A Study of Combined Deferasirox, Vitamin D and Azacytidine in High Risk MDS (GFM-EXVD-AZA)

January 9, 2018 updated by: Groupe Francophone des Myelodysplasies

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:

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Patients will be received 6 cycles of treatment (except if progression, unacceptable toxicity or withdrawn of patients occured) After 3 and 6 cycles, an evaluation will be done to evaluate the efficacy of the treatment.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 .

Study Overview

Status

Status

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

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

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 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.
50

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
  • Phase 1

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

  • Belgium
      • Gent, Belgium, 9000
        • Gent
  • France
      • Bayonne, France, 64100
        • Centre Hospitalier de la Cote Basque
      • Bobigny, France, 93009
        • Hôpital Avicenne
      • Boulogne sur Mer, France
        • Centre Hospitalier de Boulogne Sur Mer
      • Le MANS, France
        • CHU Le Mans
      • Lille, France, 59020
        • Hôpital Saint Vincent de Paul
      • Limoges, France, 87042
        • CHU Limoges
      • Nancy, France, 54511
        • CHU Brabois
      • Nantes, France, 44093
        • CHU Nantes
      • Nantes, France
        • Centre Catherine de Sienne
      • Paris, France, 75010
        • Hopital Saint Louis
      • Paris, France, 75679
        • Hopital Cochin
      • Paris, France, 75743
        • Hopital Necker
      • Poitiers, France, 86021
        • CHU Poitiers
      • Toulouse, France
        • IUCT Oncopole Toulouse

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:

  • 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)
  • 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

Exclusion Criteria:

  • 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
  • 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

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: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

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.
EXPERIMENTAL: ferritin level >300ng/ml and < 1000ng/ml

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
Drug: Deferasirox, Vitamin D and Azacitidine
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)
Other Names:
  • Vidaza
  • Exjade
  • VitaminD
EXPERIMENTAL: ferritin level > 1000ng/ml

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
Drug: Deferasirox, Vitamin D and Azacitidine
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)
Other Names:
  • Vidaza
  • Exjade
  • VitaminD

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
Measure Description
Time Frame
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
6 month of treatment

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.
Novartis

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: Olivier Hermine, MD, Necker Hospital (Paris)
  • Study Director: Pierre Fenaux, MD, Saint Louis Hospital (Paris)
  • Study Chair: Felipe Suarez, MD, Necker Hospital (Paris)

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 (ACTUAL)

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, 2013

Primary Completion (ANTICIPATED)

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.
February 1, 2019

Study Completion (ANTICIPATED)

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.
February 1, 2019

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).
October 24, 2012

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.
October 30, 2012

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.
October 31, 2012

Study Record Updates

Last Update Posted (ACTUAL)

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.
January 10, 2018

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.
January 9, 2018

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.
January 1, 2018

More Information

Terms related to this study

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-EXVD-AZA-2011-005623-41

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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