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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by Groupe Francophone des Myelodysplasies
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Groupe Francophone des Myelodysplasies
ClinicalTrials.gov Identifier:
NCT01718366
First received: October 24, 2012
Last updated: March 17, 2014
Last verified: October 2012
  Purpose

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Patients will be received 6 cycles of treatment (except if progression, unacceptable toxicity or withdrawn of patients occured) After 3 and 6 cycles, an evaluation will be done to evaluate the efficacy of the treatment.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 Intervention Phase
MDS
Drug: Deferasirox, Vitamin D and Azacitidine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Groupe Francophone des Myelodysplasies:

Primary Outcome Measures:
  • To determine the maximal tolerated dose(MTD [ Time Frame: 6 month of treatment ] [ Designated as safety issue: Yes ]
    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


Estimated Enrollment: 50
Study Start Date: February 2013
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1

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.

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
Other Names:
  • Exjade
  • Uvedose
  • Vidaza
Experimental: Group 2

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.

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
Other Names:
  • Exjade
  • Uvedose
  • Vidaza

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01718366

Contacts
Contact: Felipe Suarez, MD 033144495286 felipe.suarez@nck.aphp.fr
Contact: Benedicte SAMEY, CRA 033148955590 benedicte.samey@avc.aphp.fr

Locations
France
Centre Hospitalier de La Cote Basque Recruiting
Bayonne, France, 64100
Contact: Anne Banos, MD    033559443832    abanos@ch-cotebasque.fr   
Principal Investigator: Anne Banos, MD         
Hôpital Avicenne Recruiting
Bobigny, France, 93009
Contact: Thorsten Braun, MD    33148957051    thorsten.braun@avc.aphp.fr   
Principal Investigator: Thorsten Braun, MD         
Hôpital Saint Vincent de Paul Not yet recruiting
Lille, France, 59020
Contact: Christian Rose, MD    33320874532    rose.christian@ghicl.net   
Principal Investigator: Christian Rose, MD         
Institut Paoli Calmettes Active, not recruiting
Marseille, France, 13009
CHU Brabois Active, not recruiting
Nancy, France, 54511
CHU Nantes Active, not recruiting
Nantes, France, 44093
Hôpital cochin Recruiting
Paris, France, 75679
Contact: François Dreyfus, MD    33158411996    francois.dreyfus@cch.aphp.fr   
Principal Investigator: François Dreyfus, MD         
Hôpital Necker Recruiting
Paris, France, 75743
Contact: Olivier Hermine, MD    33144495283    olivier.hermine@nck.aphp.fr   
Principal Investigator: Olivier Hermine, MD         
Sub-Investigator: Felipe Suarez, MD         
Hôpital saint Louis Recruiting
Paris, France, 75010
Contact: Pierre Fenaux, MD    033170207022    pierre.fenaux@sls.aphp.fr   
Principal Investigator: Pierre Fenaux, MD         
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)
  More Information

No publications provided

Responsible Party: Groupe Francophone des Myelodysplasies
ClinicalTrials.gov Identifier: NCT01718366     History of Changes
Other Study ID Numbers: GFM-EXVD-AZA-2011-005623-41
Study First Received: October 24, 2012
Last Updated: March 17, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

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

ClinicalTrials.gov processed this record on November 25, 2014