Randomized Phase III Study of Decitabine +/- Hydroxyurea (HY) Versus HY in Advanced Proliferative CMML

• Status: Active, not recruiting
• Trial end date: 2021-10-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a phase III, two-arm, randomized, stratified, multicenter, open-label study with individual therapeutic benefit aim:

Decitabine (DAC) with or without Hydroxyurea (HY) versus HY in patients with advanced proliferative Chronic Myelomonocytic Leukemia (CMML)

The primary objective of the study is to compare between the two arms Event-free Survival (EFS).

Secondary objectives are to compare between both arms:

Overall Survival (OS) Cumulative incidence of AML Overall and Complete Response Rates at 3 and 6 cycles according to IWG 2006 criteria modified for CMML Response duration Toxicity (hematological and non hematological) Prognostic factors

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Groupe Francophone des Myelodysplasies
• Collaborator: Janssen-Cilag Ltd.
• Treatments: Allopurinol; Azacitidine; Benzocaine; Decitabine; Hydroxyurea

Criteria

Inclusion Criteria:

• Age ≥ 18

• CMML diagnosis according to WHO criteria Stable excess in blood monocytes, > 1 G/L Lack of bcr-abl rearrangement (or Philadelphia chromosome) Bone marrow blast cells < 20% Dysplasia of at least one lineage or clonality marker or blood monocytosis during more than 3 months w/o other explanation Blood and marrow smears will be reviewed at each country's level, but morphologist meetings at the 3 country level are planned for better harmonization and review of difficult cases

• WBC ≥ 13 G/L Measured on two successive CBC at least two weeks apart, outside of a context of infection.

• Either D1 or D2

D1: At least two of the following criteria, reviewed at each country's level: (modified from Wattel et al. Blood 1996) Marrow blasts >= 5 % Clonal cytogenetic abnormality (other than t(5;12) (q33; p13) and isolated loss of Y chromosome ) Anemia (Hb < 10 g/dL) ANC > 16 G/l (in absence of infection) Thrombocytopenia (platelet count < 100 G/L) Splenomegaly > 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.

• No prior treatment (except supportive care, or ESA, or short term (< 6 weeks) HY in patients presenting with high WBC counts)

• Performance status 0-2 on the Eastern Cooperative Oncology Group (ECOG) Scale.

• 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

• Signed Informed consent

• Negative pregnancy and adequate contraception (including in male patients wishing to father) if relevant.

Exclusion Criteria:

• Myeloproliferative / myelodysplastic syndrome other than CMML

• CMML with t(5 ;12) or PDGFBR rearrangement that may receive imatinib

• Patients eligible for allogeneic bone marrow transplantation with an identified donor

• 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 study

• Prior malignancy (except in situ cervix carcinoma, limited basal cell carcinoma, or other tumors if not active during the last 3 years)