Treatment of MDS/AML patients with an impending hematological relapse with azacitidine alone or in combination with pevonedistat

Phase 1

• Conditions: Acute myeloid leukemia (AML) and Myelodysplastic syndromes (MDS) with impending hematological relapse; MedDRA version: 21.1Level: PTClassification code 10000880Term: Acute myeloid leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10028533Term: Myelodysplastic syndromeSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2019-004536-37-DE
• Lead Sponsor: eipzig University

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-06-16
• Study Completion: 2023-01-31
• Last Update Posted: 24 June 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 14

Inclusion Criteria

- AML or MDS
- continuing first CR after conventional intensive chemotherapy OR continuing CR after alloSCT
- MRD positivity (assessed by local lab) as defined by:
o NPM1mut status >1% in peripheral blood or bone marrow in NPM1 mutated patients at diagnosis or
o Patients after allogeneic transplantation, who were NPM1 unmutated at diagnosis and have a blood or marrow CD34/CD117 chimerism <80%
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 76
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 26

Exclusion Criteria

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:
o Absolute neutrophil count (ANC) < 1.5 Gpt/L
o Platelets < 100 Gpt/L
o Albumin < 2.7 g/dL
o Creatinine clearance < 30 mL/min (Cockcroft und Gault formula)
o Total bilirubin > 1.5xupper limit of normal (ULN)19 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.
o Both Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 3.0 ULN
- ECOG performance status of =2

Concomitant Diseases
- Liver cirrhosis or severe pre-existing hepatic impairment
- Known severe cardiopulmonary disease (e.g. unstable angina, congestive heart failure NYHA III or IV, myocardial infarction within 6 months prior to screening, symptomatic cardiomyopathy, clinically significant arrhythmia20, clinically significant pulmonary hypertension requiring pharmacologic therapy)
- Uncontrolled high blood pressure (i.e. systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg)
- Known prolonged rate corrected QT interval = 500 msec, calculated according to institutional guidelines
- Known left ventricular ejection fraction < 50% as assessed by echocardiogram or radionuclide angiography
- Known moderate to severe symptomatic chronic obstructive pulmonary disease, interstitial lung disease, or pulmonary fibrosis
- Active uncontrolled infection or severe infectious disease, such as severe pneumonia, meningitis, or septicemia
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Known Human Immunodeficiency Virus (HIV 1/2 antibodies)
- Known active Hepatitis B (i.e. HBsAg reactive) or Hepatitis C (i.e., HCV RNA [qualitative] is detected). NOTE: Patients 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. Patients who have positive hepatitis C antibody may be included if they have an undetectable hepatitis C viral load.
- Major surgery within 14 days of randomization or a scheduled surgery during study period
- Known central nervous system (CNS) involvement
- Diagnosis or treatment for another malignancy within 2 years before randomization. (NOTE: Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone resection. Prior diagnosis of myelodysplasia, myeloproliferative neoplasm, or aplastic anemia and treatment for that diagnosis does not lead to exclusion)
- Any evidence of residual disease of another malignancy
- Patients with uncontrolled coagulopathy or bleeding disorder
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the in the best interest of the subject to participate, in the opinion of the treating investigator

Prior unfavourable effect of HMA monotherapy
- Prior HMA failure
- Prior HMA treatment without subsequent allogeneic transplantation

Interfering Treatments
- An

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified