Clinical Trials Logo

Clinical Trial Summary

This phase I trial studies the side effects and how well pevonedistat, azacitidine, fludarabine phosphate, and cytarabine work in treating patients with acute myeloid leukemia or myelodysplastic syndrome that has come back (relapsed) or has not responded to treatment (refractory). Pevonedistat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as azacitidine, fludarabine phosphate, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) and pevonedistat may work better in treating patients with acute myeloid leukemia or myelodysplastic syndrome.


Clinical Trial Description

PRIMARY OBJECTIVES: I. To evaluate the tolerability and feasibility of MLN4924 (pevonedistat) added to the 3-drug backbone of azacitidine (aza), fludarabine phosphate (fludarabine), and cytarabine re-induction for pediatric patients with recurrent/refractory acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). II. To define and describe the toxicities of MLN4924 (pevonedistat) when given in combination with azacitidine, fludarabine, and cytarabine to pediatric patients with relapsed/refractory AML and MDS. III. To characterize the pharmacokinetics of MLN4924 (pevonedistat) in children with recurrent or refractory AML and MDS. SECONDARY OBJECTIVE: I. To describe the antitumor activity of MLN4924 (pevonedistat) in combination with azacitidine, fludarabine, and cytarabine within the confines of a feasibility study. EXPLORATORY OBJECTIVES: I. To describe the effect of MLN4924 (pevonedistat) administered on this schedule on messenger ribonucleic acid (mRNA) transcript levels of genes known to be induced by MLN4924 (pevonedistat) mediated NEDD8 activating enzyme (NAE) inhibition. II. To describe the effect of MLN4924 (pevonedistat) on NEDDylation of proteins in the NEDD8 pathway that are likely to be affected by NAE inhibition with MLN4924 (pevonedistat). OUTLINE: Patients receive cytarabine intrathecally on day 0 at least 24 hours prior to the start of each cycle. Patients then receive azacitidine intravenously (IV) over 15 minutes once daily (QD) on days 1-5, pevonedistat IV over 60 minutes on days 1, 3, and 5, and fludarabine phosphate IV over 30 minutes QD and cytarabine IV over 1-3 hours QD on days 6-10. Patients with central nervous system (CNS)2 or CNS3 receive cytarabine intrathecally or methotrexate intrathecally, hydrocortisone intrathecally, and cytarabine intrathecally on days 8 and 11-34. Cycles continue for 35 days in the absence of disease progression or unacceptable toxicity. Patients with stable or greater with non-hematologic toxicities probably or definitely related to pevonedistat may receive an additional cycle of treatment. After completion of study treatment, patients are followed up for 30 days. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03813147
Study type Interventional
Source National Cancer Institute (NCI)
Contact
Status Completed
Phase Phase 1
Start date May 17, 2019
Completion date December 31, 2023

See also
  Status Clinical Trial Phase
Active, not recruiting NCT02890329 - Ipilimumab and Decitabine in Treating Patients With Relapsed or Refractory Myelodysplastic Syndrome or Acute Myeloid Leukemia Phase 1
Active, not recruiting NCT04975919 - Venetoclax in Combination With Decitabine and Cedazuridine for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia Phase 2
Terminated NCT02882321 - Oxidative Phosphorylation Inhibitor IACS-010759 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Phase 1
Recruiting NCT03214562 - Venetoclax With Combination Chemotherapy in Treating Patients With Newly Diagnosed or Relapsed or Refractory Acute Myeloid Leukemia Phase 1/Phase 2
Active, not recruiting NCT03289910 - Topotecan Hydrochloride and Carboplatin With or Without Veliparib in Treating Advanced Myeloproliferative Disorders and Acute Myeloid Leukemia or Chronic Myelomonocytic Leukemia Phase 2
Completed NCT02756572 - Early Allogeneic Hematopoietic Cell Transplantation in Treating Patients With Relapsed or Refractory High-Grade Myeloid Neoplasms Phase 2
Completed NCT02509546 - 8-Chloroadenosine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Phase 1/Phase 2
Recruiting NCT03683433 - Enasidenib and Azacitidine in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia and IDH2 Gene Mutation Phase 2
Completed NCT02551718 - High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia N/A
Completed NCT02070458 - Ixazomib, Mitoxantrone Hydrochloride, Etoposide, and Intermediate-Dose Cytarabine in Relapsed or Refractory Acute Myeloid Leukemia Phase 1
Terminated NCT03557970 - JNJ-40346527 in Treating Participants With Relapsed or Refractory Acute Myeloid Leukemia Phase 2
Recruiting NCT03661307 - Quizartinib, Decitabine, and Venetoclax in Treating Participants With Untreated or Relapsed Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome Phase 1/Phase 2
Recruiting NCT03629171 - Liposome-encapsulated Daunorubicin-Cytarabine and Venetoclax in Treating Participants With Relapsed, Refractory or Untreated Acute Myeloid Leukemia Phase 2
Recruiting NCT05396859 - Entrectinib in Combination With ASTX727 for the Treatment of Relapsed/Refractory TP53 Mutated Acute Myeloid Leukemia Phase 1
Terminated NCT03067571 - Daratumumab in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome Phase 2
Completed NCT04146038 - Salsalate, Venetoclax, and Decitabine or Azacitidine for the Treatment of Acute Myeloid Leukemia or Advanced Myelodysplasia/Myeloproliferative Disease Phase 2
Suspended NCT03128034 - 211^At-BC8-B10 Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome, or Mixed-Phenotype Acute Leukemia Phase 1/Phase 2
Active, not recruiting NCT04207190 - Talazoparib and Gemtuzumab Ozogamicin for the Treatment of CD33 Positive Relapsed or Refractory Acute Myeloid Leukemia Phase 1
Recruiting NCT04047641 - Cladribine, Idarubicin, Cytarabine, and Quizartinib in Treating Patients With Newly Diagnosed, Relapsed, or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome Phase 1/Phase 2
Withdrawn NCT04493099 - Alvocidib in Combination With Decitabine and Venetoclax in Patients With Relapsed or Refractory AML or as Frontline Therapy in Unfit Patients With AML Phase 1/Phase 2