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NMDS Group

Sponsor : Nordic MDS group

Principal investigator : Eva Hellström-Lindberg

 

Status : 30 patients enrolled. Closed for inclusion August, 2011.

Start : January 2010

Inclusion criteria :

  • Must be ³18 years of age at the time of signing the informed consent form
  • MDS at IPSS Low or Int-1, or mixed MDS/MPD; either CMML with <10% marrow blasts or RARS-T
  • Patients with high or intermediate probability for response according to the predictive model2 should be refractory to EPO / darbepoetin (equivalent to >60 000 U of EPO / week for >8 weeks) followed by EPO + G-CSF for >8 weeks, or biosimilar drugs in equipotent doses, or EPO + G-CSF upfront for 8 weeks.
  • Patients with low probability for response according to the predictive model, could be included without prior EPO/G-CSF treatment
  • Transfusion need >4 units over the last 8 weeks, or >8 units over the last 26 weeks.
  • Subject has signed the informed consent document.
  • Men and women of childbearing potential must use effective contraception during, and for up to 3 months after treatment.

Exclusion criteria :

  • Pregnant or lactating females.
  • Patients who are eligible for curative treatment
  • Expected survival less than 24 weeks.
  • Symptomatic thrombocytopenia / active bleeding
  • Patients with JAK-2 positive RARS-T if eligible for new investigational drugs
  • Serum biochemical values as follows: 

  1.  Serum creatinine >2.0 mg/dL (177 micromol/L)
  2.  Serum aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase(SGPT) >3.0 x upper limit of normal (ULN)
  3.  Serum total bilirubin >1.5 mg/dL (26 micromol/L)

  • Uncontrolled systemic infection
  • Considered not capable of following the study protocol

Primary endpoint : number of patients reaching transfusion independency

Treatment : Azacitidine 75mg/m(2) for 6 cycles. Another 2 cycles with the addition of EPO for those not responding to the first 6 cycles.

Report: Abstract EHA Tobiasson, M et al; "Evaluation of Azacitidine in transfusion-dependent, Epo-refractory patients with lower-risk MDS."

Article: Mutations in histone modulators are associated with prolonged survival during azacitidine therapy.
Tobiasson M, McLornan DP, Karimi M, Dimitriou M, Jansson M, Azenkoud AB, Jädersten M, Lindberg G, Abdulkadir H, Kulasekararaj A, Ungerstedt J, Lennartsson A, Ekwall K, Mufti GJ, Hellström-Lindberg E. Oncotarget. 2016; http://www.ncbi.nlm.nih.gov/pubmed/26959885.