- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02214407
Randomized Phase III Study of Decitabine +/- Hydroxyurea (HY) Versus HY in Advanced Proliferative CMML (GFM-DAC-CMML)
A Randomized Phase III Study of Decitabine (DAC) With or Without Hydroxyurea (HY) Versus HY in Patients With Advanced Proliferative Chronic Myelomonocytic Leukemia (CMML)
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
Study Overview
Detailed Description
ARM A: DECITABINE (DAC)
Decitabine (DAC) will be administered at 20 mg/m2 intravenously daily for 5 days every 28 days.
Treatment will be delayed at the discretion of the investigator (up to D56) for febrile neutropenia (≥ 38.5°C; absolute neutrophil count [ANC], < 1,000/μL), clinical and/or microbiologic infection with grade 3 to 4 neutropenia (ANC < 1,000/μL), or hemorrhage with grade 4 thrombocytopenia (< 25,000 platelets/μL). If renal or hepatic dysfunction occurs, treatment will be stopped until resolution or withheld if dysfunction persists more than 4 days. Persistent grade 4 thrombocytopenia or neutropenia beyond D49 will mandate bone marrow evaluation.
Treatment will be continued until an event is reached. Events and thus study exit will be acknowledged only after agreement between the investigator and a Trial Committee.
Allopurinol, 300mg/d, will be started at the time of inclusion; hydration during treatment will be administered to all patients. In (the rare) case of necessity, prophylactic anti-emetics could be given.
Hydroxyurea may be added during the first 3 cycles if WBC counts > 30 G/L, and mandatory if WBC > 50 G/L. The daily dose will be adapted to maintain WBC below 15 to 20 G/L.
ARM B: HYDROXYUREA (HY)
Hydroxyurea (HY) 1g/d once daily, with dose adjustments (up to 4g/d) to maintain a WBC count between 5 and 10 G/L. Allopurinol, 300mg/d started at the time of inclusion will be administered to all patients.
Treatment will be continued until an event is reached. Events and thus study exit will be acknowledged only after agreement between the investigator and a Trial Committee. This is intended to prevent early dropout, notably in the HY arm.
Dose escalation will be performed by steps of 0.5 g/d, up to 4 g/d, if the WBC has been reduced by less than 20% and remains > 15 G/L. HY will then be adapted to maintain a WBC count between 5 and 10 G/L. HY will be lowered if platelets decrease by > 30 X 109/L (if initially below 100 X 109L). HY will be discontinued in cases of grade 4 thrombocytopenia or neutropenia, and reintroduced at a lower dose after recovery to grade ≤ 3. Persistent grade 4 thrombocytopenia or neutropenia after a 4 week discontinuation will mandate bone marrow evaluation.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
-
Amiens, France, 80054
- CHU Amiens
-
Angers, France, 49 000
- CHU d'Angers
-
Argenteuil, France, 95107
- CH Victor Dupouy
-
Avignon, France, 84000
- Ch Avignon
-
Bayonne, France, 64100
- Centre Hospitalier de la Côte Basque
-
Belfort, France, 90015
- Hôpital Nord Franche-Comté
-
Bobigny, France, 93009
- Hôpital Avicenne
-
Brest, France, 29609
- Chu de Brest - Hôpital Morvan
-
Caen, France, 14033
- CHU côte de Nacre
-
Cesson-Sévigné, France, 35510
- Hôpital Privé Sévigné
-
Clermont-Ferrand, France, 63058
- CHU Estaing
-
Compiègne, France, 60321
- CH de Compiègne
-
Corbeil-Essonnes, France, 91106
- Centre Hospitalier Sud-Francilien
-
Créteil, France, 94010
- Centre Henri Mondor
-
Grenoble, France, 38043
- CHU Albert Michallon
-
Le Mans, France, 72000
- Clinique Victor Hugo
-
Le Mans, France, 72000
- CH Le Mans
-
Lille, France, 59020
- Hôpital Saint Vincent de Paul
-
Limoges, France, 87046
- CHRU de Limoges
-
Lyon, France, 69495
- Centre Hospitalier Lyon Sud
-
Marseille, France, 13009
- Institut Paoli-Calmette
-
Meaux, France, 77100
- Centre Hospitalier de Meaux
-
Montpellier, France, 34295
- Hopital Saint Eloi
-
Montpellier, France, 34000
- Clinique BEAUSOLEIL
-
Nantes, France, 44093
- Hopital de l'Hotel Dieu
-
Nice, France, 06202
- Hopital Archet I
-
Nîmes, France, 30029
- CHU de Nimes
-
Orléans, France, 45067
- CHR d'Orléans
-
Paris, France, 75475
- Hopital St Louis T4
-
Perpignan, France, 66046
- Centre Hospitalier Joffre
-
Pessac, France, 33604
- CHU de Haut-Lévèque
-
Poitiers, France, 86021
- CHU Poitiers
-
Pontoise, France, 95000
- CH René Dubos
-
Pringy, France, 74374
- CH Annecy Genevois
-
Reims, France, 51092
- CHU de Reims
-
Rennes, France, 35033
- CHU Pontchaillou
-
Rouen, France, 76038
- Centre Henri Bequerel
-
Strasbourg, France, 67098
- Hôpital Hautepierre
-
Toulouse, France, 31059
- IUCT Oncopole
-
Toulouse, France, 31059
- IUCT Oncopole - Département d'hématologie
-
Valence, France, 26953
- CH Valence
-
Vandœuvre-lès-Nancy, France, 54511
- CHU Brabois
-
Villejuif, France, 94805
- Institut Gustave Roussy
-
-
La Réunion
-
Saint-Denis, La Réunion, France, 97400
- CHU La Réunion - Site nord
-
Saint-Pierre, La Réunion, France, 97410
- CHU La Réunion-Site Sud
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: ARM A: DECITABINE (DACOGEN)
Decitabine (DAC) will be administered at 20 mg/m2 intravenously daily for 5 days every 28 days. Allopurinol, 300mg/d, will be started at the time of inclusion; hydration during treatment will be administered to all patients. In (the rare) case of necessity, prophylactic anti-emetics could be given. Hydroxyurea may be added during the first 3 cycles if WBC counts > 30 G/L, and mandatory if WBC > 50 G/L. The daily dose will be adapted to maintain WBC below 15 to 20 G/L. |
Decitabine (DAC) will be administered at 20 mg/m2 intravenously daily for 5 days every 28 days. Hydroxyurea may be added during the first 3 cycles if WBC counts > 30 G/L, and mandatory if WBC > 50 G/L. The daily dose will be adapted to maintain WBC below 15 to 20 G/L. Treatment will be continued until an event is reached. Events and thus study exit will be acknowledged only after agreement between the investigator and a Trial Committee.
Other Names:
|
Experimental: ARM B: HYDROXYUREA
Hydroxyurea (HY) 1g/d once daily, with dose adjustments (up to 4g/d) to maintain a WBC count between 5 and 10 G/L. Allopurinol, 300mg/d started at the time of inclusion will be administered to all patients. Dose escalation will be performed by steps of 0.5 g/d, up to 4 g/d, if the WBC has been reduced by less than 20% and remains > 15 G/L. HY will then be adapted to maintain a WBC count between 5 and 10 G/L. HY will be lowered if platelets decrease by > 30 X 109/L (if initially below 100 X 109L). HY will be discontinued in cases of grade 4 thrombocytopenia or neutropenia, and reintroduced at a lower dose after recovery to grade ≤ 3. Persistent grade 4 thrombocytopenia or neutropenia after a 4 week discontinuation will mandate bone marrow evaluation. |
Hydroxyurea (HY) 1g/d once daily, with dose adjustments (up to 4g/d) to maintain a WBC count between 5 and 10 G/L. Allopurinol, 300mg/d started at the time of inclusion will be administered to all patients. Treatment will be continued until an event is reached. Events and thus study exit will be acknowledged only after agreement between the investigator and a Trial Committee. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
compare between the two arms Event-free Survival (EFS)
Time Frame: 3 months
|
Comparison of Event-free Survival between both arms. Events will include
|
3 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival (OS)
Time Frame: 7 month
|
Overall survival compared between both Arm of treatment (decitabine and hydroxyurea)
|
7 month
|
Cumulative incidence of AML
Time Frame: 7 month
|
Comparaison of Cumulative incidence of AML between both arm of treatment (decitabine and hydroxyurea)
|
7 month
|
Overall and Complete Response Rates
Time Frame: 3 month
|
Overall and Complete Response Rates at 3 and 6 cycles according to IWG 2006 criteria modified for CMML
|
3 month
|
Response duration
Time Frame: 3 month
|
Comparison of response duration after 3 month and 6 month of treatment between both arm of treatment (decitabine and hydroxyurea)
|
3 month
|
Toxicity
Time Frame: 1 month
|
hematological and non hematological
|
1 month
|
Prognostic factors
Time Frame: 3 month
|
Prognostic factors of Event Free Survival with decitabine and hydroxyurea
|
3 month
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: ITZYKSON Raphael, PHD, Hopital Saint-Louis, Service hematologie Senior
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- GFM-DAC-CMML
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on MDS
-
Zhejiang Provincial Hospital of TCMUnknown
-
Assiut UniversityUnknown
-
Groupe Francophone des MyelodysplasiesNovartisUnknown
-
Rigshospitalet, DenmarkRecruiting
-
GWT-TUD GmbHRecruiting
-
University Hospital TuebingenRecruiting
-
Montefiore Medical CenterRecruitingAML | MDSUnited States
-
The Second Hospital of Shandong UniversityNot yet recruiting
-
Groupe Francophone des MyelodysplasiesAstex Pharmaceuticals, Inc.Active, not recruiting
-
M.D. Anderson Cancer CenterRecruiting
Clinical Trials on Decitabine
-
Otsuka Beijing Research InstituteRecruitingMyelodysplastic SyndromesChina
-
Chinese PLA General HospitalRecruitingHodgkin Lymphoma | Anti-PD-1 Antibody ResistantChina
-
Astex Pharmaceuticals, Inc.CompletedAcute Myeloid Leukemia | Myelodysplastic Syndromes | Chronic Myelomonocytic LeukemiaUnited States, Canada, Spain, Hungary, Austria, Czechia, France, Germany, Italy, United Kingdom
-
Roswell Park Cancer InstituteNational Comprehensive Cancer NetworkRecruitingCastration-Resistant Prostate Carcinoma | Stage IV Prostate Cancer AJCC v8 | Stage IVA Prostate Cancer AJCC v8 | Stage IVB Prostate Cancer AJCC v8United States
-
M.D. Anderson Cancer CenterGenentech, Inc.; Astex Pharmaceuticals, Inc.RecruitingChronic Myelomonocytic Leukemia | Myelodysplastic SyndromeUnited States
-
Shandong UniversityUnknownMyelodysplastic SyndromesChina
-
M.D. Anderson Cancer CenterRecruitingAcute Myeloid Leukemia | Recurrent Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
-
M.D. Anderson Cancer CenterActive, not recruitingRecurrent Acute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Recurrent Acute Biphenotypic Leukemia | Refractory Acute Biphenotypic LeukemiaUnited States
-
Eisai Inc.TerminatedMyelodysplastic SyndromesUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI); Astex Pharmaceuticals, Inc.RecruitingChronic Phase Chronic Myelogenous Leukemia | Philadelphia Chromosome Positive | BCR-ABL1 Positive Chronic Myelogenous Leukemia | BCR-ABL1 PositiveUnited States