281 | |
MLN4924 | Azacitidine | MLN4924Â for the Treatment of AML, MDS, and ALL | Phase I | AML, MDS, and ALL | Adverse events, serious adverse events, assessments of clinical laboratory values, and vital sign measurements | 72 participants | Millennium Pharmaceuticals, Inc. | June 1, 2009 | December 5, 2013 | Completed | NCT00911066 | |
Solid Tumors | MLN4924 | Paclitaxel, Gemcitabine, Docetaxel, Carboplatin | Dose Escalation, Multi-arm Study of MLN4924 Plus Docetaxel, Gemcitabine, or Combination of Carboplatin and Paclitaxel in Participants with Solid Tumors | Phase I | Solid tumors. | TEAEs, SAEs | 64 participants | Millennium Pharmaceuticals, Inc. | June 10, 2013 | May 21, 2018 | Completed | NCT01862328 |
MLN4924 | Fluconazole, Itraconazole, Docetaxel, Carboplatin, Paclitaxel | Effects of Fluconazole and Itraconazole CYP3A-Mediated Inhibition on the Pharmacokinetics, Safety, and Tolerability of MLN4924 in Participants with Advanced Solid Tumors | Phase I | Solid tumors. | Area Under the Plasma Concentration-time Curve | 51 participants | Millennium Pharmaceuticals, Inc. | April 1, 2014 | June 5, 2017 | Completed | NCT02122770 | |
Pevonedistat | Irinotecan, Temozolomide | Pevonedistat, Irinotecan, and Temozolomide in Treating Patients with Recurrent or Refractory Solid Tumors or Lymphoma | Phase I | Relapsed/Refractory Solid Tumors or Lymphoma | MTD, RP2D | 30 participants | Children’s Oncology Group, NCI | November 13, 2017 | September 30, 2023 | Active, not recruiting | NCT03323034 | |
Pevonedistat | Rifampin, Docetaxel, Carboplatin, Paclitaxel | A Study to Evaluate the Effects of Rifampin on Pharmacokinetics (PK) of Pevonedistat in Participants with Advanced Solid Tumors | Phase I | Advanced Solid Tumors | Cmax, Area Under the Plasma Concentration-time Curve | 20 participants | Millennium Pharmaceuticals, Inc. | August 13, 2018 | February 28, 2021 | Completed | NCT03486314 | |
Pevonedistat | Azacitidine, Docetaxel, Paclitaxel, Carboplatin | A Study of Pevonedistat in People with Blood Cancers or Solid Tumors with Kidney or Liver Problems | Phase I | Blood cancers or solid tumors | Area Under the Plasma Concentration-time Curve | 17 participants | Takeda | July 10, 2019 | April 19, 2022 | Completed | NCT03814005 | |
Pevonedistat | Docetaxel, Carboplatin, Paclitaxel | A Study to Evaluate the Effects of Pevonedistat on the Corrected QT (QTc) Interval in Participants with Advanced Solid Tumors | Phase I | Advanced Solid Tumors | QTcF | 68 participants | Millennium Pharmaceuticals, Inc. | November 6, 2017 | March 28, 2023 | Completed | NCT03330106 | |
Pevonedistat | Carboplatin, Paclitaxel | Testing the Combination of MLN4924 (Pevonedistat), Carboplatin, and Paclitaxel in Patients with Advanced NSCLC Who Have Previously Been Treated with Immunotherapy | Phase II | Advanced NSCLC Who Have Previously Been Treated with Immunotherapy | ORR | 24 participants | NCI | September 3, 2019 | March 9, 2024 | Active, not recruiting | NCT03965689 | |
Pevonedistat | Carboplatin, Paclitaxel | Testing the Combination of Pevonedistat with Chemotherapy for Bile Duct Cancer of the Liver | Phase II | Bile Duct Cancer of the Liver | Objective response rate | 52 participants | NCI | January 31, 2020 | October 1, 2023 | Active, not recruiting | NCT04175912 |