MDSPhase 1/2GFM-EXVD-AZANCT01718366
A Study of Combined Deferasirox, Vitamin D and Azacytidine in High Risk MDS
A Phase 1/2 study testing Deferasirox, Vitamin D and Azacitidine in people with MDS, run by Groupe Francophone des Myelodysplasies at 15 sites in 2 countries.
Trial summary
Determinate safety and response rate of the association Deferasirox -Vitamine D - Azacitidine in treatment of high risk MDS Deferasirox Exjade: The dose of Deferasirox will be assigned according to the ferritin level. Dose escalation is scheduled during the phase I, with 5 additional patients per group. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- MDS
- What is being tested?
- Deferasirox, Vitamin D and Azacitidine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 15 sitesin 2 countries
- Study dates
- Feb 2013to Feb 2019
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- High risk MDS, according to OMS classification
- High risk CMML (WBC < 13 G/L)
- AREBT of the FAB classification with less than 30% of blastes
- IPSS>=1.5 (int-2 and high risk)
- Age >=18y
- Performance status<=2 (ECOG)
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- Bilirubin and transaminase < 1.5 x ULN
- Normal renal function
- Patient not eligible for Allogeneic stem cell transplant
- Male and female patients must use an effective contraceptive method during the study and for a minimum of 3 months after study treatment.
- Agree the need for the use of a condom if engaged in sexual activity with a pregnant woman or a woman of childbearing potential. during the entire period of treatment, even if disruption of treatment and during 3 months after end of treatment
- Male patient: Agree not to conceive during treatment and study drug therapy (including doses interruptions) and for 3 months after the end of the study drug therapy
- Agree not to donate semen during study drug therapy and for one week after end of study drug therapy.
- Agree to learn about the procedures for preservation of sperm,before starting treatment
- Patient be able to adhere to the study visit schedule and other protocol requirements
Who cannot join
- Active infection or uncontrolled disease
- Use of cytotoxic chemotherapeutic agents or experimental agents(agents that are not commercially available) for the treatment of MDS within 28 days. In case of used of cytotoxic chemotherapeutic agents or hypomethylating agent a wash out of 3 mont is required.
- Active Cancer or Cancer within one year before inclusion
- Previous calcic urinary lithiasis
- Previous hyperparathyroid primitive disease or uncontrolled
- Hypercalcemia, hyperphosphoremia, hypervitaminosis D
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- Patient already include in another experimental study
- Active infection by HIV, hepatite B or C
- Pregnant or lactating females
- Patient not able (medical/psychiatric) to understand and sign the written consent
- Patients with a ferritin level less than 300ng/ml
- Patient eligible for an Allogeneic stem cell transplant
Trial locations and contacts
15 sites in 2 countries.
15 sites in 2 countries
France14 sites
Centre Hospitalier de La Cote Basque
Bayonne, 64100
Hôpital Avicenne
Bobigny, 93009
Centre Hospitalier de Boulogne sur Mer
Boulogne-sur-Mer
CHU Le Mans
Le Mans
Hôpital Saint Vincent de Paul
Lille, 59020
CHU Limoges
Limoges, 87042
CHU Brabois
Nancy, 54511
CHU Nantes
Nantes, 44093
Centre Catherine de Sienne
Nantes
Hôpital saint Louis
Paris, 75010
Hôpital cochin
Paris, 75679
Hôpital Necker
Paris, 75743
CHU Poitiers
Poitiers, 86021
IUCT Oncopole Toulouse
Toulouse
About this study
Official title: Phase I-II Study of Association of Deferasirox, Vitamin D and Azacytidine as Treatment of High Risk MDS (IPSS Int-2 and High)
Determinate safety and response rate of the association Deferasirox -Vitamine D - Azacitidine in treatment of high risk MDS
Deferasirox Exjade:
Read more
The dose of Deferasirox will be assigned according to the ferritin level. Dose escalation is scheduled during the phase I, with 5 additional patients per group.
The maximal tolerated dose of Deferasirox will be required for the phase II of the study.
The first dose will be assigned according to the ferritin level of the patient at time of inclusion:
5 mg/kg/d if the ferritin is >300ng/ml and < 1000ng/ml in Group 1 10 mg/kg/d if the ferritin is ≥1000ng/ml) in Group 2
Group 1 : Ferritin 300 to 1000ng /ml:
- cohort 1 : 5 mg/kg/d
- cohort 2 : 10mg/kg/d
- cohort 3 : 15 mg/kg/d
Group 2 : Ferritin > 1000ng /ml:
- cohort 1 : 10 mg/kg/d
- cohort 2 : 15mg/kg/d
- cohort 3 : 20 mg/kg/d 5 patients will be treated by cohort. In absence of toxicity (extra-hematological toxicity grade 3 or 4 or hematological grade 4), 5 additional patients will be included in the next cohort.
Deferasirox will be administrated once daily during all the study period. Uvedose will be administrated once weekly during all the study period (100.000 UI P.O).
Azacitidine will be administrated sc at 75 mg/m²/d, during 7 days, J1 to J7 of each cycles(One cycle is 28 days)
During phase I and II, Deferasirox will always be associated with Vitamin D and Azacitidine
Patients will be received 6 cycles of treatment (except if progression, unacceptable toxicity or withdrawn of patients occured) After 3 and 6 cycles, an evaluation will be done to evaluate the efficacy of the treatment.
No dose modification of deferasirox will be done after 3 cycles of treatment except in case of progression). After 6 cycles, patients with CR, PR, marrow CR or HI will be treated with the same dose of Deferasirox until progression .
Read the detailed description
Deferasirox will be administrated once daily in the morning on an empty stomach, 30 minutes before meal.
Deferasirox will be stopped if the ferritin level is under 100 ng/ml,and could be restarted is the ferritin level increase to 200 ng/ml
Uvedose dose could be adjusted according to the phosphocalcic metabolism parameters and the plasma Vitamin D3 level.
- Conditions
- MDS
- Being tested
- Deferasirox, Vitamin D and Azacitidine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Deferasirox, Vitamin D and AzacitidineDrug
Also called Exjade, VitaminD, Vidaza
association of Deferasirox (group 1: 5-10-15/mg/kg/day according to dose level group), Vitamine D (100000U/week) and Azacitidine (75 mg/kg/day day1-day7)
| Study group | Role | What they receive |
|---|---|---|
| ferritin level >300ng/ml and < 1000ng/ml | Experimental | Patients will be included in 2 groups according to the ferritin level at time of inclusion.
Patients with the ferritin level >300ng/ml and < 1000ng/ml, will be included in Group 1.
Interventions: Deferasirox, Vitamin D (100000/week) and Azacitidine (75 mg/kg/day Day1 today 7)
5 patients in each cohort: Cohort 1: Deferasirox: 5mg/kg/d Cohort 2: Deferasirox: 10mg/kg/d Cohort 3: Deferasirox: 15mg/kg/d Receives: Drug: Deferasirox, Vitamin D and Azacitidine |
| ferritin level > 1000ng/ml | Experimental | Patients will be included in 2 groups according to the ferritin level at time of inclusion.
Patients with the ferritin level > 1000ng/ml, will be included in Group 2. Intervention: Deferasirox, Vitamin D (100000/week) and Azacitidine (75 mg/kg/day Day1 today 7)
5 patients in each cohort: Cohort 1: Deferasirox: 10mg/kg/d Cohort 2: Deferasirox: 15mg/kg/d Cohort 3: Deferasirox: 20mg/kg/d Receives: Drug: Deferasirox, Vitamin D and Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximal tolerated dose(MTD
patient will be evaluable after at least one cycle. Treatment will be administrated during 6 month and responders will be treated until progression or death
Measured: 6 month of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2012 (estimated)
- Study startFeb 2013
- Primary completionFeb 2019 (estimated)
- Study completionFeb 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MDSStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Groupe Francophone des Myelodysplasies
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Olivier Hermine, MD, Principal investigator, Necker Hospital (Paris)Pierre Fenaux, MD, Study director, Saint Louis Hospital (Paris)Felipe Suarez, MD, Study chair, Necker Hospital (Paris)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01718366
- Sponsor's protocol ID
- GFM-EXVD-AZA-2011-005623-41
- Acronym
- GFM-EXVD-AZA
- Status last verified
- Jan 2018
- First submitted
- 24 Oct 2012
- Last updated
- 10 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I-II Study of Association of Deferasirox, Vitamin D and Azacytidine as Treatment of High Risk MDS (IPSS Int-2 and High)
- ClinicalTrials.gov ID
- NCT01718366
- Acronym / sponsor ID
- GFM-EXVD-AZA / GFM-EXVD-AZA-2011-005623-41
- Conditions
- MDS
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Groupe Francophone des MyelodysplasiesUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Feb 2013 (actual)
- Primary completion
- Feb 2019 (estimated)
- Study completion
- Feb 2019 (estimated)
- First posted
- 31 Oct 2012 (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.
Determinate safety and response rate of the association Deferasirox -Vitamine D - Azacitidine in treatment of high risk MDS
Deferasirox Exjade:
The dose of Deferasirox will be assigned according to the ferritin level. Dose escalation is scheduled during the phase I, with 5 additional patients per group.
The maximal tolerated dose of Deferasirox will be required for the phase II of the study.
The first dose will be assigned according to the ferritin level of the patient at time of inclusion:
5 mg/kg/d if the ferritin is >300ng/ml and < 1000ng/ml in Group 1 10 mg/kg/d if the ferritin is ≥1000ng/ml) in Group 2
Group 1 : Ferritin 300 to 1000ng /ml:
- cohort 1 : 5 mg/kg/d
- cohort 2 : 10mg/kg/d
- cohort 3 : 15 mg/kg/d
Group 2 : Ferritin > 1000ng /ml:
- cohort 1 : 10 mg/kg/d
- cohort 2 : 15mg/kg/d
- cohort 3 : 20 mg/kg/d 5 patients will be treated by cohort. In absence of toxicity (extra-hematological toxicity grade 3 or 4 or hematological grade 4), 5 additional patients will be included in the next cohort.
Deferasirox will be administrated once daily during all the study period. Uvedose will be administrated once weekly during all the study period (100.000 UI P.O).
Azacitidine will be administrated sc at 75 mg/m²/d, during 7 days, J1 to J7 of each cycles(One cycle is 28 days)
During phase I and II, Deferasirox will always be associated with Vitamin D and Azacitidine
Patients will be received 6 cycles of treatment (except if progression, unacceptable toxicity or withdrawn of patients occured) After 3 and 6 cycles, an evaluation will be done to evaluate the efficacy of the treatment.
No dose modification of deferasirox will be done after 3 cycles of treatment except in case of progression). After 6 cycles, patients with CR, PR, marrow CR or HI will be treated with the same dose of Deferasirox until progression .
Detailed description
Deferasirox will be administrated once daily in the morning on an empty stomach, 30 minutes before meal.
Deferasirox will be stopped if the ferritin level is under 100 ng/ml,and could be restarted is the ferritin level increase to 200 ng/ml
Uvedose dose could be adjusted according to the phosphocalcic metabolism parameters and the plasma Vitamin D3 level.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ferritin level >300ng/ml and < 1000ng/ml | Experimental | Drug: Deferasirox, Vitamin D and AzacitidinePatients will be included in 2 groups according to the ferritin level at time of inclusion. Patients with the ferritin level >300ng/ml and < 1000ng/ml, will be included in Group 1. Interventions: Deferasirox, Vitamin D (100000/week) and Azacitidine (75 mg/kg/day Day1 today 7) 5 patients in each cohort: Cohort 1: Deferasirox: 5mg/kg/d Cohort 2: Deferasirox: 10mg/kg/d Cohort 3: Deferasirox: 15mg/kg/d |
| ferritin level > 1000ng/ml | Experimental | Drug: Deferasirox, Vitamin D and AzacitidinePatients will be included in 2 groups according to the ferritin level at time of inclusion. Patients with the ferritin level > 1000ng/ml, will be included in Group 2. Intervention: Deferasirox, Vitamin D (100000/week) and Azacitidine (75 mg/kg/day Day1 today 7) 5 patients in each cohort: Cohort 1: Deferasirox: 10mg/kg/d Cohort 2: Deferasirox: 15mg/kg/d Cohort 3: Deferasirox: 20mg/kg/d |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- High risk MDS, according to OMS classification
- High risk CMML (WBC < 13 G/L)
- AREBT of the FAB classification with less than 30% of blastes
- IPSS>=1.5 (int-2 and high risk)
- Age >=18y
Key exclusion criteria (12 listed)
- Active infection or uncontrolled disease
- Use of cytotoxic chemotherapeutic agents or experimental agents(agents that are not commercially available) for the treatment of MDS within 28 days. In case of used of cytotoxic chemotherapeutic agents or hypomethylating agent a wash out of 3 mont is required.
- Active Cancer or Cancer within one year before inclusion
- Previous calcic urinary lithiasis
- Previous hyperparathyroid primitive disease or uncontrolled
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 |
|---|---|---|
| Deferasirox, Vitamin D and AzacitidineAlso: Exjade, VitaminD, Vidazaassociation of Deferasirox (group 1: 5-10-15/mg/kg/day according to dose level group), Vitamine D (100000U/week) and Azacitidine (75 mg/kg/day day1-day7) | Drug | ferritin level > 1000ng/ml, ferritin level >300ng/ml and < 1000ng/ml |
Primary outcome
To determine the maximal tolerated dose(MTD
Time frame: 6 month of treatment
patient will be evaluable after at least one cycle. Treatment will be administrated during 6 month and responders will be treated until progression or death
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2018.
- Individual participant dataSharing planned: No
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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.
Olivier Hermine, MD principal investigator
Necker Hospital (Paris)
Pierre Fenaux, MD study director
Saint Louis Hospital (Paris)
Felipe Suarez, MD study chair
Necker Hospital (Paris)
15 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Deferasirox, Vitamin D and Azacitidine in people with MDS, run by Groupe Francophone des Myelodysplasies at 15 sites in 2 countries.
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 12 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: status not confirmed, as of the sponsor's last update on 10 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in France, Belgium. 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?
Results are not available in the source record.
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 maximal tolerated dose(MTD (time frame: 6 month of treatment). 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 10 Jan 2018.