A Study of Pevonedistat Combined With Decitabine and Cedazuridine in Adults With Higher-risk Myelodysplastic Syndromes

NCT04985656 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: Pevonedistat-2003
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The main aim of the study is to see if signs and symptoms of myelodysplastic syndromes disappear when treated with pevonedistat combined with decitabine and cedazuridine. Participants will receive an infusion of pevonedistat 3 times during a 28-day cycle. They will also take decitabine and cedazuridine tablets once a day for the first 5 days of the same cycle. A minimum of 6 28-day cycles is recommended, but participants can stop treatment at any time. A bone marrow biopsy, bone marrow aspirates, and blood samples will be collected during the study. Participants will attend a follow-up visit 30 days after their last dose of pevonedistat. Once treatment has ended, participants will be followed up with either monthly clinic visits or will be contacted every 3 months.

Conditions

Myelodysplastic Syndromes (MDS)

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Complete Remission (CR) Rate

  CR Rate is defined as percentage of participants with HR MDS who achieve CR. CR for HR MDS as per the Modified IWG Response Criteria is defined as ≤5% myeloblasts with normal maturation of all cell lines in the bone marrow, and ≥11 grams per deciliter (g/dL) Hemoglobin (Hb), ≥100\*10\^9 per liter (/L) platelets (pl), ≥1.0\*10\^9/L neutrophils and 0% blasts in peripheral blood.

  Up to 30 months

Secondary Outcomes (9)

• Duration of Complete Remission (DOR)

  Up to 30 months

• Overall Response Rate (ORR)

  Up to 30 months

• Time to First CR or PR or Hematologic Improvement (HI)

  Up to 30 months

• Percentage of Participants with Hematologic Improvement

  Up to 30 months

• Percentage of Participants with Red Blood Cell (RBC) Transfusion Independence, Platelet Transfusion Independence, and RBC and Platelet Transfusion Independence

  Up to 30 months

Study Arms (1)

Pevonedistat 20 mg/m^2 + Decitabine 35 mg + Cedazuridine 100 mg

EXPERIMENTAL

Pevonedistat 20 mg/m\^2, 60-minute intravenous (IV) infusion, once daily, on Days 1, 3, and 5 in each 28-day cycle in combination with decitabine 35 mg and cedazuridine 100 mg tablets, orally, once daily on Days 1 through 5 in each 28-day cycle up to 30 months.

Drug: Pevonedistat; Drug: Decitabine; Drug: Cedazuridine

Interventions

Pevonedistat DRUG

Pevonedistat IV infusion

Pevonedistat 20 mg/m^2 + Decitabine 35 mg + Cedazuridine 100 mg

Decitabine DRUG

Decitabine tablets

Pevonedistat 20 mg/m^2 + Decitabine 35 mg + Cedazuridine 100 mg

Cedazuridine DRUG

Cedazuridine tablets

Pevonedistat 20 mg/m^2 + Decitabine 35 mg + Cedazuridine 100 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented morphologically confirmed diagnosis of HR MDS according to the 2016 World Health Organisation (WHO) classification.
• All participants must also have one of the following Prognostic Risk Categories based on the Revised International Prognostic Staging System (IPSS-R): Very high \>6 points, high (4.5 to 6 points), or intermediate \>3 to 4.5 points. Participants in the intermediate category must have \>5% bone marrow myeloblasts.
• Have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of ≤2.
• Able to undergo the study-required bone marrow sample collection procedures.
• Suitable venous access for the study-required blood sampling (i.e., including pharmacokinetic (PK) sampling).
• Known Human Immunodeficiency Virus (HIV)-positive participants who meet the following criteria will be considered eligible:
• Cluster of differentiation 4 (CD4) count \>350 cells per cubic millimeter (cells/mm\^3).
• Undetectable viral load.
• Maintained on modern therapeutic regimens.
• No history of Acquired Immune Deficiency Syndrome (AIDS)-defining opportunistic infections.

You may not qualify if:

• Histologically or cytologically documented diagnosis of Acute Myelogenous Leukemia (AML) or Chronic Myelomonocytic Leukemia (CMML).
• Previous treatment for HR MDS with chemotherapy or other antineoplastic agents, including hypomethylating agents (HMAs), such as decitabine or azacitidine. Previous treatment is permitted with hydroxyurea and with lenalidomide, except that lenalidomide may not be given within 8 weeks before the first dose of study drug(s).
• Have known hypersensitivity to pevonedistat or its excipients.
• Have known hypersensitivity to oral decitabine and cedazuridine or its excipients.
• Diagnosed or treated for another malignancy within 2 years before enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone resection.
• Participants with either clinical evidence of or history of central nervous system (CNS) involvement.
• Are known hepatitis B surface antigen seropositive, or known or suspected active hepatitis C infection. (Note: Participants who have isolated positive hepatitis B core antibody \[i.e., in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody\] must have an undetectable hepatitis B viral load. Participants with history of hepatitis C virus \[HCV\] infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.)
• Have known hepatic cirrhosis or severe pre-existing hepatic impairment.
• Have positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that is laboratory confirmed by a reverse transcription polymerase chain reaction (RT-PCR) test at screening. Testing related to coronavirus disease 2019 (COVID-19) must be performed according to institutional policy and/or per local regulatory guidelines.
• Participants who have had a known infection of SARS-CoV-2 or COVID-19 are permitted if COVID-19 RT-PCR test is negative prior to the screening visit and they present with no symptoms. Participants with documented vaccination history for COVID-19 do not need to be tested, unless they are symptomatic, according to institutional policy and/or local regulatory guidelines.

Sponsors & Collaborators

• Takeda: lead

Related Links

• To obtain more information on the study, click here/on this link

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

pevonedistat; Decitabine; cedazuridine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2021
• First Posted: August 2, 2021
• Study Start: October 1, 2021
• Primary Completion: January 8, 2024
• Study Completion: November 8, 2024
• Last Updated: September 29, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.