A phase I-II study of the efficacy and safety of Idarubicin combined to Azacitidine in int-2 or high risk myelodysplastic syndromes - GFM- Aza-Ida-09

Phase 1

• Conditions: Myelodysplastic syndromes; MedDRA version: 12.1Level: LLTClassification code 10028533Term: Myelodysplastic syndrome

• Registration Number: EUCTR2009-017178-19-FR
• Lead Sponsor: Groupe Francophone des Myélodysplasies

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-07-15
• Last Update Posted: 5 December 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 56

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.
-Non eligible for an allogeneic stem cell transplantation.
-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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Uncontrolled infection
-Prior therapy with anthracycline for MDS.
-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 clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: For the Phase I study : <br>Determine the safety and tolerance of escalating doses of Idarubicine combined to Azacitidine in patients with INT-2 or Highr risk MDS.<br><br>For the phase II study: <br>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.<br><br>;Secondary Objective: Secondary: <br>- the safety (particularly hematological toxicity) of the combination <br>- duration of response,<br>- progression to AML, <br>- survival.<br>- the rate of hematological improvement<br>;Primary end point(s): For Phase I: tolerance of two dose levels of idarubicin associated with azacitidine. It will be analyzed after 2 cycles, <br><br>For Phase II: number of complete responses (CR) + partial response (PR) + RC marrow by IWG 2006 criteria after 3 and 6 cycles of treatment. <br>