Azacitidine Combined With Venetoclax in Patients With Higher-risk Chronic Myelomonocytic Leukemia… (NCT05768711) | Clinical Trial Compass
Active — Not RecruitingPhase 2
Azacitidine Combined With Venetoclax in Patients With Higher-risk Chronic Myelomonocytic Leukemia (AVENHIR)
France44 participantsStarted 2023-10-04
Plain-language summary
Open-label phase II, single arm, multicenter study with safety run-in to evaluate the efficacy and safety of Azacitidine combined with Venetoclax in patients with higher-risk chronic myelomonocytic leukemia
Who can participate
Age range18 Years
SexALL
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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
✓. Age 18 and older.
✓. CMML diagnosis according to ICC 2022 criteria.
✓. Intermediate-2 or high risk according to the molecular CMML Prognostic Scoring System (CPSS-mol) at study entry. In patients treated with HY at screening, the white blood count (WBC) prior to introduction of HY will be used to compute CPSS-mol. In patients with failed or missing cytogenetics or genetics at screening, cytogenetics and genetics at CMML diagnosis will be used to compute CPSS-mol.
✓. No prior treatment with hypomethylaing agents, including Azacitidine, decitabine, SGI-110, AST7227 or CC-486 for CMML or any antecedent condition, including antecedent MDS or auto-immune disease. Prior treatment with Erythropoiesis Stimulating Agents (ESA) is allowed with a \> 15 days washout from ESAs. Prior treatment with hydroxyurea (HY) is acceptable. No washout is necessary for those patients but pre-HY WBC will be taken in consideration for CPSS-mol computation.
✓. Performance status 0-2 on the Eastern Cooperative Oncology Group (ECOG) Scale.
✓. Adequate organ function including the following:
✓. Signed Informed Consent Form (ICF).
✓. Negative pregnancy and adequate contraception (including in male patients) if relevant.
Exclusion criteria
✕. Myeloproliferative / myelodysplastic syndrome other than CMML.
✕. Bone marrow or peripheral blood blasts (including promonocytes) ≥ 20%. If both local and central review are available and discrepant, the central review will be used.
What they're measuring
1
Safety run-in
Timeframe: after 2 cycles of treatment of the safety run-in phase patients (each cycle is 28 days)
2
Overall response rate
Timeframe: after 3 and 6 cycles of treatment of the phase II patients (each cycle is 28 days)
✕. CMML with t(5;12) or PDGFRbeta rearrangement that may be treated with imatinib.
✕. Unavailable CPSS-mol at inclusion (WBC prior to HY used to compute CPSS-mol at inclusion in HY-exposed patients) or with a CPSS-mol low or intermediate-1 at study entry.
✕. Pregnant or breastfeeding.
✕. Serious concomitant systemic disorder, including auto-immune or auto-inflammatory disease requiring \> 20 mg/d prednisone equivalent, active bacterial, fungal or viral infection that in the opinion of the investigator, would compromise the safety of the patient and/or his/her ability to complete the study.
✕. Medical condition requiring therapies with CYP3A strong or moderate inducing or inhibiting activity at screening. All strong or moderate CYP3A inducers should be discontinued 7 days prior to the first dose of study drug. All strong or moderate CYP3A inhibitors should be discontinued 3 days prior to the first dose of study drug. A sample list of CYP3A4 inhibitors and inducers is provided in Appendix F.
✕. Prior malignancy (except in situ cervix carcinoma, limited basal cell carcinoma, asymptomatic prostatic cancer not requiring treatment, or other tumors if not active during the last 2 years).