Randomized Study of ON 01910.Na in Refractory Myelodysplastic Syndrome Patients With Excess Blasts

Not Recruiting

Trial ID: NCT01241500


The primary objective of this study is to compare overall survival (OS) in patients receiving ON 01910.Na + best supportive care (BSC) to OS of patients receiving BSC in a population of patients with myelodysplastic syndrome (MDS) with excess blasts (5% to 30% bone marrow blasts) who have failed azacitidine or decitabine treatment. This patient population has no available therapy and a short life expectancy (approximately 4 months). The high level of bone marrow activity of ON 01910.Na documented in Phase 1 and 2 studies has the potential to delay substantially the transition of MDS to Acute Myeloid Leukemia(AML), a very significant and severe complication, which shortens survival of these MDS patients.

Official Title

Phase III MultiCenter Randomized Controlled Study to Assess Efficacy and Safety of ON 01910.Na 72-Hr Continuous IV Infusion in MDS Patients With Excess Blasts Relapsing After or Refractory to or Intolerant to Azacitidine or Decitabine

Stanford Investigator(s)

Alice C. Fan
Alice C. Fan

Assistant Professor of Medicine (Oncology) and, by courtesy, of Urology


Inclusion Criteria:

   - MDS diagnosis confirmed within 6 weeks prior to entry according to WHO or FAB

   - MDS classified as follows, according to WHO and FAB classification:

      - RAEB-1 (5% - 9% BM blasts)

      - RAEB-2 (10% - 19% BM blasts)

      - CMML (10% - 20% BM blasts) and WBC < 13,000/μL

      - RAEB-t (20% - 30% BM blasts), with following criteria:

      - o WBC < 25 x 10E9/L at entry

      - o Stable WBC at least 4 weeks prior to entry and not requiring intervention for
      WBC control with hydroxyurea, chemotherapy, or leukopheresis.

   - At least one cytopenia (ANC < 1800/µL or platelet count < 100,000/µL or hemoglobin <10

   - Progression according to 2006 International Working Group (IWG) criteria any time
   after start of azacitidine or decitabine during past 2 years; or failure to achieve
   complete or partial response or hematological improvement (according to 2006 IWG)
   after at least six 4-week cycles of azacitidine or four 6-week cycles of decitabine
   during past 2 years; or relapse after initial complete or partial response or
   hematological improvement (according to 2006 IWG criteria) observed after at least six
   4-week cycles of azacitidine or four 6-week cycles of decitabine during past 2 years;
   or, intolerance to azacitidine or decitabine defined by drug-related ≥Grade 3 liver or
   renal toxicity leading to discontinuation during the past 2 years.

   - Did not respond to, relapsed after, not eligible for, or opted not to do bone marrow

   - Off other MDS treatments for at least 4 weeks; Filgrastim (G-CSF) and erythropoietin
   allowed before and during the study as clinically indicated.

   - No need for induction chemotherapy

   - ECOG status 0, 1 or 2

   - Willing to adhere to protocol prohibitions and restrictions

   - Patient (or a legally authorized representative) must sign informed consent form to
   indicate patient's understanding study's purpose and procedures and willingness to

Exclusion Criteria:

   - Anemia due to factors other than MDS (including hemolysis or gastrointestinal
   bleeding) unless stabilized for 1 week after RBC transfusion.

   - Any active malignancy within the past year, except basal cell or squamous cell skin
   cancer or carcinoma in situ of the cervix or breast

   - Uncontrolled intercurrent illness including, but not limited to, symptomatic
   congestive heart failure, unstable angina pectoris, or cardiac arrhythmia

   - Active infection not adequately responding to appropriate therapy

   - Total bilirubin ≥1.5 mg/dL not related to hemolysis or Gilbert's disease.

   - Alanine transaminase (ALT)/aspartate transaminase (AST) ≥2.5 x upper limit of normal

   - Serum creatinine ≥2.0 mg/dL

   - Ascites requiring active medical management including paracentesis, or hyponatremia
   (defined as serum sodium value of <130 mEq/L)

   - Pregnant or lactating females

   - Patients unwilling to follow strict contraception requirements (including condom use
   for males with sexual partners, and for females: prescription oral contraceptives
   [birth control pills], contraceptive injections, intrauterine device, double-barrier
   method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, or
   surgical sterilization) before entry and throughout the study

   - Females with reproductive potential who do not have a negative urine beta-human
   chorionic gonadotropin pregnancy test at screening

   - Major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na
   treatment start

   - Uncontrolled hypertension (defined as systolic pressure ≥160 mmHg and/or diastolic
   pressure ≥110 mmHg)

   - New onset seizures (within 3 months prior to first dose of ON 01910.Na) or poorly
   controlled seizures

   - Any other concurrent investigational agent or chemotherapy, radiotherapy, or

   - Prior treatment with low-dose cytarabine during past 2 years Investigational therapy
   within 4 weeks of starting ON 01910.Na

   - Psychiatric illness or social situation that limits the patient's ability to tolerate
   and/or comply with study requirements


drug: ON 01910.Na

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Cancer Clinical Trials Office

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