Idarubicin Combined to Azacitidine in Int-2 or High Risk Myelodysplastic Syndromes - Full Text View

Purpose

Patients will receive escalating doses of ldarubicine combined to Azacytidine given at the FDA/EMEA approved Schedule and dosing.

For the Phase I study :

Determine the safety and tolerance of escalating doses of Idarubicine combined to Azacitidine in patients with INT-2 or Highr 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 Idarubicine and Azacytidine in patients with INT-2 or Highr risk MDS

Condition	Intervention	Phase
High Grade Myelodysplastic Syndrome Lesions	Drug: azacitine and idarubicine	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Myelodysplastic Syndromes

Drug Information available for: Azacitidine Idarubicin hydrochloride Idarubicin

U.S. FDA Resources

Further study details as provided by Groupe Francophone des Myelodysplasies:

Primary Outcome Measures:

To determined tolerance and dose limiting toxicities to idarubicine and azacitidine association. [ Time Frame: After 12 weeks treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

to determited overall response rate and response duration. [ Time Frame: After six month ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	41
Study Start Date:	December 2010
Estimated Study Completion Date:	January 2015
Estimated Primary Completion Date:	January 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: azacitidine 75mg/m² +idarubicine 5mg/m² phase I : palier 1 have 10 patients and palier 2 have to 10 patients. palier 1: Ida 5mg/m²(D8) + AZACITIDINE 75mg/m²(D1-D7)	Drug: azacitine and idarubicine azacitidine:100mg, 75mg/m², during 7days every 28days. Idarubicine: 5mg/ml, 5mg/m²(palier1)ou 10mg/m²(palier2), 1 day to every cycle to D8
Experimental: Azacitidine 75mg/m² +idarubicine 10mg/m² palier 2: Ida 10mg/m² (D8)+ Azacitidine 75mg/m²(D1-D7)	Drug: azacitine and idarubicine azacitidine:100mg, 75mg/m², during 7days every 28days. Idarubicine: 5mg/ml, 5mg/m²(palier1)ou 10mg/m²(palier2), 1 day to every cycle to D8

Detailed Description:

Patients will receive ldarubicin combined to Azacytidine.

The first 10 patients will receive Idarubicin 5 mg/m2/d on day 8 of each cycle of Azacytidine 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 Azacytidine 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 accoding to the first or second cohort schedule of idarubicin, after review of hematological toxicity and efficacy by an independent safety review committee (SRC).

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 does not indicate cons the use of idarubicin no contra indication to anthracyclines
Age ≥ 18 years
Perfornance Status ≤2 according to ECOG.
Serum creatinine < 1.5 x ULN and normal levels of electrolytes (serum sodium 136-145 nmmol/l, Potassium 3,5-4,5 mmol/l, alkaline Reserve 23-29 mmol/l, , Calcium 2,15-2,5 mmol/l, Phospohore 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01305135

Locations

France
Service des maladies du sang	Active, not recruiting
CHU d'Angers, Angers, France, 49033
Service d'hématologie clinique	Recruiting
hopital Avicenne, Bobigny, France, 93009
Contact: LIONEL ADES, PHD 33 1 48 95 7051 lionel.ades@avc.aphp.fr
Service d'Hématologie Clinique	Active, not recruiting
CHRU Clemenceau, Caen, France, 14033
Service d'Hématologie Clinique	Active, not recruiting
CHU Albert Michallon, Grenoble, France, 38043
Service d'Hématologie Clinique	Active, not recruiting
CHU de Limoges, Limoges, France, 87042
Département d'hématologie	Not yet recruiting
Institut Paoli-Calmette, Marseille, France, 13009
Contact: Norbert VEY, PHD,MD 04 91 22 37 54 veyn@marseille.fnclcc.fr
Principal Investigator: Norbert VEY, PHD,MD
Service d'Hématologie Clinique	Active, not recruiting
CHU NICE, Hôptal l'Archet, Nice, France, 06202
Service d'Hématologie Clinique	Active, not recruiting
Hôpital HOTEL-DIEU, Paris, France, 75181
Département d'hématologie	Active, not recruiting
Centre Henri Becquerel, Rouen, France, 76038
Service d'Hématologie Clinique	Active, not recruiting
Hôpital PURPAN, Toulouse, France, 31059
Centre Hospitalier Lyon Sud	Active, not recruiting
Lyon, France, 69495

Sponsors and Collaborators

Groupe Francophone des Myelodysplasies

Investigators

Principal Investigator:

Lionel ADES, PHD,MD

GFM: Groupe Francophone des Myélodysplasies

More Information

No publications provided

Responsible Party:	Groupe Francophone des Myelodysplasies
ClinicalTrials.gov Identifier:	NCT01305135 History of Changes
Other Study ID Numbers:	GFM-AZA-IDA-09
Study First Received:	February 25, 2011
Last Updated:	March 15, 2013
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Groupe Francophone des Myelodysplasies:

myelodysplastic syndrome, azacitidine, idarubicine

Additional relevant MeSH terms:

Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Azacitidine
Idarubicin

Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on May 22, 2013