Efficacy and Safety of IV Rigosertib in MDS Patients With Excess Blasts Progressing After Azacitidine or Decitabine

• Status: Completed
• Trial end date: 2017-06-29
• Target enrollment: 0
• Participant gender: All

Summary

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: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Onconova Therapeutics, Inc.
• Treatments: Azacitidine; Decitabine; ON 01910

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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 immunotherapy.

• 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.