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Randomized Phase II Trial Seeking the Most Promising Drug Association With Azacitidine- in Higher Risk Myelodysplastic Syndromes

Phase 2
18 Years
Open (Enrolling)

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Trial Information

Randomized Phase II Trial Seeking the Most Promising Drug Association With Azacitidine- in Higher Risk Myelodysplastic Syndromes

The main objective of this phase II randomized trial is to identify, among 3 combinations of
Azacitidine and another drug evaluated simultaneously, the most promising combination(s) for
the treatment of higher risk MDS (IPSS Int-2 and High) compared to Azacitidine alone. The 3
tested drugs in combination with Azacitidine are: Valproic Acid, Lenalidomide and

The aim of this trial is to identify, in a situation where several potentially interesting
drugs tested in combination with AZA exist, the most promising combination(s) based on
efficacy compared to azacitidine alone, based on a two-stage design that allows a formal
efficacy comparison between the K=3 investigational treatment groups and the control group.

Inclusion Criteria:

- age>=18 years

- Must be able to adhere to the study visit schedule and other protocol requirements

- Documented diagnosis of MDS, including AREB-t according to FAB classification or CMML
(with WBC < 13,000/mm3) that meets IPSS criteria for intermediate-2 or high-risk.

- Patients should be willing to use adequate contraceptive methods during all the
duration of the study

Exclusion Criteria:

1. Treatment with AZA or Decitabine in the previous 6 months

2. Previous treatment with any HDAC inhibitor (Sodium valproate, Vorinostat,
depsipeptide ou NSC-630176, MS 275, LAQ-824, PXD-101, LBH589, MGCD0103, CRA024781,
etc). If Sodium Valproate (Depakine®) was used for seizure, a wash-out period of at
least 30 days is required and an appropriate treatment replacement should be

3. Ongoing treatment with corticosteroids exceeding 30mg of prednisone per day. A wash
out period of at least 7 days is required.

4. HIV infection

5. Creatinine > 1.5 ULN

6. Serum AST or ALT > 3.0 x upper limit of normal (ULN)

7. Serum total bilirubin > 1.5 mg/dl (except for unconjugated hyperbilirubinemia due to
Gilbert's disease or secondary to MDS).

8. ≥ grade-2 neuropathy

9. Previous history of Acute myeloblastic leukemia (with marrow blasts>30%)

10. Previous history of allogeneic stem cell transplantation

11. Contra-indication to Anthracyclines: Myocardiopathy, uncontrolled infection, serious
renal or hepatic impairment; associated with yellow fever vaccine

12. Known hypersensitivity to the active substance or to any of the excipients of
Vidaza®, of valproate, of divalproate, of valpromide, of Lenalidomide, of
thalidomide, of idarubicin and/or anthracyclines

13. Patients with a history of severe congestive heart failure, clinically unstable
cardiac or pulmonary disease

14. All hepatitis or known personal or familial severe hepatitis, particularly due to

15. Depression with suicidal tendency

16. Use of MILLEPERTUIS, mefloquine

17. No medical insurance in the French Health system

18. Prior history of malignancy other than MDS (except basal cell or squamous cell
carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been
free of disease for ≥ 3 years.

19. Pregnant or lactating females

20. Eligibility for allogeneic stem cell transplantation

21. very altered general condition , with WHO performance status of 4, or life
expectancy of less than 6 months

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Remission, complete, partial or medullary after 6 cycles

Outcome Description:

Achievement of remission, complete, partial or medullary, according to the IWG 2006 criteria39 (see section 10 below) after 6 cycles

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Pierre Fenaux, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Assistance Publique - Hôpitaux de Paris


France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Study ID:




Start Date:

June 2011

Completion Date:

June 2016

Related Keywords:

  • MDS
  • Myelodysplastic Syndromes
  • Preleukemia