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)

March 18, 2014 updated by: Groupe Francophone des Myelodysplasies

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
98

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Amiens, France, 80054
        • CHU d'Amiens
      • Angers, France, 49033
        • Hôpital Angers
      • Avignon, France, 84000
        • Hôpital Avignon
      • Bayonne, France, 64100
        • Hopital de la cote Basque
      • Bobigny, France, 93009
        • Hopital Avicenne
      • Boulogne Sur Mer, France, 62321
        • Hôpital Boulogne Sur Mer
      • Caen, France, 14033
        • Hôpital Clémenceau
      • Dijon, France, 21034
        • Hôpital Le Bocage
      • Kremlin Bicêtre, France, 94275
        • Hôpital Kremlin Bicêtre
      • Le Chesnay, France, 78157
        • Hôpital Versailles
      • Lille, France, 59020
        • Hopital Saint Vincent
      • Lille, France, 59037
        • Hôpital Huriez
      • Limoges, France, 87046
        • Hôpital Limoges
      • Lyon, France, 69437
        • Hôpital Edouard Herriot
      • Marseille, France, 13273
        • Hôpital Paoli-Calmettes
      • Nancy, France, 54511
        • Hôpital Brabois
      • Nantes, France, 44035
        • Hôpital Hôtel Dieu
      • Nice, France, 06202
        • Hôpital Archet1
      • Orléans, France, 45067
        • Hopital La Source
      • Paris, France, 75679
        • Hôpital Cochin
      • Paris, France, 75475
        • Hôpital Saint Louis
      • Paris, France, 75571
        • Hôpital Saint Antoine
      • Paris, France, 75475
        • Hôpital Lariboisière
      • Perpignan, France, 66046
        • Hôpital Maréchal Joffre
      • Poitiers, France, 86021
        • Hôpital Jean-Bernard
      • Reims, France, 51092
        • Hôpital Reims
      • Rouen, France, 76038
        • Hopital Henri Becquerel
      • Strasbourg, France, 67098
        • Hôpital Hautepierre
      • Toulouse, France, 31059
        • Hopital Purpan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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
  • 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

Exclusion Criteria:

  • 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Arm A
Azacitidine 75mg/sqm SQ per day for 5 days every 28 days for 6 courses and 12 additional maintenance courses in responders.
Drug: Azacitidine
Azacitidine 75mg/sqm SQ per day for 5 days every 28 days
Other Names:
  • Vidaza®
Active Comparator: Arm B

Azacitidine: 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
Drug: Azacitidine
Azacitidine 75mg/sqm SQ per day for 5 days every 28 days
Other Names:
  • Vidaza®
Drug: Epoetin beta

Epoetin beta : 60000U weekly SQ injections

NeoRecormon®

Other Names:
  • Epoetin beta : 60000U weekly SQ injections

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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
after 6 courses of treatment in the respective treatment arm

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Degree and duration of erythroid response (including red blood cell transfusion independence),overall survival and time to progression and toxicity
Time Frame: after 4 and 6 months of treatment until the end of study
after 4 and 6 months of treatment until the end of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Groupe Francophone des Myelodysplasies

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Roche Pharma AG
Celgene Corporation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Simone Boehrer, MD, Groupe Francophone des Myelodysplasies

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 17, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 17, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 18, 2009

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 19, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 18, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GFM-Aza-Epo-2008-01

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.

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