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

Groupe Francophone des Myelodysplasies

Status and phase

Completed

Phase 2

Phase 1

Conditions

High Grade Myelodysplastic Syndrome Lesions

Treatments

Drug: azacitidine and idarubicin

Study type

Interventional

Funder types

Other

Identifiers

NCT01305135

GFM-AZA-IDA-09

Details and patient eligibility

About

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

Full 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).

Enrollment

41 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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