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

MDS Clinical Trial

— GFM-EXVD-AZA  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01718366
• Other study ID #: GFM-EXVD-AZA-2011-005623-41
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: October 24, 2012
• Last updated: January 9, 2018
• Start date: February 2013
• Est. completion date: February 2019

Study information

• Verified date: January 2018
• Source: Groupe Francophone des Myelodysplasies
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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Patients will be received 6 cycles of treatment (except if progression, unacceptable toxicity or withdrawn of patients occured) After 3 and 6 cycles, an evaluation will be done to evaluate the efficacy of the treatment.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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: February 2019
• Est. primary completion date: February 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• MDS

Intervention

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)

Locations

Country	Name	City	State
Belgium	GENT	Gent
France	Centre Hospitalier de La Cote Basque	Bayonne
France	Hôpital Avicenne	Bobigny
France	Centre Hospitalier de Boulogne sur Mer	Boulogne sur Mer
France	CHU Le Mans	Le MANS
France	Hôpital Saint Vincent de Paul	Lille
France	CHU Limoges	Limoges
France	CHU Brabois	Nancy
France	Centre Catherine de Sienne	Nantes
France	CHU Nantes	Nantes
France	Hôpital cochin	Paris
France	Hôpital Necker	Paris
France	Hôpital saint Louis	Paris
France	CHU Poitiers	Poitiers
France	IUCT Oncopole Toulouse	Toulouse

Sponsors (2)

Lead Sponsor	Collaborator
Groupe Francophone des Myelodysplasies	Novartis

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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