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

Trial Purpose and Description

Trial Purpose

Although researchers do not know what causes MDS, they do know its symptoms and effects. In MDS, although the bone marrow can still make some blood cells, very few of these cells are released into the blood for use in the body. Therefore, patients with MDS often need transfusions of red blood cells for anemia, platelet transfusions for low platelet counts or bleeding, and antibiotics for serious infections that occur because of low white blood cell counts. MDS may cause an accumulation of abnormal cells called blasts, and this puts patients at a high risk of developing leukemia. The purpose of this study is to determine how well a drug called ON 01910.Na works on people with MDS and to study the safety of ON 01910.Na when it is given to people with MDS.

Participation Guidelines

Eligibility Criteria

Inclusion criteria:

Male and female patientswho meet all of the following criteria are eligiblefor enrollment in the trial:

a.   18 years of age;

b.   Diagnosis ofMDS confirmed within 6 weeks prior to study entry according to WHO

criteria or FAB classification

c.   MDS classified as follows, according to WHO criteriaand FAB classification:

•    RAEB-1 (5% to 9% BM blasts)

•    RAEB-2 (10% to 20% BM blasts)

•    CMML (I 0% to 20% BM blasts) and WBC < 13.000/JlL

•    RAEB-t (21% to 30% BM blasts), meeting the followingcriteria:

o    WBC < 25 x 1 09/L at study entry

o    Stable WBC at least 4 weeks prior to study entry and not requiringintervention for WBC controlwith hydroxyurea, chemotherapy, or leukophoresis;

d.   At least one cytopenia(ANC < 1800/J.LLor platelet count< I00,000/ LL or hemoglobin

[Hgb] <10 g/dL);

e.   Progression (according to 2006 IWG criteria) at any time after initiation of azacitidine or decitabinetreatment during the past 2 years;

or

Failure to achieve completeor partial responseor hematological improvement (according to 2006 IWG) after at least six 4-week cycles of azacitidine or four 6-week cycles of decitabine administered during the past 2 years;

or

Relapse after initial complete or partialresponse or hematological improvement (according to 2006 IWG criteria) observed after at leastsix 4-week cyclesof azacitidine or four 6-week cycles of decitabineadministered during the past 2 years;

or

Intolerance to azacitidine or decitabine definedby drug-related Grade 3liver or renal toxicity leading to treatmentdiscontinuation during the past 2 years;

f.    Has failed to respond to, relapsed following, not eligible,or opted not to participate in bone marrow transplantation;

g.   Off all other treatmentsfor MDS for at least 4 weeks.  Filgrastim (G-CSF)and

erythropoietin are allowed before and during the study as clinicallyindicated;

h.   No medical need for induction chemotherapy;

1.   Eastern Cooperative Oncology Group (ECOG) performance status of O, 1 or 2

j.     Willing to adhere to the prohibitions and restrictions specifiedin this protocol;

k.   Patient (or patient's legallyauthorized representative) must signed an informed consent document indicating that the patientunderstands the purposeof and procedures required for the study and is willing to participate in the study.

Exclusion criteria:

Patients with any of the following will not be enrolled in the study:

a.   Anemia due to factors other than MDS (including hemolysisor gastrointestinal [GI]

bleeding) unless stabilized for I weekafter RBC transfusion;

b.  Any active malignancy within the past year, exceptbasal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast;

c.   Uncontrolled intercurrent illnessincluding, but not limited to, symptomatic congestive heart failure, unstable anginapectoris, or cardiacarrhythmia;

d.  Active infection not adequately responding to appropriate therapy;

e.   Total bilirubin 2:1.5 mg/dL not related to hemolysisor Gilbert's disease;

f.    Alanine transaminase (ALT)/aspartate transaminase (AST)2:2.5 x upper limit of normal

(ULN)

g.   Serum creatinine 2:2.0 mg/dL;

h.  Ascites requiring active medicalmanagement including paracentesis, or hyponatremia

(defined as serum sodium value of <130 mEq/L);

1.   Female patients who are pregnant or lactating;

j.     Patientswho are 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;

k.   Female patients with reproductive potential who do not have a negative urine beta-human

chorionic gonadotropin  (J3HCG) pregnancy test at screening;

I.    Major surgery withoutfull recovery or major surgerywithin 3 weeks of ON 0191O.Na treatment start;

m. Uncontrolled hypertension (defined as a systolicpressure 2:160 mmHg and/or a diastolic

pressure 2: II 0 mmHg);

n.  New onset seizures(within 3 monthsprior to the first dose of ON 0191O.Na) or poorly controlled seizures;

o.   Any other concurrent investigational agent or chemotherapy, radiotherapy, or

immunotherapy;

p.   Prior treatment with low-dosecytarabine during the past 2 years;

q.   Investigational therapywithin 4 weeks of startingON 0 I 9 I O.Na;

Dates:

March 2012

Last Updated:

Study HIC#:

1108008919

Clinicaltrials.gov ID: Yale7332836