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Myelodysplastic SyndromesPhase 2NCT01015352

Azacitidine Combined to Epoetin Beta in International Prognostic Scoring System (IPSS) Low-risk and Intermediate-1 Myelodysplastic Syndrome (MDS) Patients, Resistant to Erythropoetin-stimulating Agents (ESA)

A Phase 2 study testing Azacitidine and Epoetin beta in people with Myelodysplastic Syndromes, run by Groupe Francophone des Myelodysplasies at 29 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

The study is aimed to treat low-risk MDS patients,who are dependent on red-blood cell transfusion due to disease-related anemia, and who have a proven resistance towards treatment with erythropoetin-stimulating agents (ESA). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelodysplastic Syndromes
What is being tested?
Azacitidine and Epoetin beta
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
98 participants
Where
29 sitesFrance
Study dates
Feb 2009to Mar 2014
Phase
Phase 2
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

  • MDS defined as
  • RCMD, RA with or without ring sideroblasts
  • RAEB 1, or CMML 1, if WBC < 13 G /l according to the WHO classification
  • with a low or int-1 IPSS score AND
  • primary or secondary resistance to epoetin alpha/ beta (> 60000 U/w) or darbepoetin (> 250ug/w), administered for at least 12 weeks
  • requirement of RBC transfusions > 4 U in the previous 8 weeks
Show all 12Show fewer
  • Aged 18 years or more
  • Adequate contraception, if relevant
  • Negative pregnancy test if relevant
  • Written Informed consent
  • Ability to participate to a clinical trial and adhere to study procedures
  • Health insurance

Who cannot join

  • Therapy-related MDS (after chemo- or radiotherapy for a previous neoplasm or immune disorder)
  • Patients with a planned allogeneic bone marrow transplantation
  • Creatininemia >1.5 upper normal value or estimated Ccr less than 30ml/mn
  • ALAT and ASAT >2.5 upper normal value
  • Bilirubin >2N, except unconjugated hyperbilirubinemia due to MDS-related dyserythropoiesis
  • Heart failure NYHA > II
Show all 10Show fewer
  • Known allergy to mannitol
  • Other tumor, unstable for the last three years, except in situ uterine carcinoma or basal skin tumor
  • ECOG > 2
  • Life expectancy less than 3 months

Trial locations and contacts

29 sites in 1 country.

29 sites in 1 country

France29 sites

  • CHU d'Amiens

    Amiens, 80054

  • Hôpital Angers

    Angers, 49033

  • Hôpital Avignon

    Avignon, 84000

  • Hôpital de la Côte Basque

    Bayonne, 64100

  • Hopital Avicenne

    Bobigny, 93009

  • Hôpital Boulogne Sur Mer

    Boulogne-sur-Mer, 62321

  • Hopital Clémenceau

    Caen, 14033

  • Hôpital le Bocage

    Dijon, 21034

  • Hôpital Versailles

    Le Chesnay, 78157

  • Hôpital kremlin Bicêtre

    Le Kremlin-Bicêtre, 94275

  • Hôpital Saint Vincent

    Lille, 59020

  • Hôpital Huriez

    Lille, 59037

  • Hôpital Limoges

    Limoges, 87046

  • Hôpital Edouard Herriot

    Lyon, 69437

  • Hôpital Paoli-Calmettes

    Marseille, 13273

  • Hôpital Brabois

    Nancy, 54511

  • Hôpital Hôtel Dieu

    Nantes, 44035

  • Hôpital Archet1

    Nice, 06202

  • Hôpital La Source

    Orléans, 45067

  • Hôpital Lariboisière

    Paris, 75475

  • Hôpital Saint Louis

    Paris, 75475

  • Hôpital Saint Antoine

    Paris, 75571

  • Hôpital Cochin

    Paris, 75679

  • Hôpital Maréchal Joffre

    Perpignan, 66046

  • Hôpital Jean-Bernard

    Poitiers, 86021

  • Hôpital Reims

    Reims, 51092

  • Hôpital Henri Becquerel

    Rouen, 76038

  • Hôpital Hautepierre

    Strasbourg, 67098

  • Hôpital Purpan

    Toulouse, 31059

Other trials in France

About this study

Official title: A Phase II Study of Azacitidine (Vidaza®) Combined to Epoetin Beta (NeoRecormon®) in IPSS Low-risk and Intermediate-1 MDS Patients, Resistant to ESA

The study is aimed to treat low-risk MDS patients,who are dependent on red-blood cell transfusion due to disease-related anemia, and who have a proven resistance towards treatment with erythropoetin-stimulating agents (ESA). The study randomizes patients to receive a treatment with the demethylating agent 5-azacytidine alone or in combination with an ESA. The study thus evaluates, if efficacy of 5-azacytidine, notably on the red-blood cell transfusion-dependence is comparable/inferior to a combination treatment with azacitidine and an ESA (that is if 5-azacytidine can overcome the resistance towards ESA). Being a phase II study, the study assesses, duration of erythroid response, overall survival and time to progression as well as toxicity.

Read the detailed description

Phase II Study of Azacitidine (Vidaza®) Combined to Epoetin Beta (NeoRecormon®) in IPSS Low-risk and Intermediate-1 MDS Patients, Resistant to ESA

The Primary Endpoint of this study is to determine the major erythroid response rate after 6 courses, assessed according to IWG 2000 criteria.

The Secondary Endpoints are to determine the percentage of major HI-E and minor HI-E after 4 and 6 courses according to IWG 2000, the HI-E IWG 2006 criteria, the duration of erythroid response, the red blood cell transfusion independence at 4 and 6 months, the overall survival and time to IPSS progression and the toxicity (NCI-CTAE).

The trial will enroll 98 patients (49 patients per arm)

Treatment in arm A:

Azacitidine 75mg/sqm SQ per day for 5 days every 28 days for 6 courses Dosing of each subsequent course will be adapted according to extrahematological toxicity and cytopenias.

In responders after 6 courses of azacitidine according to IWG 2000 criteria (both minor and major erythroid responses of HI-E) 12 identical additional maintenance courses will be delivered every 28 days, unless relapse occurs (according to IWG 2000 criteria).

Treatment in arm B:

  • Azacitidine 75mg/sqm SQ per day for 5 days every 28 days for 6 courses. (dosing of each subsequent course will be adapted according to extra hematological toxicity and cytopenias) AND
  • Epoetin beta : 60000U weekly SQ injections Dosing of epoetin beta will be adapted according to current ASH-ASCO guidelines and black box warning of epoetin beta. Epoetin beta therapy may therefore be interrupted, in case of response to azacitidine, as soon as a hemoglobin level of 12g/dl is achieved on two sequential bimonthly blood count measurements.

A 40% dose reduction of epoetin beta will be required if:

  • Hb level rise of 1 g/dl is observed within two weeks
  • Hb level exceeds 11g/dl

In responders after 6 courses of azacitidine + epoetin beta, according to IWG 2000 criteria (both minor and major erythroid responses of HI-E) 12 identical additional maintenance courses of azacitidine will be delivered every 28 days, unless relapse occurs (according to IWG 2000 criteria) Epoetin beta will be administered as described above.

In both arms, each subsequent course will be delivered

  • In absence of persistent grade >2 non-hematological toxicity
  • In absence of rehospitalisation for severe bleeding, infection or febrile neutropenia and non-hematological toxicity following the previous course
  • If neutrophil counts are > 1G/l or > 50% of baseline neutrophil counts
  • If platelets are > 75G/l or > 50% of baseline platelets counts

In case of persistent cytopenia, blood counts will be at least checked every 2 weeks, and the next course delayed until resolution of cytopenia, as defined above.

In case of persistence of cytopenia beyond day 56 of the preceding course, an new evaluation of the disease, using clinical examination, blood and bone marrow examinations +/- cytogenetics will be mandatory before eventually pursuing azacitidine at lower dosing levels.

Being tested
Azacitidine, Epoetin beta
Keywords
Myelodysplastic Syndromes
Medical subject headings
Myelodysplastic Syndromes

What participants receive

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

  • AzacitidineDrug

    Also called Vidaza®

    Azacitidine 75mg/sqm SQ per day for 5 days every 28 days

  • Epoetin betaDrug

    Also called Epoetin beta : 60000U weekly SQ injections

    Epoetin beta : 60000U weekly SQ injections

    NeoRecormon®

Study groups in NCT01015352
Study groupRoleWhat they receive
Arm AActive comparatorAzacitidine 75mg/sqm SQ per day for 5 days every 28 days for 6 courses and 12 additional maintenance courses in responders.
Receives: Drug: Azacitidine
Arm BActive comparatorAzacitidine: 75mg/sqm SQ per day for 5 days every 28 days for 6 courses AND Epoetin beta : 60000U weekly SQ injections (to be adapted according to Hb as described above) 12 additional maintenance courses are planned in responders
Receives: Drug: Azacitidine; Drug: Epoetin beta

What is being measured

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

  1. To determine the major erythroid response rate after 6 courses, assessed according to IWG 2000 criteria

    Measured: after 6 courses of treatment in the respective treatment arm

Secondary outcomes (1)

  1. Degree and duration of erythroid response (including red blood cell transfusion independence),overall survival and time to progression and toxicity

    Measured: after 4 and 6 months of treatment until the end of study

Timeline

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

  1. First posted18 Nov 2009 (estimated)
  2. Study startFeb 2009
  3. Primary completionMar 2014
  4. Study completionMar 2014

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
98 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01015352
Sponsor's protocol ID
GFM-Aza-Epo-2008-01
Status last verified
Nov 2009
First submitted
17 Nov 2009
Last updated
19 Mar 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • Thepot S, Ben Abdelali R, Chevret S, Renneville A, Beyne-Rauzy O, Prebet T, Park S, Stamatoullas A, Guerci-Bresler A, Cheze S, Tertian G, Choufi B, Legros L, Bastie JN, Delaunay J, Chaury MP, Sanhes L, Wattel E, Dreyfus F, Vey N, Chermat F, Preudhomme C, Fenaux P, Gardin C; Groupe Francophone des Myelodysplasies (GFM). A randomized phase II trial of azacitidine +/- epoetin-beta in lower-risk myelodysplastic syndromes resistant to erythropoietic stimulating agents. Haematologica. 2016 Aug;101(8):918-25. doi: 10.3324/haematol.2015.140988. Epub 2016 May 26.

    PubMed 27229713

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Azacitidine and Epoetin beta in people with Myelodysplastic Syndromes, run by Groupe Francophone des Myelodysplasies at 29 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 10 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 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

To determine the major erythroid response rate after 6 courses, assessed according to IWG 2000 criteria (time frame: after 6 courses of treatment in the respective treatment arm). 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 NCT01015352, which also lists 1 linked publication.

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 Mar 2014.

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