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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Groupe Francophone des Myelodysplasies
ClinicalTrials.gov Identifier:
NCT01305135
First received: February 25, 2011
Last updated: March 14, 2014
Last verified: March 2013
  Purpose

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


Condition Intervention Phase
High Grade Myelodysplastic Syndrome Lesions
Drug: azacitidine and idarubicin
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:


Further study details as provided by Groupe Francophone des Myelodysplasies:

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

Secondary Outcome Measures:
  • to determined overall response rate and response duration [ Time Frame: After six months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 41
Study Start Date: December 2010
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: azacitidine 75mg/m²/d + idarubicin 5mg/m²/d

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)

Drug: azacitidine and idarubicin
azacitidine:100mg, 75mg/m²/d, during 7days every 28 days (D1-D7). Idarubicin: 5mg/ml, 5mg/m²/d (palier1) or 10mg/m²/d (palier2), D8
Experimental: Azacitidine 75mg/m²/d + idarubicin 10mg/m²/d
palier 2: Ida 10mg/m²/d (D8)+ Azacitidine 75mg/m²/d (D1-D7)
Drug: azacitidine and idarubicin
azacitidine:100mg, 75mg/m²/d, during 7days every 28 days (D1-D7). Idarubicin: 5mg/ml, 5mg/m²/d (palier1) or 10mg/m²/d (palier2), D8

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

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

Locations
France
Service des maladies du sang
CHU d'Angers, Angers, France, 49033
Service d'Hématologie Clinique
CHRU Clemenceau, Caen, France, 14033
Service d'Hématologie Clinique
CHU Albert Michallon, Grenoble, France, 38043
Service d'Hématologie Clinique
CHU de Limoges, Limoges, France, 87042
Département d'hématologie
Institut Paoli-Calmette, Marseille, France, 13009
Service d'Hématologie Clinique
CHU NICE, Hôpital l'Archet, Nice, France, 06202
Département d'hématologie
Centre Henri Becquerel, Rouen, France, 76038
Service d'Hématologie Clinique
Hôpital PURPAN, Toulouse, France, 31059
CHU d'Amiens
Amiens, France, 80054
CHU d'Angers
Angers, France, 49033
Hôpital de la cote basque
Bayonne, France, 64100
Hôpital Avicenne
Bobigny, France, 93009
CHU de Haut-Lévèque
Bordeaux Pessac, France, 33604
CHU Estaing
Clermont-Ferrand, France, 63000
CHU Dijon Hôpital d'enfants
Dijon, France, 21000
CH Le Mans
Le Mans, France, 72000
Centre Hospitalier Lyon Sud
Lyon, France, 69495
CHU Brabois
Nancy, France, 54511
CHU Hote dieu
Nantes, France, 44093
Hôpital saint louis
Paris, France, 75010
Hôpital Saint Antoine
Paris, France, 75012
Hôpital cochin
Paris, France, 75014
Centre hospitalier Joffre
Perpignan, France, 66046
CHU de Poitiers
Poitiers, France, 86021
CH de Périgueux
Périgueux, France, 24019
Hôpital Pontchaillou
Rennes, France, 35033
Hôpital Hautepierre
Strasbourg, France, 67098
Hôpital Purpan
Toulouse, France, 31059
Hôpital Bretonneau
Tours, France, 37000
CH de Valence
Valence, France, 26953
Institut Gustave Roussy
Villejuif, France, 94805
Tunisia
Hôpital Aziza Othmana
Tunis, Tunisia
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 14, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Groupe Francophone des Myelodysplasies:
myelodysplastic syndrome, azacitidine, idarubicin

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 April 17, 2014