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MDSPhase 3GFM-DAC-CMMLNCT02214407

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

A Phase 3 study testing Decitabine and HYDROXYUREA in people with MDS, run by Groupe Francophone des Myelodysplasies at 45 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
MDS
What is being tested?
Decitabine and HYDROXYUREA
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
170 participants
Where
45 sitesFrance
Study dates
14 Oct 2014to 16 Aug 2021
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 12Show fewer
  • 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.

Who cannot join

  • 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)

Trial locations and contacts

45 sites in 1 country.

45 sites in 1 country

France45 sites

  • Chu Amiens

    Amiens, 80054

  • CHU d'Angers

    Angers, 49 000

  • CH Victor Dupouy

    Argenteuil, 95107

  • Ch Avignon

    Avignon, 84000

  • Centre Hospitalier de La Cote Basque

    Bayonne, 64100

  • Hôpital Nord Franche-Comté

    Belfort, 90015

  • Hôpital Avicenne

    Bobigny, 93009

  • CHU de Brest - Hôpital Morvan

    Brest, 29609

  • CHU Côte de Nacre

    Caen, 14033

  • Hôpital privé Sévigné

    Cesson-Sévigné, 35510

  • CHU Estaing

    Clermont-Ferrand, 63058

  • CH de Compiègne

    Compiègne, 60321

  • Centre Hospitalier Sud-Francilien

    Corbeil-Essonnes, 91106

  • Centre Henri Mondor

    Créteil, 94010

  • CHU Albert Michallon

    Grenoble, 38043

  • CH Le Mans

    Le Mans, 72000

  • Clinique Victor Hugo

    Le Mans, 72000

  • Hôpital Saint Vincent de Paul

    Lille, 59020

  • CHRU de Limoges

    Limoges, 87046

  • Centre Hospitalier Lyon Sud

    Lyon, 69495

  • Institut Paoli-Calmette

    Marseille, 13009

  • Centre Hospitalier de Meaux

    Meaux, 77100

  • Clinique Beausoleil

    Montpellier, 34000

  • Hôpital Saint Eloi

    Montpellier, 34295

  • Hopital de l'Hotel Dieu

    Nantes, 44093

  • Hopital Archet I

    Nice, 06202

  • CHU de Nîmes

    Nîmes, 30029

  • CHR d'Orléans

    Orléans, 45067

  • Hopital St Louis T4

    Paris, 75475

  • Centre Hospitalier Joffre

    Perpignan, 66046

  • CHU de Haut-Lévèque

    Pessac, 33604

  • CHU Poitiers

    Poitiers, 86021

  • CH René Dubos

    Pontoise, 95000

  • CH Annecy Genevois

    Pringy, 74374

  • CHU de Reims

    Reims, 51092

  • CHU Pontchaillou

    Rennes, 35033

  • Centre Henri Bequerel

    Rouen, 76038

  • CHU La Réunion - Site nord

    Saint-Denis, La Réunion, 97400

  • CHU La Réunion-Site Sud

    Saint-Pierre, La Réunion, 97410

  • Hôpital Hautepierre

    Strasbourg, 67098

  • IUCT Oncopole - Département d'hématologie

    Toulouse, 31059

  • Iuct Oncopole

    Toulouse, 31059

  • CH Valence

    Valence, 26953

  • CHU Brabois

    Vandœuvre-lès-Nancy, 54511

  • Institut gustave Roussy

    Villejuif, 94805

Other trials in France

About this study

Official title: 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

Read the 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.

Conditions
MDS
Being tested
Decitabine, HYDROXYUREA

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DecitabineDrug

    Also called DACOGEN

    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.

  • HYDROXYUREADrug

    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.

Study groups in NCT02214407
Study groupRoleWhat they receive
ARM A: DECITABINE (DACOGEN)ExperimentalDecitabine (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.
Receives: Drug: Decitabine
ARM B: HYDROXYUREAExperimentalHydroxyurea (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.
Receives: Drug: HYDROXYUREA

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. compare between the two arms Event-free Survival (EFS)

    Comparison of Event-free Survival between both arms. Events will include

    • Death from any cause
    • Disease Progression, defined as one of the following: (i) at any time point: transformation to AML according to WHO criteria ; (ii) after at least 6 cycles of treatment: doubling of bone marrow blasts to > 10%, and worsening of cytopenias lasting for > 4 weeks ; (iii) after at least 3 cycles of treatment: Progression of myeloproliferation (despite maximal HY or DAC dosing; in the absence of concomitant infection) defined as: ≥ 50% increase in spleen size as determined by an imaging technique or doubling in WBC or occurrence of a previously undiagnosed extramedullary localization of the disease.

    Measured: 3 months

Secondary outcomes (6)

  1. Overall Survival (OS)

    Overall survival compared between both Arm of treatment (decitabine and hydroxyurea)

    Measured: 7 month

  2. Cumulative incidence of AML

    Comparaison of Cumulative incidence of AML between both arm of treatment (decitabine and hydroxyurea)

    Measured: 7 month

  3. Overall and Complete Response Rates

    Overall and Complete Response Rates at 3 and 6 cycles according to IWG 2006 criteria modified for CMML

    Measured: 3 month

  4. Response duration

    Comparison of response duration after 3 month and 6 month of treatment between both arm of treatment (decitabine and hydroxyurea)

    Measured: 3 month

  5. Toxicity

    hematological and non hematological

    Measured: 1 month

  6. Prognostic factors

    Prognostic factors of Event Free Survival with decitabine and hydroxyurea

    Measured: 3 month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Aug 2014 (estimated)
  2. Study start14 Oct 2014
  3. Primary completion5 Jul 2021
  4. Study completion16 Aug 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
170 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02214407
Sponsor's protocol ID
GFM-DAC-CMML
Acronym
GFM-DAC-CMML
Status last verified
Nov 2021
First submitted
30 Jul 2014
Last updated
19 Nov 2021
Results posted
No
Data monitoring committee
Yes

Publications

  • Itzykson R, Santini V, Thepot S, Ades L, Chaffaut C, Giagounidis A, Morabito M, Droin N, Lubbert M, Sapena R, Nimubona S, Goasguen J, Wattel E, Zini G, Torregrosa Diaz JM, Germing U, Pelizzari AM, Park S, Jaekel N, Metzgeroth G, Onida F, Navarro R, Patriarca A, Stamatoullas A, Gotze K, Puttrich M, Mossuto S, Solary E, Gloaguen S, Chevret S, Chermat F, Platzbecker U, Fenaux P. Decitabine Versus Hydroxyurea for Advanced Proliferative Chronic Myelomonocytic Leukemia: Results of a Randomized Phase III Trial Within the EMSCO Network. J Clin Oncol. 2023 Apr 1;41(10):1888-1897. doi: 10.1200/JCO.22.00437. Epub 2022 Dec 1.

    PubMed 36455187

  • Pleyer L, Leisch M, Kourakli A, Padron E, Maciejewski JP, Xicoy Cirici B, Kaivers J, Ungerstedt J, Heibl S, Patiou P, Hunter AM, Mora E, Geissler K, Dimou M, Jimenez Lorenzo MJ, Melchardt T, Egle A, Viniou AN, Patel BJ, Arnan M, Valent P, Roubakis C, Bernal Del Castillo T, Galanopoulos A, Calabuig Munoz M, Bonadies N, Medina de Almeida A, Cermak J, Jerez A, Montoro MJ, Cortes A, Avendano Pita A, Lopez Andrade B, Hellstroem-Lindberg E, Germing U, Sekeres MA, List AF, Symeonidis A, Sanz GF, Larcher-Senn J, Greil R. Outcomes of patients with chronic myelomonocytic leukaemia treated with non-curative therapies: a retrospective cohort study. Lancet Haematol. 2021 Feb;8(2):e135-e148. doi: 10.1016/S2352-3026(20)30374-4.

    PubMed 33513373

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Decitabine and HYDROXYUREA in people with MDS, run by Groupe Francophone des Myelodysplasies at 45 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 45 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

compare between the two arms Event-free Survival (EFS) (time frame: 3 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02214407, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2021.

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