Idarubicin Combined to Azacitidine in Int-2 or High Risk Myelodysplastic Syndromes
- Conditions
- High Grade Myelodysplastic Syndrome Lesions
- Interventions
- Registration Number
- NCT01305135
- Lead Sponsor
- Groupe Francophone des Myelodysplasies
- Brief Summary
Patients will receive escalating doses of ldarubicin combined to Azacitidine given at the FDA/EMEA approved Schedule and dosing.
For the Phase I study :
Determine the safety and tolerance of escalating doses of Idarubicin combined to Azacitidine in patients with INT-2 or higher risk MDS.
For the phase II study:
Primary: Evaluate rate and duration of response (according to IWG 2006 criteria and IWG 2000 criteria) to the combination of Idarubicin and Azacitidine in patients with INT-2 or higher risk MDS
- Detailed Description
Patients will receive ldarubicin combined to Azacitidine.
* The first 10 patients will receive Idarubicin 5 mg/m2/d on day 8 of each cycle of Azacitidine 75 mg/m2/d CI during 7 days (First Cohort ).
* Progression or not to the next cohort of 10 patients : Idarubicin 10 mgm2/d on day 8 of each cycle of Azacitidine 75 mg/m2/d CI during 7 days (Second cohort of 10 patients), will be decided after completion of the first cohort, after review of hematological toxicity by an independent safety review committee (SRC).
* The next 21 patients will be treated either according to the first or second cohort schedule of Idarubicin, after review of hematological toxicity and efficacy by an independent safety review committee (SRC).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 41
- Documented diagnosis of MDS, or CMML with WBC < 13,000/mm3 that meets IPSS criteria for intermediate-2 or high-risk disease,
- IPSS score ≥1.5
- Myocardial function do not contraindicate the use of idarubicin
- Age ≥ 18 years
- Performance Status ≤2 according to ECOG.
- Serum creatinine < 1.5 x ULN and normal levels of electrolytes (serum sodium 136-145 mmol/l, Potassium 3,5-4,5 mmol/l, alkaline Reserve 23-29 mmol/l, , Calcium 2,15-2,5 mmol/l, Phosphore 0,87-1,45 mmol/l) Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) < 1.5 x upper limit of normal (ULN)
- Serum total bilirubin < 1.5 x ULN.
- Must be able to adhere to the study visit schedule and other protocol requirements
- Signed informed consent.
Female subjects of childbearing potential must:
• Accept effective contraception without interruption throughout the duration of study and up to three months after the end of treatment.
Male subjects must
- Agree to use condoms throughout study drug therapy, during any dose interruption and for one week after cessation of study therapy and up to three months after the final treatment if their partner is of childbearing potential and has no contraception.
- Agree to learn the procedures for preservation of sperm
- Uncontrolled infection
- Prior therapy with anthracycline for MDS.
- Eligible for an allogeneic stem cell transplantation.
- Prior therapy with demethylating agents within the last 3 months
- Prior therapy with Hematopoietic growth factor (ESA or G-CSF) agents or cytotoxic agents (oral chemotherapy, low doses AraC) within the last 30 days.
- Prior history of malignancy other than MDS (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix or breast)
- Pregnant or lactating females
- Known HIV-1 positivity
- Contra-indication to Anthracyclines
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description azacitidine 75mg/m²/d + idarubicin 5mg/m²/d azacitidine and idarubicin phase I : palier 1 have 10 patients and palier 2 have to 10 patients. palier 1: Ida 5mg/m²/d (D8) + AZACITIDINE 75mg/m²/d (D1-D7) Azacitidine 75mg/m²/d + idarubicin 10mg/m²/d azacitidine and idarubicin palier 2: Ida 10mg/m²/d (D8)+ Azacitidine 75mg/m²/d (D1-D7)
- Primary Outcome Measures
Name Time Method To determined tolerance and dose limiting toxicities to idarubicin and azacitidine association. After 12 weeks treatment
- Secondary Outcome Measures
Name Time Method to determined overall response rate and response duration After six months
Trial Locations
- Locations (32)
CHU Dijon Hôpital d'enfants
🇫🇷Dijon, France
CHU Albert Michallon
🇫🇷Grenoble, France
Hôpital Hautepierre
🇫🇷Strasbourg, France
Hôpital PURPAN - Hématologie Clinique
🇫🇷Toulouse, France
Hôpital de la cote basque
🇫🇷Bayonne, France
Centre Hospitalier Lyon Sud
🇫🇷Lyon, France
Hôpital Avicenne
🇫🇷Bobigny, France
CHU de Limoges
🇫🇷Limoges, France
CHU Hotel dieu
🇫🇷Nantes, France
Centre hospitalier Joffre
🇫🇷Perpignan, France
Hôpital Aziza Othmana
🇹🇳Tunis, Tunisia
Hôpital Purpan - Médecine Interne
🇫🇷Toulouse, France
Hôpital Saint Antoine
🇫🇷Paris, France
Hôpital Saint Louis - Hématologie Séniors
🇫🇷Paris, France
CHRU de Caen - Hôpital Côte de Nacre
🇫🇷Caen, France
CHU Estaing
🇫🇷Clermont-Ferrand, France
Hôpital saint louis - Hématologie Clinique
🇫🇷Paris, France
CH Le Mans
🇫🇷Le Mans, France
Institut Paoli-Calmette
🇫🇷Marseille, France
CHU Brabois
🇫🇷Nancy, France
CHU NICE, Hôpital l'Archet
🇫🇷Nice, France
Hôpital cochin
🇫🇷Paris, France
CHU de Poitiers
🇫🇷Poitiers, France
CH de Périgueux
🇫🇷Périgueux, France
Hôpital Pontchaillou
🇫🇷Rennes, France
Centre Henri Becquerel
🇫🇷Rouen, France
Hôpital Bretonneau
🇫🇷Tours, France
CH de Valence
🇫🇷Valence, France
Institut Gustave Roussy
🇫🇷Villejuif, France
CHU de Haut-Lévèque
🇫🇷Pessac, Bordeaux - Pessac, France
CHU d'Amiens
🇫🇷Amiens, France
CHU d'Angers
🇫🇷Angers, France