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

February 25, 2011
March 14, 2014
December 2010
January 2015   (final data collection date for primary outcome measure)
To determined tolerance and dose limiting toxicities to idarubicin and azacitidine association. [ Time Frame: After 12 weeks treatment ] [ Designated as safety issue: Yes ]
To determined tolerance and dose limiting toxicities to idarubicine and azacitidine association. [ Time Frame: After 12 weeks treatment ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01305135 on ClinicalTrials.gov Archive Site
to determined overall response rate and response duration [ Time Frame: After six months ] [ Designated as safety issue: Yes ]
to determited overall response rate and response duration. [ Time Frame: After six month ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Idarubicin Combined to Azacitidine in Int-2 or High Risk Myelodysplastic Syndromes
A Phase I-II Study of the Efficacy and Safety of Idarubicin Combined to Azacitidine in Int-2 or High Risk Myelodysplastic Syndromes

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

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).
Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
High Grade Myelodysplastic Syndrome Lesions
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 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)

    Intervention: Drug: azacitidine and idarubicin
  • Experimental: Azacitidine 75mg/m²/d + idarubicin 10mg/m²/d
    palier 2: Ida 10mg/m²/d (D8)+ Azacitidine 75mg/m²/d (D1-D7)
    Intervention: Drug: azacitidine and idarubicin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
41
June 2015
January 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
France,   Tunisia
 
NCT01305135
GFM-AZA-IDA-09
Yes
Groupe Francophone des Myelodysplasies
Groupe Francophone des Myelodysplasies
Not Provided
Principal Investigator: Lionel ADES, PHD,MD GFM: Groupe Francophone des Myélodysplasies
Groupe Francophone des Myelodysplasies
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP