Myelodysplastic SyndromePhase 1/2NCT01305460
Intensified Azacitidine in High Risk Myelodysplastic Syndrome (MDS)
A Phase 1/2 study testing Azacitidine in people with Myelodysplastic Syndrome, run by Groupe Francophone des Myelodysplasies at 21 sites in France.
Trial summary
A phase I/II study of the efficacy and safety of an intensified schedule of Azacitidine (Vidaza®) in intermediate-2 and high risk MDS patients. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Myelodysplastic Syndrome
- What is being tested?
- Azacitidine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 21 sitesFrance
- Study dates
- 5 Jul 2011to 16 Nov 2015
- Phase
- Phase 1/2
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- MDS defined according to WHO classification (also including RAEB-T according to FAB classification) (see appendix 1) with intermediate-2 or high risk IPSS (see appendix 1).
- Age ≥ 18 years and <75 years.
- Must understand and voluntarily sign an informed consent form.
- Must be able to adhere to the study visit schedule and other protocol requirements.
- Patients must have ECOG performance status (PS) of 0 - 2, and no major comorbidities preventing administration of an intensified regimen of azacitidine.
- Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must :
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- Have a negative serum or urine pregnancy test within 2 weeks prior to beginning treatment on this study. Lactating patients are excluded.
- Agree to use, and to be able to comply with, effective contraception without interruption, 4 weeks before starting study drug throughout the entire duration study drug therapy (including doses interruptions) and for 3 months after the end of the study drug therapy.
- Male patients must :
- Agree the need for the use of a condom if engaged in sexual activity with a woman of childbearing potential during the entire period of treatment, even if disruption of treatment and during 3 months after end of treatment.
- Agree to learn about the procedures for preservation of sperm before starting treatment.
- Creatinine < 1.5 N or estimated clearance of creatinine above 30 ml/min.
- Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) < 3.0 x upper limit of normal (ULN).
- Serum total bilirubin < 1.5 mg/dL. (except for unconjugated hyperbilirubinemia due to Gilbert's disease or secondary to MDS-related dyserythropoiesis).
- Health insurance
Who cannot join
- Patients with a history of myeloproliferative syndrome or CMML.
- Known positive status for human immunodeficiency virus (HIV) or hepatitis B or C.
- Pregnant and lactating patients are excluded because the effects of azacitidine on a fetus or a breast-fed child are unknown.
- Uncontrolled intercurrent illness including, but not limited to uncontrolled infection, symptomatic congestive heart failure (NYHA > II), cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients receiving any other standard or investigational cytotoxic treatment for their hematologic malignancy in the last 8 weeks
- Any medical condition which in the opinion of the investigator places the patient at an unacceptably high risk for toxicities of an intensified regimen of azacitidine.
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- Less than 6 months since prior allogeneic bone marrow transplantation.
- Less than 3 months since prior autologous bone marrow or stem cell transplantation
- Active cancer or prior history of malignancy other than MDS (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been free of disease for ≥ 3 years.
- Prior treatment with azacitidine.
- Known allergy/intolerance to azacitidine or mannitol.
- ECOG > 2.
- Life expectancy of less than 3 months.
Trial locations and contacts
21 sites in 1 country.
21 sites in 1 country
France21 sites
CHU d'Amiens
Amiens, 80054
Centre Hospitalier de La Cote Basque
Bayonne, 64100
Hôpital Avicenne
Bobigny, 93009
Centre henri Mondor
Créteil, 94010
CHU Albert Michallon - Service d'Hématologie Clinique
Grenoble, 38043
Centre Hospitalier du Mans
Le Mans, 72037
Hôpital Huriez
Lille, 59037
Hôpital Paoli Calmettes
Marseille, 13273
Centre Hospitalier de Meaux
Meaux, 77100
CHU Brabois
Nancy, 54511
CHU de nantes
Nantes, 44093
Hôpital l'Archet de Nice
Nice, 06202
Hôpital Cochin
Paris, 75004
Hôpital Saint Louis
Paris, 75010
Hopital Saint Louis - AP-HP, Hematology Dpt
Paris, 75475
CHU de Haut-Lévèque
Pessac, 33604
CHU de Poitiers
Poitiers, 86021
CHRU Annecy Hospital
Pringy, 74374
Hôpital Pontchaillou
Rennes, 35033
Hopital Purpan Service d'Hématologie Clinique
Toulouse, 31059
CH de Valence
Valence, 26953
About this study
Official title: A Phase I/II Study of the Efficacy and Safety of an Intensified Schedule of Azacitidine (Vidaza®) in Intermediate-2 and High Risk MDS Patients
A phase I/II study of the efficacy and safety of an intensified schedule of Azacitidine (Vidaza®) in intermediate-2 and high risk MDS patients.
Read the detailed description
The study is an open-label, multicenter phase I/II study.
Treatment Regimen, Dosage and Duration:
Treatment will consist of azacitidine 75mg/m2/d for 5 days every 14 days for 4 cycles (azacitidine-14, cycles 1-4).
- Patients achieving CR or PR will be then treated with 4 cycles of azacitidine 75mg/m2/d for 5 days administered every 21 days (azacitidine-21, cycles 5 to 8) followed by cycles of azacitidine 75mg/m2/d for 7 days administered every 28 days (azacitidine-28, cycles 9 and beyond), to be continued until progression/relapse or toxicity arises).
- Patients not obtaining CR or PR after the initial 4 cycles of azacitidine-14 will continue to receive azacitidine 75mg/m2/d for 5 days every 14 days for 4 additional cycles (cycles 5 to 8). If they achieve CR, PR or HI after 8 cycles, they will then be treated with azacitidine 75mg/m2/d for 5 days every 21 days (azacitidine-21, cycles 9 to 12) and subsequently cycles of azacitidine 75mg/m2/d for 7 days administered every 28 days (azacitidine-28, cycles 13 and beyond) until progression/relapse or toxicity arises.
- Patients not obtaining CR, PR or HI after 8 cycles of azacitidine-14 will go "off-study".
Number of patients to be included:
The trial will enroll at least 27 patients (phase I of the trial) and a maximum of 81 patients (phase II of the trial). A safety analysis will be performed by an independent DSMB after inclusion of 9, 18 and 27 patients. This safety analysis will focus particularly on the clinical consequences of cytopenias. Moreover, a teleconference will be organized twice monthly between the PI and investigators to share safety observations and take appropriate actions if needed. CRFs will be collected every cycle focusing particularly on the safety of this dose intensified study. All AE and SAE will be reported to the DSMB upon reception.
Primary Endpoint:
-Response rate (including CR and PR) according to IWG 2006 criteria for MDS after 4 and 8 cycles 75mg/m2/d azacitidine administered every 2 weeks.
Secondary Endpoints:
- Safety/toxicity profile of azacitidine administered every 14 days (NCI-CTAE)
- Responses (CR, PR, marrow CR, HI) according to IWG 2006 criteria and their duration
- Overall survival and progression (IPSS/AML) free survival.
Sample Size and Duration of Trial:
The first stage of the trial will include 27 patients. The trial will be terminated if 9 or fewer responses are observed. Otherwise, additional patients will be recruited in the second stage until a total sample size of 81 patients is reached.
Duration of inclusion: 24 months for 81 patients Duration of follow-up: 24 months
- Conditions
- Myelodysplastic Syndrome
- Being tested
- Azacitidine
- 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
Treatment will consist of azacitidine 75mg/m2/d for 5 days every 14 days for 4 cycles.
- Patients achieving CR or PR will be then treated with 4 cycles of azacitidine 75mg/m2/d for 5 days every 21 days followed by cycles of azacitidine 75mg/m2/d for 7 days administered every 28 days (cycles 9 and beyond), to be continued until progression/relapse or toxicity arises.
- Patients not obtaining CR or PR after the initial 4 cycles of azacitidine-14 will continue to receive azacitidine 75mg/m2/d for 5 days every 14 days for 4 additional cycles (cycles 5 to 8). If they achieve CR, PR or HI after 8 cycles, they will then be treated with azacitidine 75mg/m2/d for 5 days every 21 days (cycles 9 to 12) and subsequently cycles of azacitidine 75mg/m2/d for 7 days administered every 28 days (cycles 13 and beyond) until progression/relapse or toxicity arises.
- Patients not obtaining CR, PR or HI after 8 cycles of azacitidine-14 will go "off-study".
| Study group | Role | What they receive |
|---|---|---|
| Azacitidine intensified dose | Experimental | Not described Receives: Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate (including CR and PR) according to IWG 2006 criteria for MDS after 4 and 8 cycles 75mg/m2/d azacitidine administered every 2 weeks.
After 4 courses treatment
Measured: 2 months
Secondary outcomes (3)
Safety/toxicity profile of azacitidine administered every 14 days (NCI-CTAE)
After each course of treatment until end of treatment.
Measured: 1-24 months
Responses (CR, PR, marrow CR, HI) according to IWG 2006 criteria and their duration.
After 4 and 8 courses of treatment.
Measured: 2-4 months
Overall survival and progression (IPSS/AML) free survival.
After 4 course of treatment.
Measured: 2 months and further
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2011 (estimated)
- Study start5 Jul 2011
- Primary completionDec 2011
- Study completion16 Nov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Groupe Francophone des Myelodysplasies
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lionel Adès, MD, Study chair, Groupe Francophone des MyélodysplasiesSimone Boehrer, MD, Principal investigator, Groupe Francophone des Myélodysplasies
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01305460
- Sponsor's protocol ID
- GFM-AZA intensif
- Status last verified
- Dec 2021
- First submitted
- 25 Feb 2011
- Last updated
- 28 Dec 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of the Efficacy and Safety of an Intensified Schedule of Azacitidine (Vidaza®) in Intermediate-2 and High Risk MDS Patients
- ClinicalTrials.gov ID
- NCT01305460
- Acronym / sponsor ID
- GFM-AZA intensif
- Conditions
- Myelodysplastic Syndrome
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Groupe Francophone des MyelodysplasiesUniversity, hospital or other
- Study start
- 5 Jul 2011 (actual)
- Primary completion
- Dec 2011 (actual)
- Study completion
- 16 Nov 2015 (actual)
- First posted
- 28 Feb 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A phase I/II study of the efficacy and safety of an intensified schedule of Azacitidine (Vidaza®) in intermediate-2 and high risk MDS patients.
Detailed description
The study is an open-label, multicenter phase I/II study.
Treatment Regimen, Dosage and Duration:
Treatment will consist of azacitidine 75mg/m2/d for 5 days every 14 days for 4 cycles (azacitidine-14, cycles 1-4).
- Patients achieving CR or PR will be then treated with 4 cycles of azacitidine 75mg/m2/d for 5 days administered every 21 days (azacitidine-21, cycles 5 to 8) followed by cycles of azacitidine 75mg/m2/d for 7 days administered every 28 days (azacitidine-28, cycles 9 and beyond), to be continued until progression/relapse or toxicity arises).
- Patients not obtaining CR or PR after the initial 4 cycles of azacitidine-14 will continue to receive azacitidine 75mg/m2/d for 5 days every 14 days for 4 additional cycles (cycles 5 to 8). If they achieve CR, PR or HI after 8 cycles, they will then be treated with azacitidine 75mg/m2/d for 5 days every 21 days (azacitidine-21, cycles 9 to 12) and subsequently cycles of azacitidine 75mg/m2/d for 7 days administered every 28 days (azacitidine-28, cycles 13 and beyond) until progression/relapse or toxicity arises.
- Patients not obtaining CR, PR or HI after 8 cycles of azacitidine-14 will go "off-study".
Number of patients to be included:
The trial will enroll at least 27 patients (phase I of the trial) and a maximum of 81 patients (phase II of the trial). A safety analysis will be performed by an independent DSMB after inclusion of 9, 18 and 27 patients. This safety analysis will focus particularly on the clinical consequences of cytopenias. Moreover, a teleconference will be organized twice monthly between the PI and investigators to share safety observations and take appropriate actions if needed. CRFs will be collected every cycle focusing particularly on the safety of this dose intensified study. All AE and SAE will be reported to the DSMB upon reception.
Primary Endpoint:
-Response rate (including CR and PR) according to IWG 2006 criteria for MDS after 4 and 8 cycles 75mg/m2/d azacitidine administered every 2 weeks.
Secondary Endpoints:
- Safety/toxicity profile of azacitidine administered every 14 days (NCI-CTAE)
- Responses (CR, PR, marrow CR, HI) according to IWG 2006 criteria and their duration
- Overall survival and progression (IPSS/AML) free survival.
Sample Size and Duration of Trial:
The first stage of the trial will include 27 patients. The trial will be terminated if 9 or fewer responses are observed. Otherwise, additional patients will be recruited in the second stage until a total sample size of 81 patients is reached.
Duration of inclusion: 24 months for 81 patients Duration of follow-up: 24 months
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Azacitidine intensified dose | Experimental | Drug: Azacitidine |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- MDS defined according to WHO classification (also including RAEB-T according to FAB classification) (see appendix 1) with intermediate-2 or high risk IPSS (see appendix 1).
- Age ≥ 18 years and <75 years.
- Must understand and voluntarily sign an informed consent form.
- Must be able to adhere to the study visit schedule and other protocol requirements.
- Patients must have ECOG performance status (PS) of 0 - 2, and no major comorbidities preventing administration of an intensified regimen of azacitidine.
Key exclusion criteria (13 listed)
- Patients with a history of myeloproliferative syndrome or CMML.
- Known positive status for human immunodeficiency virus (HIV) or hepatitis B or C.
- Pregnant and lactating patients are excluded because the effects of azacitidine on a fetus or a breast-fed child are unknown.
- Uncontrolled intercurrent illness including, but not limited to uncontrolled infection, symptomatic congestive heart failure (NYHA > II), cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients receiving any other standard or investigational cytotoxic treatment for their hematologic malignancy in the last 8 weeks
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzacitidineAlso: VidazaTreatment will consist of azacitidine 75mg/m2/d for 5 days every 14 days for 4 cycles. * Patients achieving CR or PR will be then treated with 4 cycles of azacitidine 75mg/m2/d for 5 days every 21 days followed by cycles of azacitidine 75mg/m2/d for 7 days administered every 28 days (cycles 9 and beyond), to be continued until progression/relapse or toxicity arises. * Patients not obtaining CR or PR after the initial 4 cycles of azacitidine-14 will continue to receive azacitidine 75mg/m2/d for 5 days every 14 days for 4 additional cycles (cycles 5 to 8). If they achieve CR, PR or HI after 8 cycles, they will then be treated with azacitidine 75mg/m2/d for 5 days every 21 days (cycles 9 to 12) and subsequently cycles of azacitidine 75mg/m2/d for 7 days administered every 28 days (cycles 13 and beyond) until progression/relapse or toxicity arises. * Patients not obtaining CR, PR or HI after 8 cycles of azacitidine-14 will go "off-study". | Drug | Azacitidine intensified dose |
Primary outcome
Response rate (including CR and PR) according to IWG 2006 criteria for MDS after 4 and 8 cycles 75mg/m2/d azacitidine administered every 2 weeks.
Time frame: 2 months
After 4 courses treatment
3 secondary outcomes
Safety/toxicity profile of azacitidine administered every 14 days (NCI-CTAE)
Time frame: 1-24 months
Responses (CR, PR, marrow CR, HI) according to IWG 2006 criteria and their duration.
Time frame: 2-4 months
Overall survival and progression (IPSS/AML) free survival.
Time frame: 2 months and further
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2021.
- Website of the Groupe Francophone des Myélodysplasies (GFM)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lionel Adès, MD study chair
Groupe Francophone des Myélodysplasies
Simone Boehrer, MD principal investigator
Groupe Francophone des Myélodysplasies
21 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Azacitidine in people with Myelodysplastic Syndrome, run by Groupe Francophone des Myelodysplasies at 21 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 15 inclusion and 13 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 28 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Response rate (including CR and PR) according to IWG 2006 criteria for MDS after 4 and 8 cycles 75mg/m2/d azacitidine administered every 2 weeks. (time frame: 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Dec 2021.