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

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ClinicalTrials.gov Identifier: NCT01718366
Recruitment Status : Active, not recruiting
First Posted : October 31, 2012
Last Update Posted : January 10, 2018
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Groupe Francophone des Myelodysplasies

Brief 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.

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Patients will be received 6 cycles of treatment (except if progression, unacceptable toxicity or withdrawn of patients occured) After 3 and 6 cycles, an evaluation will be done to evaluate the efficacy of the treatment.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


Condition or disease Intervention/treatment Phase
MDS Drug: Deferasirox, Vitamin D and Azacitidine Phase 1 Phase 2

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 : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : February 2013
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : February 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vitamin D
U.S. FDA Resources

Arm Intervention/treatment
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:
  • Exjade
  • VitaminD
  • Vidaza
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:
  • Exjade
  • VitaminD
  • Vidaza



Primary Outcome Measures :
  1. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01718366


Locations
Belgium
GENT
Gent, Belgium, 9000
France
Centre Hospitalier de La Cote Basque
Bayonne, France, 64100
Hôpital Avicenne
Bobigny, France, 93009
Centre Hospitalier de Boulogne sur Mer
Boulogne sur Mer, France
CHU Le Mans
Le MANS, France
Hôpital Saint Vincent de Paul
Lille, France, 59020
CHU Limoges
Limoges, France, 87042
CHU Brabois
Nancy, France, 54511
CHU Nantes
Nantes, France, 44093
Centre Catherine de Sienne
Nantes, France
Hôpital saint Louis
Paris, France, 75010
Hôpital cochin
Paris, France, 75679
Hôpital Necker
Paris, France, 75743
CHU Poitiers
Poitiers, France, 86021
IUCT Oncopole Toulouse
Toulouse, France
Sponsors and Collaborators
Groupe Francophone des Myelodysplasies
Novartis
Investigators
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)

Responsible Party: Groupe Francophone des Myelodysplasies
ClinicalTrials.gov Identifier: NCT01718366     History of Changes
Other Study ID Numbers: GFM-EXVD-AZA-2011-005623-41
First Posted: October 31, 2012    Key Record Dates
Last Update Posted: January 10, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Vitamins
Vitamin D
Ergocalciferols
Azacitidine
Deferasirox
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Iron Chelating Agents
Chelating Agents
Sequestering Agents