VENETOCLAX for Chronic myelomonocytic leukemia (higher‑risk CMML)

Inclusion criteria

• {"criterion_text":"- Age 18 and older"}
• {"criterion_text":"- CMML diagnosis according to ICC 2022 criteria"}
• {"criterion_text":"- Intermediate-2 or high risk according to the molecular CMML Prognostic Scoring System (CPSS-mol, Elena Blood 2016)"}
• {"criterion_text":"- No prior treatment with HMAs. Prior treatment with Erythropoiesis Stimulating Agents (ESA) is allowed with a > 15 days washout from ESAs. Prior treatment with hydroxurea (HY) is acceptable."}
• {"criterion_text":"- ECOG Performance status 0-2"}
• {"criterion_text":"- Adequate organ function: total bilirubin < 2 times upper limit of normal (ULN), ALT and AST < 3 times ULN, creatinine clearance > 30 mL/min."}
• {"criterion_text":"- Signed Informed Consent Form"}
• {"criterion_text":"- Negative pregnancy and adequate contraception (including in male patients) if relevant"}
• {"criterion_text":"- Affiliation to a health insurance system"}

Exclusion criteria

• {"criterion_text":"- Myeloproliferative / myelodysplastic syndrome other than CMML"}
• {"criterion_text":"- Malabsorption syndrome or other condition that precludes an enteral route of administration"}
• {"criterion_text":"- Previous therapy with a hypomethylating agent for CMML or any antecedent condition"}
• {"criterion_text":"- Previous therapy with a BH3 mimetic"}
• {"criterion_text":"- Antecedent allogeneic stem cell transplantation (HSCT) for CMML or an antecedent of hematological malignancy. Those never transplanted but eligible for HSCT are eligible for the trial."}
• {"criterion_text":"- Subjects referred to in Articles L1121-5 to L1121-8-1 and L1122-1-2 of the Public Health Code"}
• {"criterion_text":"- Bone marrow or peripheral blood blasts (including promonocytes) ≥ 20%"}
• {"criterion_text":"- CMML with t(5;12) or PDGFRß rearrangement that may be treated with imatinib"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Pregnant or breastfeeding"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Medical condition requiring therapies with CYP3A strong or moderate inducing or inhibiting activity at screening"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- Known positive test for human immunodeficiency virus (HIV)"}

Primary endpoints

• {"endpoint_text":"- Safety run-in: dose-limiting toxicity occurring within the first two cycles of treatment","definition_or_measurement_approach":"Dose-limiting toxicity events occurring within the first two treatment cycles (safety run-in assessment)."}
• {"endpoint_text":"- Phase II: Overall response rate (ORR) after 3 and 6 cycles according to protocol-defined criteria modified from MDS/MPN IWG criteria (Savona Blood. 2015 Mar 19; 125(12): 1857–1865). Overall response includes complete remission (CR), partial remission (PR), marrow response (MR) and clinical benefit (CB).","definition_or_measurement_approach":"ORR measured after 3 and 6 cycles using protocol-defined modified MDS/MPN IWG criteria (Savona 2015); overall response comprises CR, PR, MR and CB as defined by those modified criteria."}

Secondary endpoints

• {"endpoint_text":"- CR rate after 3 and 6 cycles according to modified MDS/MPN IWG criteria","definition_or_measurement_approach":"Complete remission rate assessed after 3 and 6 cycles using modified MDS/MPN IWG criteria."}
• {"endpoint_text":"- ORR at best response according to modified MDS/MPN IWG criteria","definition_or_measurement_approach":"Overall response rate at best observed response using modified MDS/MPN IWG criteria."}
• {"endpoint_text":"- ORR after 3 and 6 cycles, and at best response according to DACOTA response criteria (ie modified MDS IWG 2006 criteria, Braun Blood 2011)","definition_or_measurement_approach":"ORR assessed at specified timepoints and best response using DACOTA response criteria (modified MDS IWG 2006 criteria)."}
• {"endpoint_text":"- Duration of Response (according to modified MDS/MPN IWG criteria)","definition_or_measurement_approach":"Duration of response measured per modified MDS/MPN IWG criteria."}
• {"endpoint_text":"- Safety profile (both hematological and non-hematological) of venetoclax in combination with azacitidine","definition_or_measurement_approach":"Safety assessments capturing hematological and non-hematological adverse events; specific measurement details not provided in dataset."}
• {"endpoint_text":"- Overall Survival (OS)","definition_or_measurement_approach":"Overall survival as an outcome; specific censoring rules or calculation method not detailed in provided data."}
• {"endpoint_text":"- AML-free survival (AMLFS)","definition_or_measurement_approach":"AML-free survival; definition details not provided beyond endpoint title."}
• {"endpoint_text":"- Progression-free survival (PFS)","definition_or_measurement_approach":"Progression-free survival; specific definition not provided in dataset."}
• {"endpoint_text":"- Event-free survival (EFS)","definition_or_measurement_approach":"Event-free survival; specific definitions not provided."}
• {"endpoint_text":"- Cumulative incidence of AML and cumulative risk of death without AML","definition_or_measurement_approach":"Cumulative incidence analyses for AML transformation and competing risk of death without AML; detailed statistical approach not provided."}
• {"endpoint_text":"- Cumulative incidence of progressive disease (or AML transformation) and cumulative risk of death without progression or AML transformation","definition_or_measurement_approach":"Cumulative incidence analyses for progression/AML transformation and competing risk of death; detailed methods not included."}
• {"endpoint_text":"- Rate of HSCT and post-HSCT OS and AMLFS","definition_or_measurement_approach":"Rate of hematopoietic stem cell transplantation and post-HSCT overall survival and AML-free survival; measurement specifics not provided."}
• {"endpoint_text":"- OS, AMLFS and PFS censoring at HSCT","definition_or_measurement_approach":"Survival endpoints measured with censoring at HSCT as specified; full censoring rules not included in provided data."}
• {"endpoint_text":"- Rate and description of subsequent therapy","definition_or_measurement_approach":"Descriptive reporting of subsequent therapies; specifics not provided."}
• {"endpoint_text":"- OS, AMLFS and PFS censoring at subsequent therapy","definition_or_measurement_approach":"Survival endpoints measured with censoring at initiation of subsequent therapy; detailed rules not provided."}

France

Earliest CTIS Part Ii Submission Date

14-09-2024

Latest Decision Or Authorization Date

01-04-2025

Processing Time Days

199

Number Of Sites

24

Number Of Participants

44

Primary sponsor

Full Name

Groupe Francophone Des Myelodysplasies

Organisation Type

Patient organisation/association

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"AbbVie","duties_or_roles":"Source of monetary support","organisation_type":""}