Clinical trial NCT01305135: Idarubicin Combined to Azacitidine in Int-2 or High Risk Myelodysplastic Syndromes
Official title: A Phase I-II Study of the Efficacy and Safety of Idarubicin Combined to Azacitidine in Int-2 or High Risk Myelodysplastic Syndromes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: High Grade Myelodysplastic Syndrome Lesions
Keywords: myelodysplastic syndrome, azacitidine, idarubicin
Lead sponsor: Groupe Francophone des Myelodysplasies
Sponsor class: OTHER
First posted: 2011-02-28
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: To determined tolerance and dose limiting toxicities to idarubicin and azacitidine association.
timeFrame: After 12 weeks treatment
Secondary outcomes:
measure: to determined overall response rate and response duration
timeFrame: After six months
Other outcomes:
Locations:
city: Pessac
country: France
facility: CHU de Haut-Lévèque
state: Bordeaux - Pessac
city: Amiens
country: France
facility: CHU d'Amiens
city: Angers
country: France
facility: CHU d'Angers
city: Bayonne
country: France
facility: Hôpital de la cote basque
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Caen
country: France
facility: CHRU de Caen - Hôpital Côte de Nacre
city: Clermont-Ferrand
country: France
facility: CHU Estaing
city: Dijon
country: France
facility: CHU Dijon Hôpital d'enfants
city: Grenoble
country: France
facility: CHU Albert Michallon
city: Le Mans
country: France
facility: CH Le Mans
city: Limoges
country: France
facility: CHU de Limoges
city: Lyon
country: France
facility: Centre Hospitalier Lyon Sud
city: Marseille
country: France
facility: Institut Paoli-Calmette
city: Nancy
country: France
facility: CHU Brabois
city: Nantes
country: France
facility: CHU Hotel dieu
city: Nice
country: France
facility: CHU NICE, Hôpital l'Archet
city: Paris
country: France
facility: Hôpital saint louis - Hématologie Clinique
city: Paris
country: France
facility: Hôpital Saint Louis - Hématologie Séniors
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Paris
country: France
facility: Hôpital cochin
city: Perpignan
country: France
facility: Centre hospitalier Joffre
city: Poitiers
country: France
facility: CHU de Poitiers
city: Périgueux
country: France
facility: CH de Périgueux
city: Rennes
country: France
facility: Hôpital Pontchaillou
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Strasbourg
country: France
facility: Hôpital Hautepierre
city: Toulouse
country: France
facility: Hôpital PURPAN - Hématologie Clinique
city: Toulouse
country: France
facility: Hôpital Purpan - Médecine Interne
city: Tours
country: France
facility: Hôpital Bretonneau
city: Valence
country: France
facility: CH de Valence
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Tunis
country: Tunisia
facility: Hôpital Aziza Othmana
Study officials:
affiliation: GFM: Groupe Francophone des Myélodysplasies
name: Lionel ADES, PHD,MD
role: PRINCIPAL_INVESTIGATOR
References: