Clinical Trial Detail

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.

- Ages Eligible for Study: 18 Years and older

- Genders Eligible for Study: Both

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

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

- RAEB-1 (5% - 9% BM blasts)

- RAEB-2 (10% - 20% BM blasts)

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

- RAEB-t (21% - 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 g/dL)

- 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 transplantation

- 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 participate

Other eligibility criteria may apply.

- 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 (ULN)

- 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 immunotherapy

- 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

Other exclusion criteria may apply.