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

NCT ID: NCT01305135

Last Updated: 2017-06-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

41 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-12-30

Study Completion Date

2016-05-09

Brief Summary

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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

Detailed Description

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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).

Conditions

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High Grade Myelodysplastic Syndrome Lesions

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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)

Group Type EXPERIMENTAL

azacitidine and idarubicin

Intervention Type DRUG

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

Azacitidine 75mg/m²/d + idarubicin 10mg/m²/d

palier 2: Ida 10mg/m²/d (D8)+ Azacitidine 75mg/m²/d (D1-D7)

Group Type EXPERIMENTAL

azacitidine and idarubicin

Intervention Type DRUG

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

Interventions

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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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Groupe Francophone des Myelodysplasies

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lionel ADES, PHD,MD

Role: PRINCIPAL_INVESTIGATOR

GFM: Groupe Francophone des Myélodysplasies

Locations

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CHU de Haut-Lévèque

Pessac, Bordeaux - Pessac, France

Site Status

CHU d'Amiens

Amiens, , France

Site Status

CHU d'Angers

Angers, , France

Site Status

Hôpital de la cote basque

Bayonne, , France

Site Status

Hôpital Avicenne

Bobigny, , France

Site Status

CHRU de Caen - Hôpital Côte de Nacre

Caen, , France

Site Status

CHU Estaing

Clermont-Ferrand, , France

Site Status

CHU Dijon Hôpital d'enfants

Dijon, , France

Site Status

CHU Albert Michallon

Grenoble, , France

Site Status

CH Le Mans

Le Mans, , France

Site Status

CHU de Limoges

Limoges, , France

Site Status

Centre Hospitalier Lyon Sud

Lyon, , France

Site Status

Institut Paoli-Calmette

Marseille, , France

Site Status

CHU Brabois

Nancy, , France

Site Status

CHU Hotel dieu

Nantes, , France

Site Status

CHU NICE, Hôpital l'Archet

Nice, , France

Site Status

Hôpital saint louis - Hématologie Clinique

Paris, , France

Site Status

Hôpital Saint Louis - Hématologie Séniors

Paris, , France

Site Status

Hôpital Saint Antoine

Paris, , France

Site Status

Hôpital cochin

Paris, , France

Site Status

Centre hospitalier Joffre

Perpignan, , France

Site Status

CH de Périgueux

Périgueux, , France

Site Status

CHU de Poitiers

Poitiers, , France

Site Status

Hôpital Pontchaillou

Rennes, , France

Site Status

Centre Henri Becquerel

Rouen, , France

Site Status

Hôpital Hautepierre

Strasbourg, , France

Site Status

Hôpital PURPAN - Hématologie Clinique

Toulouse, , France

Site Status

Hôpital Purpan - Médecine Interne

Toulouse, , France

Site Status

Hôpital Bretonneau

Tours, , France

Site Status

CH de Valence

Valence, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Hôpital Aziza Othmana

Tunis, , Tunisia

Site Status

Countries

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France Tunisia

Other Identifiers

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GFM-AZA-IDA-09

Identifier Type: -

Identifier Source: org_study_id

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