Clinical trial NCT01098084: Decitabine in Patients With Chronic Myelomonocytic Leukemia (CMML)
Official title: A Phase II Study of Decitabine in Patients With Chronic Myelomonocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Myelomonocytic Leukemia
Keywords: Decitabine, chronic myelomonocytic leukemia
Lead sponsor: Groupe Francophone des Myelodysplasies
Sponsor class: OTHER
Collaborators: name: Janssen-Cilag Ltd.
First posted: 2010-04-02
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: The aim of this study is to determine the therapeutic efficacy of Decitabine in patients with chronic myelomonocytic leukemia (CMML) diagnosis according to WHO criteria either untreated or previously treated with Hydrea or Etoposide (given orally), non intensive chemotherapy or intensive chemotherapy given more than 3 months before inclusion.


Eligibility criteria: Inclusion Criteria:

* Age 18 or older
* CMML diagnosis according to WHO criteria
* Stable excess in blood monocytes,\>1x10G/l and \>10% of WBC
* Bone marrow blasts \<20%
* Dysplasia of at least one lineage or clonality marker or blood monocytosis during more than 3 months w/o other explanation
* With:

  * if WBC \< or= 12 000/mm3: IPSS high or intermediate 2
  * if WBC \> 12 000/mm3: at least two of the following criteria: blast cells \> 5% in the bone marrow, clonal cytogenetic abnormality other than t(5;12)(q33;p13), anemia (Hb \< 100 g/l), thrombocytopenia (platelet count \< 100G/l), splenomegaly \> 5 cm below costal margin, extramedullary localization
* Either untreated or previously treated with
* Hydrea or Etoposide given orally
* non intensive chemotherapy
* intensive chemotherapy given more than 3 months before inclusion
* With performance status 0-2 on the ECOG scale
* With estimated life expectancy of at least 12 weeks
* With adequate organ function including the following:

  * Hepatic: total bilirubin \< 1.5 times upper limit of normal (ULN), alanine transaminase (ALT) and aspartate transaminase (AST) \< 3 times ULN
  * Renal: serum creatinine \< 1.5 times ULN, creatinine clearance \> 30 ml/min
* With informed consent
* Negative pregnancy and adequate contraception if relevant

Exclusion Criteria:

* Myeloproliferative/myelodysplastic syndrome other than CMML
* Acute blastic transformation of CMML with bone marrow blasts\>20%
* Patients eligible for allogenic bone marrow transplantation with identified donor
* CMML with t(5;12) or PDGFbetaR rearrangement that could receive Imatinib
* Previous treatment with a hypomethylating agent
* Age \< 18 years old
* Pregnancy or breastfeeding
* Performance status\> 2 on the ECOG Scale
* Estimated life expectancy \< 12 weeks
* 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

Primary outcomes:
measure: To determine response of patients with CMML to 6 courses of Decitabine according to IWG 2006 criteria, adapted for CMML with WBC>12000/mm3
Secondary outcomes:
measure: Response duration
measure: Time to progression to AML
measure: Survival
measure: Toxicity (hematological and non-hematological)
Other outcomes:
Locations:
city: Le Kremlin-Bicêtre
country: France
facility: CHU de Bicêtre
state: Ile de France
city: Amiens
country: France
facility: CHU d'Amiens
city: Angers
country: France
facility: CH Angers
city: Avignon
country: France
facility: Hôpital Avignon
city: Bayonne
country: France
facility: Hopital de la Cote Basque
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Bordeaux
country: France
facility: CHU Haut-Lévèque
city: Boulogne Sur Mer
country: France
facility: Hôpital Boulogne Sur Mer
city: Clamart
country: France
facility: Hopital d'Instruction des Armées Percy
city: Clermont Ferrand
country: France
facility: CHU de
city: Corbeil-Essonnes
country: France
facility: Centre Hospitalier Sud-Francilien
city: Creteil
country: France
facility: Hopital Henri Mondor
city: Dijon
country: France
facility: CHU de Dijon
city: Le Chesnay
country: France
facility: Hôpital Versailles
city: Le Mans cedex
country: France
facility: Centre Hospitalier du Mans
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Nantes
country: France
facility: CHU de nantes
city: Nice
country: France
facility: Hôpital Archet1
city: Nimes
country: France
facility: CHU Caremeau
city: Orléans
country: France
facility: CHR La Source orléans
city: Paris-Cedex 12
country: France
facility: Hôpital Saint-Antoine.
city: Paris
country: France
facility: Hopital Cochin
city: Paris
country: France
facility: Hopital Necker
city: Paris
country: France
facility: Hopital Hotel Dieu
city: Paris
country: France
facility: Hoiptal St Louis
city: Perpignan
country: France
facility: Centre Hospitalier Joffre
city: Reims
country: France
facility: CHU de Reims
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Toulouse
country: France
facility: Hematology Dpt, Hopital Purpan
city: Tours
country: France
facility: CHU Bretoneau
city: Villejuif
country: France
facility: Institut gustave Roussy
Study officials:
affiliation: Gustave Roussy, Cancer Campus, Grand Paris
name: Eric Solary, MD, PhD
role: STUDY_CHAIR
affiliation: Avicenne Hospital, 93 000 Bobigny
name: Thorsten Braun, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Le Bocage, Dijon
name: Ingrid Lafon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Itzykson R, Kosmider O, Renneville A, Gelsi-Boyer V, Meggendorfer M, Morabito M, Berthon C, Ades L, Fenaux P, Beyne-Rauzy O, Vey N, Braun T, Haferlach T, Dreyfus F, Cross NC, Preudhomme C, Bernard OA, Fontenay M, Vainchenker W, Schnittger S, Birnbaum D, Droin N, Solary E. Prognostic score including gene mutations in chronic myelomonocytic leukemia. J Clin Oncol. 2013 Jul 1;31(19):2428-36. doi: 10.1200/JCO.2012.47.3314. Epub 2013 May 20.
citation: Braun T, Itzykson R, Renneville A, de Renzis B, Dreyfus F, Laribi K, Bouabdallah K, Vey N, Toma A, Recher C, Royer B, Joly B, Vekhoff A, Lafon I, Sanhes L, Meurice G, Orear C, Preudhomme C, Gardin C, Ades L, Fontenay M, Fenaux P, Droin N, Solary E; Groupe Francophone des Myelodysplasies. Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia: a phase 2 trial. Blood. 2011 Oct 6;118(14):3824-31. doi: 10.1182/blood-2011-05-352039. Epub 2011 Aug 9.