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

Primary Purpose

High Grade Myelodysplastic Syndrome Lesions

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
azacitidine and idarubicin
Sponsored by
Groupe Francophone des Myelodysplasies
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for High Grade Myelodysplastic Syndrome Lesions focused on measuring myelodysplastic syndrome, azacitidine, idarubicin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • CHU de Haut-Lévèque
  • CHU d'Amiens
  • CHU d'Angers
  • Hôpital de la cote basque
  • Hôpital Avicenne
  • CHRU de Caen - Hôpital Côte de Nacre
  • CHU Estaing
  • CHU Dijon Hôpital d'enfants
  • CHU Albert Michallon
  • CH Le Mans
  • CHU de Limoges
  • Centre Hospitalier Lyon Sud
  • Institut Paoli-Calmette
  • CHU Brabois
  • CHU Hotel dieu
  • CHU NICE, Hôpital l'Archet
  • Hôpital saint louis - Hématologie Clinique
  • Hôpital Saint Louis - Hématologie Séniors
  • Hôpital Saint Antoine
  • Hôpital cochin
  • Centre hospitalier Joffre
  • CHU de Poitiers
  • CH de Périgueux
  • Hôpital Pontchaillou
  • Centre Henri Becquerel
  • Hôpital Hautepierre
  • Hôpital PURPAN - Hématologie Clinique
  • Hôpital Purpan - Médecine Interne
  • Hôpital Bretonneau
  • CH de Valence
  • Institut Gustave Roussy
  • Hôpital Aziza Othmana

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

azacitidine 75mg/m²/d + idarubicin 5mg/m²/d

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

Arm Description

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)

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

Outcomes

Primary Outcome Measures

To determined tolerance and dose limiting toxicities to idarubicin and azacitidine association.

Secondary Outcome Measures

to determined overall response rate and response duration

Full Information

First Posted
February 25, 2011
Last Updated
June 6, 2017
Sponsor
Groupe Francophone des Myelodysplasies
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1. Study Identification

Unique Protocol Identification Number
NCT01305135
Brief Title
Idarubicin Combined to Azacitidine in Int-2 or High Risk Myelodysplastic Syndromes
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 Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
December 30, 2010 (Actual)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
May 9, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Groupe Francophone des Myelodysplasies

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
High Grade Myelodysplastic Syndrome Lesions
Keywords
myelodysplastic syndrome, azacitidine, idarubicin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
azacitidine 75mg/m²/d + idarubicin 5mg/m²/d
Arm Type
Experimental
Arm Description
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)
Arm Title
Azacitidine 75mg/m²/d + idarubicin 10mg/m²/d
Arm Type
Experimental
Arm Description
palier 2: Ida 10mg/m²/d (D8)+ Azacitidine 75mg/m²/d (D1-D7)
Intervention Type
Drug
Intervention Name(s)
azacitidine and idarubicin
Intervention Description
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
Primary Outcome Measure Information:
Title
To determined tolerance and dose limiting toxicities to idarubicin and azacitidine association.
Time Frame
After 12 weeks treatment
Secondary Outcome Measure Information:
Title
to determined overall response rate and response duration
Time Frame
After six months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lionel ADES, PHD,MD
Organizational Affiliation
GFM: Groupe Francophone des Myélodysplasies
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU de Haut-Lévèque
City
Pessac
State/Province
Bordeaux - Pessac
ZIP/Postal Code
33604
Country
France
Facility Name
CHU d'Amiens
City
Amiens
ZIP/Postal Code
80054
Country
France
Facility Name
CHU d'Angers
City
Angers
ZIP/Postal Code
49033
Country
France
Facility Name
Hôpital de la cote basque
City
Bayonne
ZIP/Postal Code
64100
Country
France
Facility Name
Hôpital Avicenne
City
Bobigny
ZIP/Postal Code
93009
Country
France
Facility Name
CHRU de Caen - Hôpital Côte de Nacre
City
Caen
ZIP/Postal Code
14033
Country
France
Facility Name
CHU Estaing
City
Clermont-Ferrand
ZIP/Postal Code
63000
Country
France
Facility Name
CHU Dijon Hôpital d'enfants
City
Dijon
ZIP/Postal Code
21000
Country
France
Facility Name
CHU Albert Michallon
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
CH Le Mans
City
Le Mans
ZIP/Postal Code
72000
Country
France
Facility Name
CHU de Limoges
City
Limoges
ZIP/Postal Code
87042
Country
France
Facility Name
Centre Hospitalier Lyon Sud
City
Lyon
ZIP/Postal Code
69495
Country
France
Facility Name
Institut Paoli-Calmette
City
Marseille
ZIP/Postal Code
13009
Country
France
Facility Name
CHU Brabois
City
Nancy
ZIP/Postal Code
54511
Country
France
Facility Name
CHU Hotel dieu
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
CHU NICE, Hôpital l'Archet
City
Nice
ZIP/Postal Code
06202
Country
France
Facility Name
Hôpital saint louis - Hématologie Clinique
City
Paris
ZIP/Postal Code
75010
Country
France
Facility Name
Hôpital Saint Louis - Hématologie Séniors
City
Paris
ZIP/Postal Code
75010
Country
France
Facility Name
Hôpital Saint Antoine
City
Paris
ZIP/Postal Code
75012
Country
France
Facility Name
Hôpital cochin
City
Paris
ZIP/Postal Code
75014
Country
France
Facility Name
Centre hospitalier Joffre
City
Perpignan
ZIP/Postal Code
66046
Country
France
Facility Name
CHU de Poitiers
City
Poitiers
ZIP/Postal Code
86021
Country
France
Facility Name
CH de Périgueux
City
Périgueux
ZIP/Postal Code
24019
Country
France
Facility Name
Hôpital Pontchaillou
City
Rennes
ZIP/Postal Code
35033
Country
France
Facility Name
Centre Henri Becquerel
City
Rouen
ZIP/Postal Code
76038
Country
France
Facility Name
Hôpital Hautepierre
City
Strasbourg
ZIP/Postal Code
67098
Country
France
Facility Name
Hôpital PURPAN - Hématologie Clinique
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Hôpital Purpan - Médecine Interne
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Hôpital Bretonneau
City
Tours
ZIP/Postal Code
37000
Country
France
Facility Name
CH de Valence
City
Valence
ZIP/Postal Code
26953
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Facility Name
Hôpital Aziza Othmana
City
Tunis
Country
Tunisia

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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