Proliferative Chronic Myelomonocytic Leukemia (CMML) MedDRA version: 19.1 Level: LLT Classification code 10054350 Term: Chronic myelomonocytic leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: DACOGEN
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: DECITABINE
CAS Number: 2353-33-5
Current Sponsor code: DAC
Other descriptive name: Dacoge
Sponsors
Groupe Francophone des Myélodysplasies (GFM)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A/ Age = 18 B/ CMML diagnosis according to WHO criteria - Stable excess in blood monocytes, > 1 G/L and accounting for > 10% WBC - Lack of bcr-abl rearrangement (or Philadelphia chromosome). There should be at least one BCR-ABL test (cytogenetics or molecular biology) dating from the date of CMML diagnosis up to date of screening. - Bone marrow blast cells = 5 % - Clonal cytogenetic abnormality (other than t(5;12) (q33; p13) and isolated loss of Y chromosome ) - Anemia (Hb 16 G/l (in absence of infection) - Thrombocytopenia (platelet count 5 cm below costal margin (spleen size should also be measured by an imaging technique) Or: D2/ Extramedullary involvement: Including documented cutaneous, pleural or pericardial effusion. E/ No prior treatment (except supportive care, or ESA, or short term (< 6 weeks before the screening date) HY in patients presenting with high WBC counts). The 6-week period for HY treatment can be prolonged to no more than 8 weeks in patients to allow complete exclusion of donor availability in patients fit for allogeneic stem cell transplantation lacking sibling donors. F/ Performance status 0-2 on the Eastern Cooperative Oncology Group (ECOG) Scale. G/ Adequate organ function including the following - Hepatic : total bilirubin < 1.5 times upper limit of normal (ULN) (except moderate unconjugated hyperbilirubinemia due to intra medullary hemolysis or Gilbert syndrome) , alanine transaminase (ALT) and aspartate transaminase (AST) < 3xULN - Renal : serum creatinine < 2 x ULN H/ Signed Informed consent I/ Negative pregnancy and adequate contraception (including in male patients wishing to father) if relevant. Female subjects of chilbearing potential* must: * A female patient or a female partner of a male patient is considered to have childbearing potential unless she meets at least one of the following criteria: - Age = 50 years and naturally amenorrhoeic for = 1 year (amenorrhoea following cancer therapy does not rule out childbearing potential) - Premature ovarian failure confirmed by a specialist gynaecologist - Previous bilateral salpingo-oophorectomy, or hysterectomy - XY genotype, Turner syndrome, uterine agenesis. Agree to have a medically supervised pregnancy test on the day of the study visit or in the 3 days prior to the study visit once the subject has been on effective contraception for at least 4 weeks. This requirement also applies to women of childbearing potential who practice complete and continued abstinence. The test should ensure the subject is not pregnant when she starts treatment. Agree to have a medically supervised pregnancy test every 4 weeks including 4 weeks after the end of study treatment, except in the case of confirmed tubal sterilization. These pregnancy tes
Exclusion criteria
Exclusion criteria: -Myeloproliferative / myelodysplastic syndrome other than CMML -Patients eligible for allogeneic bone marrow transplantation with an identified donor -CMML with t(5 ;12) or PDGF?R rearrangement that may be treated with imatinib -Pregnant or breastfeeding -Performance status > 2 on the ECOG Scale. -Serious concomitant systemic disorder, including 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 stud -Prior malignancy (except in situ cervix carcinoma, limited basal cell carcinoma, or other tumors if not active during the last 3 years)
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall Survival (OS), defined as the time between study entry and the date of last visit or death. Cumulative incidence of AML, according to WHO criteria (>20% blasts in peripheral blood or bone marrow), and corresponding to an increase by at least 50% compared to peripheral and bone marrow blast count at study entry. Overall and Complete Response Rates at 3 and 6 cycles according to IWG 2006 criteria ;Timepoint(s) of evaluation of this end point: - Overall Survival - Cumulative incidence of AML - Overall and Complete Response Rates | — |
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To compare between the two arms: •Overall Survival •Cumulative AML progression •Overall and Complete Response Rates at 3 and 6 cycles •Response duration •Toxicity (hematological and non hematological) •Health Care Resource usage •Prognostic factors of response and overall survival with DAC and HY, using in particular: -The Spanish-Italian, the German and the French published prognostic scores -Somatic mutations ;Primary end point(s): The primary endpoint of the study is Event-Free Survival , defined as the time between study entry and the date of last visit or the date of the first event occurring. Events will include: - Death from any cause - Blast progression after at least 6 cycles of treatment: doubling of bone marrow blasts to > 10% , and worsening of cytopenias (any of the following) lasting for > 4 weeks: o At least 50% decrement from baseline or maximum response in granulocytes or platelets or o In case of RBC transfusion independence prior to randomization: reduction in Hgb by 2 g/dL or RBC transfusion dependence = 4 RBC units / 8 weeks or - In case of RBC transfusion dependence prior to randomization: increase in RBC transfusion dependence by = 4 RBC units / 8 weeks compared to baseline. - Transformation to AML according to WHO criteria (>20% blasts in peripheral blood or bone marrow) and corresponding, for bone marrow, to an increase by at least 50% compared to bone marrow blast count at study entry. | — |
Countries
Germany, Italy
Contacts
Public ContactDirectrice du GFM
Groupe Francophone des Myélodysplasies (GFM)
Outcome results
None listed