Oral Azacitidine Combined With Venetoclax in Previously Untreated Higher-risk Myelodysplastic Syn… (NCT05782127) | Clinical Trial Compass
Active — Not RecruitingPhase 1/2
Oral Azacitidine Combined With Venetoclax in Previously Untreated Higher-risk Myelodysplastic Syndromes
France36 participantsStarted 2023-12-06
Plain-language summary
This phase I/II open-label, dose-finding, multi-center study will assess safety and primary efficacy of Onureg and Venetoclax combination, to define the optimal biological dose and optimal treatment duration of Onureg to be used along with Venetoclax for further studies in previously untreated patients with higher-risk myelodysplastic syndromes (HR-MDS) not eligible to transplant.
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. Subjects must understand and voluntarily sign and date an ICF indicating the investigational nature of the study, approved by an independent EC/IRB, prior to the initiation of any screening or study-specific procedures.
✓. Age ≥ 18 years at the date of signing the ICF.
✓. Diagnosis of MDS according to the 2016 WHO classification (13) (Appendix 1), with presence of \< 20% bone marrow blasts per bone marrow aspirate at screening, confirmed by local investigator with HR-MDS, based on the revised International Prognostic Scoring System (IPSS-R) \>3 (intermediate, high or very high) (14) (Appendix 2) and a blast percentage of 5 or more.
✓. Previously untreated HR-MDS: no prior therapy for MDS with any hypomethylating agents (azacitidine or decitabine), chemotherapy, allo-Hematopoietic Stem Cell Transplantation (HSCT) or experimental agent. All other treatments are not considered prior therapy.
✓. Not immediately eligible for allo-HSCT or intensive chemotherapy at the time of screening due to individual clinical factors such as age, comorbidities and performance status, donor availability.
✓. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
✓. Total white blood cell (WBC) count ≤ 10 G/L; Treatment with hydroxyurea is permitted to lower the WBC to reach this inclusion criterion and will be stopped at least 48 hours before treatment initiation.
✓. Adequate liver functions as demonstrated by:
Exclusion criteria
✕. Previous treatment for MDS, any approved or investigational antineoplastic agents or radiotherapy.
✕. Participant has an active, uncontrolled systemic fungal, bacterial, or viral infection. The participant should be afebrile and off antibiotics for at least 72 hours and off antifungals for 7 days. In the case of prior SARS-CoV-2 infection, symptoms must have completely resolved and based on Investigator assessment in consultation with the Medical Monitor, there are no sequelae that would place the patient at a higher risk of receiving investigational treatment.
✕. History of clinically significant medical conditions, laboratory abnormality, psychiatric illness or any other reason that the investigator determines would interfere with the subject's participation in this study, would make the subject an unsuitable candidate to receive study drug or predisposes the participant to high risk of noncompliance with the protocol.
✕. History of active malignancy within the past year prior to screening, with the exception of:
✕. Participant has received strong or moderate CYP3A inhibitors or inducers or p-gp inhibitors within 7 days prior to initiation of study treatment with prolonged treatment required without therapeutic alternatives. Azols are the only exception and may be permitted after cycle 1 at investigator's discretion and will result in venetoclax dose reduction.
✕. Consumption of grapefruit products, Seville oranges or starfruit within 3 days prior to first dose of venetoclax.
✕. Received live attenuated vaccines prior to initiation of study treatment.