A Study of Combined Deferasirox, Vitamin D and Azacytidine in High Risk MDS (GFM-EXVD-AZA)
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Purpose
Determinate safety and response rate of the association Deferasirox -Vitamine D - Azacitidine in treatment of high risk SMD
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 >500ng/ml and < 1000ng/ml in Group 1 10 mg/kg/d if the ferritin is ≥1000ng/ml) in Group 2
Group 1 : Ferritin 500 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 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Patients will be received 6 cycles of treatment (except if progression, unacceptable toxicity or withdrawn of patients occured) After 3 and 6 cycles, an evaluation will be done to evaluate the efficacy of the treatment.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, patients with CR, PR, marrow CR or HI will be treated with the same dose of Deferasirox until progression .
| Condition | Intervention | Phase |
|---|---|---|
|
SMD |
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) |
- 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: | November 2012 |
| 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 >500ng/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:
|
|
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:
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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 |
Inclusion Criteria:
- High risk SMD, according to OMS classification
- 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 500ng/ml
- Patient eligible for an Allogeneic stem cell transplant
Contacts and Locations| Contact: Felipe Suarez, MD | 0144495286 | felipe.suarez@nck.aphp.fr |
| Contact: Benedicte SAMEY, CRA | 33148955590 | benedicte.samey@avc.aphp.fr |
| France | |
| Hôpital Avicenne | Not yet recruiting |
| Bobigny, France, 93009 | |
| Contact: Pierre Fenaux, MD 33148957050 pierre.fenaux@avc.aphp.fr | |
| Hôpital Saint Vincent de Paull | Not yet recruiting |
| Lille, France, 59020 | |
| Contact: Christian Rose, MD 33320874532 rose.christian@ghicl.net | |
| Institut Paoli Calmettes | Not yet recruiting |
| Marseille, France, 13009 | |
| Contact: Norbert Vey, MD 33491223754 veyn@marseille.fnclcc.fr | |
| Contact: Thomas Prebet, MD 33491223754 prebett@marseille.fnclcc.fr | |
| Hôpital Necker | Not yet recruiting |
| Paris, France, 75743 | |
| Contact: Olivier Hermine, MD 33144495283 olivier.hermine@nck.aphp.fr | |
| Hôpital cochin | Not yet recruiting |
| Paris, France, 75679 | |
| Contact: François Dreyfus, MD 33158411996 francois.dreyfus@cch.aphp.fr | |
| Principal Investigator: | Olivier Hermine, MD | Necker Hospital (Paris) |
| Study Director: | Pierre Fenaux, MD | Avicenne Hospital (Bobigny) |
| 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: | October 30, 2012 |
| Health Authority: | France: Agence Nationale de Sécurité du Médicament et des produits de santé |
Additional relevant MeSH terms:
|
Azacitidine Vitamin D Ergocalciferols Vitamins Deferasirox Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions |
Antineoplastic Agents Therapeutic Uses Enzyme Inhibitors Bone Density Conservation Agents Physiological Effects of Drugs Micronutrients Growth Substances Iron Chelating Agents Chelating Agents |
ClinicalTrials.gov processed this record on June 18, 2013