A Study of Combined Deferasirox, Vitamin D and Azacytidine in High Risk MDS

NCT01718366 | Unknown Phase 1 DMC

• 1 other identifier: GFM-EXVD-AZA-2011-005623-41
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 15

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D and Azacitidine Patients will be received 6 cycles of treatment (except if progression, unacceptable toxicity or withdrawn of patients occured) After 3 and 6 cycles, an evaluation will be done to evaluate the efficacy of the treatment.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

Conditions

MDS

Outcome Measures

Primary Outcomes (1)

• 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

  6 month of treatment

Study Arms (2)

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

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

Drug: Deferasirox, Vitamin D and Azacitidine

Interventions

Deferasirox, Vitamin D and Azacitidine DRUG

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)

Also known as: Exjade, VitaminD, Vidaza

ferritin level > 1000ng/ml; ferritin level >300ng/ml and < 1000ng/ml

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Groupe Francophone des Myelodysplasies: lead
• Novartis: collaborator

Study Sites (15)

GENT

Ghent, 9000, Belgium

Location

Centre Hospitalier de La Cote Basque

Bayonne, 64100, France

Location

Hôpital Avicenne

Bobigny, 93009, France

Location

Centre Hospitalier de Boulogne sur Mer

Boulogne-sur-Mer, France

Location

CHU Le Mans

Le Mans, France

Location

Hôpital Saint Vincent de Paul

Lille, 59020, France

Location

CHU Limoges

Limoges, 87042, France

Location

CHU Brabois

Nancy, 54511, France

Location

CHU Nantes

Nantes, 44093, France

Location

Centre Catherine de Sienne

Nantes, France

Location

Hôpital saint Louis

Paris, 75010, France

Location

Hôpital cochin

Paris, 75679, France

Location

Hôpital Necker

Paris, 75743, France

Location

CHU Poitiers

Poitiers, 86021, France

Location

IUCT Oncopole Toulouse

Toulouse, France

Location

MeSH Terms

Interventions

Deferasirox; Vitamin D; Azacitidine

Intervention Hierarchy (Ancestors)

Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Olivier Hermine, MD

  Necker Hospital (Paris)

  PRINCIPAL INVESTIGATOR

• Pierre Fenaux, MD

  Saint Louis Hospital (Paris)

  STUDY DIRECTOR

• Felipe Suarez, MD

  Necker Hospital (Paris)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2012
• First Posted: October 31, 2012
• Study Start: February 1, 2013
• Primary Completion: February 1, 2019
• Study Completion: February 1, 2019
• Last Updated: January 10, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (14); BE (1)