Treatment of MDS/AML Patients With an Impending Hematological Relapse With AZA or ATA and Pevonedistat

NCT04712942 | Completed Phase 2

• 1 other identifier: SHAPE
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 14

Brief Summary

MDS/AML with MRD and impending relapse after allogeneic stem cell transplantation and/or conventional chemotherapy

Conditions

Acute Myeloid Leukemia in Remission; Myelodysplastic Syndromes; Minimal Residual Disease

Outcome Measures

Primary Outcomes (1)

• Measurable residual disease (MRD) status after 3 months of treatment

  To show that pevonedistat and azacitidine are more effective compared to azacitidine alone with regard to achievement of MRD negativity after 3 months of treatment. MRD assessment is carried out as determination of the NPM1mut status or as CD34/CD117 chimerism analysis.

  3 months after start of treatment

Secondary Outcomes (4)

• Overall Survival

  From date of randomization until the date of death from any cause, assessed up to 25 months

• Relapse Free Survival

  Time from randomization until hematological relapse or death from any cause (whichever comes first), assessed up to 25 Months.

• Impact of treatment assessed by using the validated questionnaires EORTC QLQ-C30.

  Time from randomization until hematological relapse or death from any cause (whichever comes first)

• Impact of treatment assessed by using the validated questionnaires EQ-5D-5L.

  Time from randomization until hematological relapse or death from any cause (whichever comes first), assessed up to 25 months.

Study Arms (2)

pevonedistat + azacitidine

EXPERIMENTAL

pevonedistat in combination with azacitidine

Drug: Pevonedistat; Drug: Azacitidine

azacitidine monotherapy

OTHER

administration of azacitidine monotherapy

Drug: Azacitidine

Interventions

Pevonedistat DRUG

Patients receive pevonedistat at 20 mg/m2 i.v. (d1,3,5, q4w) up to 12 cycles

pevonedistat + azacitidine

Azacitidine DRUG

azacitidine is given at a standard dose of 75 mg/m² (d1-7 or 1-5,8,9, q4w) up to 12 cycles

azacitidine monotherapy; pevonedistat + azacitidine

Eligibility Criteria

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

You may qualify if:

• AML or MDS
• continuing first CR after conventional intensive chemotherapy OR continuing CR after alloSCT
• Confirmed MRD positivity (assessed by central lab) as defined by:
• NPM1mut status \>1% in peripheral blood or bone marrow in NPM1 mutated patients at diagnosis or
• Patients after allogeneic transplantation, who were NPM1 unmutated at diagnosis and have a blood or marrow CD34/CD117 chimerism \<80%

You may not qualify if:

• Compliance with major study procedures
• Patient does not accept bone marrow sampling during screening, primary end point visit and after the treatment.
• Patient does not accept several blood sampling during screening, treatment (up to bi-daily) and after the treatment.
• Safety
• Inadequate organ function as defined in the list below:
• White blood cell (WBC) count \> 50 Gpt/L before administration of pevonedistat on Cycle 1 Day 1
• Absolute neutrophil count (ANC) \< 1.5 Gpt/L
• Platelets \< 100 Gpt/L
• Albumin \< 2.7 g/dL
• Creatinine clearance \< 30 mL/min (Cockcroft und Gault formula)
• Total bilirubin \> 1.5xupper limit of normal (ULN) except in patients with Gilbert's syndrome. Patients with Gilbert's syndrome may be enrolled if direct bilirubin \> 1.5x ULN of the direct bilirubin.
• Both Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \> 3.0 ULN
• ECOG performance status of ≥2
• Concomitant Diseases
• Hematological relapse

Sponsors & Collaborators

• University of Leipzig: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (14)

Medizinische Klinik IV - Hämatologie und Onkologie, Universitätsklinikum Aachen

Aachen, 52074, Germany

Location

Zentrum Hämatologie, Onkologie, Palliativmedizin, Helios Klinikum Berlin-Buch GmbH

Berlin, 13125, Germany

Location

Klinik für Innere Medizin III, Hämatologie, Onkologie, Stammzelltransplantation, Klinikum Chemnitz gGmbH

Chemnitz, 09113, Germany

Location

Hämatologie/Internistische Onkologie, Onkologische Tagesklinik

Cottbus, 03048, Germany

Location

Medizinischen Klinik und Poliklinik I / Hämatologie, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

Dresden, 01304, Germany

Location

Klinik für Hämatologie, Universitätsklinikum Essen

Essen, 45147, Germany

Location

Universitätsklinik und Poliklinik für Innere Medizin IV, Onkologie, Hämatologie, Universitätsklinikum Halle (Saale)

Halle, 06120, Germany

Location

Klinik und Poliklinik für Innere Medizin II/Hämat. - Onkologie, Universitätsklinikum Jena

Jena, 07740, Germany

Location

Klinik für Innere Medizin II/ Hämatologie und Onkologie, Univ.Klinikum Schleswig-Holstein/Campus Kiel

Kiel, 24105, Germany

Location

Medizinische Klinik und Poliklinik I - Hämatologie und Zelltherapie, Hämostaseologie, Leipzig University

Leipzig, 04103, Germany

Location

Innere Medizin A/Hämatologie-Onkologie, Universitätsklinik Münster

Münster, 48149, Germany

Location

Klinik Innere Medizin III - Onko-, Häma- u. Palliativmedizin, Diakonie-Klinikum Schwäbisch Hall gGmbH

Schwäbisch Hall, 74523, Germany

Location

Klinik für Hämatologie, Onkologie & Stammzelltherapie, Helios-Klinikum Schwerin

Schwerin, 19049, Germany

Location

Abteilung für Hämatologie, Onkologie und Palliativmedizin, Robert-Bosch-Krankenhaus Stuttgart

Stuttgart, 70376, Germany

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Neoplasm, Residual

Interventions

pevonedistat; Azacitidine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Uwe Platzbecker, Prof. Dr.

  University Leipzig

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Model Details: With Cross-Over option

Study Record Dates

• First Submitted: December 18, 2020
• First Posted: January 19, 2021
• Study Start: January 1, 2021
• Primary Completion: January 31, 2023
• Study Completion: January 31, 2023
• Last Updated: August 21, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (14)