Idarubicin Combined to Azacitidine in Int-2 or High Risk Myelodysplastic Syndromes
Information source: Groupe Francophone des Myelodysplasies
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: High Grade Myelodysplastic Syndrome Lesions
Intervention: azacitidine and idarubicin (Drug)
Phase: Phase 1/Phase 2
Status: Active, not recruiting
Sponsored by: Groupe Francophone des Myelodysplasies Official(s) and/or principal investigator(s): Lionel ADES, PHD,MD, Principal Investigator, Affiliation: GFM: Groupe Francophone des Myélodysplasies
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
Clinical Details
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 design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: To determined tolerance and dose limiting toxicities to idarubicin and azacitidine association.
Secondary outcome: to determined overall response rate and response duration
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
CHU d'Amiens, Amiens 80054, France
CHU d'Angers, Angers 49033, France
Hôpital de la cote basque, Bayonne 64100, France
Hôpital Avicenne, Bobigny 93009, France
CHU de Haut-Lévèque, Bordeaux Pessac 33604, France
CHU Estaing, Clermont-Ferrand 63000, France
CHU Dijon Hôpital d'enfants, Dijon 21000, France
CH Le Mans, Le Mans 72000, France
Centre Hospitalier Lyon Sud, Lyon 69495, France
CHU Brabois, Nancy 54511, France
CHU Hote dieu, Nantes 44093, France
Hôpital cochin, Paris 75014, France
Hôpital Saint Antoine, Paris 75012, France
Hôpital saint louis, Paris 75010, France
Centre hospitalier Joffre, Perpignan 66046, France
CHU de Poitiers, Poitiers 86021, France
CH de Périgueux, Périgueux 24019, France
Hôpital Pontchaillou, Rennes 35033, France
Hôpital Hautepierre, Strasbourg 67098, France
Hôpital Purpan, Toulouse 31059, France
Hôpital Bretonneau, Tours 37000, France
CH de Valence, Valence 26953, France
Institut Gustave Roussy, Villejuif 94805, France
Hôpital Aziza Othmana, Tunis, Tunisia
Service des maladies du sang, CHU d'Angers, Angers 49033, France
Service d'Hématologie Clinique, CHRU Clemenceau, Caen 14033, France
Service d'Hématologie Clinique, CHU Albert Michallon, Grenoble 38043, France
Service d'Hématologie Clinique, CHU de Limoges, Limoges 87042, France
Département d'hématologie, Institut Paoli-Calmette, Marseille 13009, France
Service d'Hématologie Clinique, CHU NICE, Hôpital l'Archet, Nice 06202, France
Département d'hématologie, Centre Henri Becquerel, Rouen 76038, France
Service d'Hématologie Clinique, Hôpital PURPAN, Toulouse 31059, France
Additional Information
Starting date: December 2010
Last updated: April 23, 2015
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