Newly diagnosed, HMA-naïve, higher-risk (HR, defined as CPSS risk intermediate-2 or high) CMML patients MedDRA version: 21.0 Level: LLT Classification code 10054350 Term: Chronic myelomonocytic leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Venclyxto
Product Name: Venclyxto
Product Code: ABT-199
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Venetoclax
CAS Number: 1257044-40-8
Concentration unit: mg milligram(s)
Sponsors
Groupe Francophone des Myélodysplasies (GFM)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1- Age 18 and older. 2- CMML diagnosis according to WHO 2016 criteria. 3- Intermediate-2 or high risk according to the CMML Prognostic Scoring System (CPSS, Such Blood 2013). 4- 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) for 30 mL/min. 7- Signed Informed Consent Form (ICF). 8- Negative pregnancy and adequate contraception (including in male patients) if relevant. 9- Affiliation to a health insurance system. 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 44 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 44
Exclusion criteria
Exclusion criteria: 1- Myeloproliferative / myelodysplastic syndrome other than CMML. 2- Bone marrow or peripheral blood blasts (including promonocytes) = 20%. 3- CMML with t(5;12) or PDGFRß rearrangement that may be treated with imatinib. 4- Unavailable CPSS at inclusion (WBC prior to HY used to compute CPSS at inclusion in HY-exposed patients) or with a CPSS low or intermediate-1 at study entry. 5- Pregnant or breastfeeding. 6- 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. 7- Medical condition requiring therapies with CYP3A strong or moderate inducing or inhibiting activity at screening. 8- 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). 9- Known positive test for human immunodeficiency virus (HIV). 10- Malabsorption syndrome or other condition that precludes an enteral route of administration. 11- Previous therapy with a hypomethylating agent for CMML or any antecedent condition. 12- Previous therapy with a BH3 mimetic. 13- 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy and safety of venetoclax in the study population ;Secondary Objective: To explore potential biomarkers;Primary end point(s): Safety run-in: dose-limiting toxicity occurring within the first two cycles of treatment. 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). ;Timepoint(s) of evaluation of this end point: Safety run in : after cycle 2 Phase II : after 3 and 6 cycles | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): CR rate after 3 and 6 cycles according to MDS/MPN IWG criteria. ORR at best response according to MDS/MPN IWG criteria. ORR after 3 and 6 cycles, and at best response according to DACOTA response criteria (ie modified MDS IWG 2006 criteria, Braun Blood 2011). Duration of Response (according to MDS/MPN IWG criteria). Safety profile (both hematological and non-hematological) of venetoclax in combination with azacitidine. Overall Survival (OS). AML-free survival (AMLFS). Progression-free survival (PFS). Event-free survival (EFS). Cumulative incidence of AML and cumulative risk of death without AML. Cumulative incidence of progressive disease (or AML transformation) and cumulative risk of death without progression or AML transformation. Rate of HSCT and post-HSCT OS and AMLFS. OS, AMLFS and PFS censoring at HSCT. Rate and description of subsequent therapy. OS, AMLFS and PFS censoring at subsequent therapy. ;Timepoint(s) of evaluation of this end point: after LPLV (EOS) | — |
Countries
France
Contacts
Public ContactFatiha CHERMAT
Groupe Francophone des Myélodysplasies (GFM)
Outcome results
None listed