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Efficacy and Safety of IV Rigosertib in MDS Patients With Excess Blasts Progressing After Azacitidine or Decitabine
Trial ID: NCT01928537
This study will examine the effect intravenously administered rigosertib has on the relationship between bone marrow blasts response and overall survival in myelodysplastic syndromes (MDS) patients who have 5-30% bone marrow blasts and who progressed on or after treatment with azacitidine or decitabine.
Phase IIIB, Open-label, Multi-Center Study of the Efficacy and Safety of Rigosertib Administered as 72-hour Continuous Intravenous Infusions in Patients With Myelodysplastic Syndrome With Excess Blasts Progressing On or After Azacitidine or Decitabine
- Diagnosis of MDS confirmed within 6 weeks prior to Screening according to WHO criteria
or French-American-British (FAB) classification.
- MDS classified as follows, according to WHO criteria and FAB classification:
- RAEB-1 (5% to 9% BM blasts)
- RAEB-2 (10% to 19% BM blasts)
- CMML (10% to 20% BM blasts) and white blood cells (WBC) < 13,000/μL
- RAEB-t (20% to 30% BM blasts), meeting the following criteria: WBC < 25,000/μL at
study entry; or, Stable White Blood Cell (WBC) at least 4 weeks prior to
Screening and not requiring intervention for WBC control with hydroxyurea,
chemotherapy, or leukopheresis.
- At least one cytopenia (Absolute Neutrophil Count (ANC) < 1800/μL or Platelet (PLT)
count < 100,000/μL or hemoglobin (Hgb) < 10 g/dL).
- Progression (according to 2006 IWG criteria) at any time after initiation of
subcutaneous or intravenous azacitidine or decitabine treatment per labeling during
the past 2 years, defined as follows:
- For patients with ˂ 5% BMBL, ≥ 50% increase in BMBL to ˃ 5% BMBL
- For patients with 5-10% BMBL, ≥ 50% increase in BMBL to ˃ 10% BMBL
- For patients with 10-20% BMBL, ≥ 50% increase in BMBL to ˃ 20% BMBL
- For patients with 20-30% BMBL, ≥ 50% increase in BMBL to ˃ 30% BMBL
- Any of the following: ≥ 50% decrease from maximum remission/response levels in
granulocytes or PLT; Decrease in Hgb concentration by ≥ 2 g/dL; or, Transfusion
dependence, defined as administration of at least 4 RBC units in the past 8 weeks
before Screening (patients must have Hgb values ˂ 9 g/dL prior to transfusion to
be considered), in the absence of another explanation.
- Has failed to respond to, relapsed following, not eligible, or opted not to
participate in bone marrow transplantation.
- Off all other treatments for MDS for at least 4 weeks, except for azacitidine or
decitabine. Filgrastim (G-CSF) and erythropoietin are allowed before and during the
study as clinically indicated.
- No medical need for induction chemotherapy.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
- Willing to adhere to the prohibitions and restrictions specified in this protocol.
- Patient must signed an informed consent form.
- Previous participation in a clinical study of IV or oral rigosertib.
- Anemia due to factors other than MDS (including hemolysis or gastrointestinal [GI]
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.
- Active infection not adequately responding to appropriate therapy.
- Total bilirubin ≥ 1.5 mg/dL not related to hemolysis or Gilbert's disease.
- ALT/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).
- Female patients who are pregnant or lactating.
- Patients who are unwilling to follow strict contraception requirements.
- Female patients with reproductive potential who do not have a negative urine
beta-human chorionic gonadotropin (βHCG) pregnancy test at Screening.
- Major surgery without full recovery or major surgery within 3 weeks of Baseline/Cycle
1 Day 1 visit.
- Uncontrolled hypertension (defined as a systolic pressure ≥160 mmHg and/or a diastolic
pressure ≥ 110 mmHg).
- New onset seizures (within 3 months prior to Baseline) or poorly controlled seizures.
- Any other concurrent investigational agent or chemotherapy, radiotherapy, or
- Prior treatment with low-dose cytarabine during the past 2 years.
- Investigational therapy within 4 weeks of Baseline/Day 1 visit.
- Psychiatric illness or social situation that would limit the patient's ability to
tolerate and/or comply with study requirements.
drug: rigosertib sodium
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