A study to assess the efficacy and safety of rigosertib given by continuous intravenous infusion for 72 hours in patients with a blood disease called myelodysplastic syndrome who have failed azacitidine or decitabine treatments

Phase 1

• Conditions: Myelodysplastic Syndrome; MedDRA version: 14.1Level: PTClassification code 10028533Term: Myelodysplastic syndromeSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-001124-19-IT
• Lead Sponsor: Onconova Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-07-10
• Last Update Posted: 7 January 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

a. =18 years of age;
b. Diagnosis of MDS confirmed within 6 weeks prior to Screening according to WHO criteria or FAB classification;
c. 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 x 10e9/L at study entry
- Stable WBC at least 4 weeks prior to Screening and not requiring intervention for WBC control with hydroxyurea, chemotherapy, or leukophoresis;
d. At least one cytopenia (ANC < 1800/µL or PLT count < 100,000/µL or hemoglobin [Hgb] < 10 g/dL);
e. Progression (according to 2006 IWG criteria) at any time after initiation of subcutaneous or intravenous AZA or DEC 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
- 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.
f. Has failed to respond to, relapsed following, not eligible, or opted not to participate in BM transplantation;
g. Off all other treatments for MDS for at least 4 weeks, except for AZA or DEC. Filgrastim (G-CSF) and EPO are allowed before and during the study as clinically indicated;
h. No medical need for induction chemotherapy;
i. ECOG performance status of 0, 1 or 2;
j. Willing to adhere to the prohibitions and restrictions specified in this protocol;
k. Patient must sign an informed consent form (ICF) indicating that s/he understands the purpose of and procedures required for the study and is willing to participate
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 45

Exclusion Criteria

a. Previous participation in a clinical study of IV or oral rigosertib;
b. Anemia due to factors other than MDS (including hemolysis or gastrointestinal [GI] bleeding) unless stabilized for 1 week after RBC transfusion;
c. Any active malignancy within the past year, except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast;
d. Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia;
e. Active infection not adequately responding to appropriate therapy;
f. Total bilirubin = 1.5 mg/dL not related to hemolysis or Gilbert’s disease;
g. ALT/AST = 2.5 x upper limit of normal (ULN);
h. Serum creatinine = 2.0 mg/dL;
i. Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of < 130 mEq/L);
j. Female patients who are pregnant or lactating;
k. Patients who are unwilling to follow strict contraception requirements (including 2 reliable methods in combination: one non-hormonal, highly-reliable method [diaphragm, condoms with spermicidal foam or jelly, or sterilization] plus one additional reliable method [birth control pills, intrauterine device, contraceptive injections, or contraceptive patches]) before entry and throughout the study, up to and including the 30-day nontreatment follow-up period;
l. Female patients with reproductive potential who do not have a negative urine beta-human chorionic gonadotropin (ßHCG) pregnancy test at Screening;
m. Major surgery without full recovery or major surgery within 3 weeks of Baseline/Cycle 1 Day 1 (C1D1) visit;
n. Uncontrolled hypertension (defined as a systolic pressure =160 mmHg and/or a diastolic pressure = 110 mmHg);
o. New onset seizures (within 3 months prior to Baseline/C1D1) or poorly controlled seizures;
p. Any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy;
q. Prior treatment with low-dose cytarabine during the past 2 years;
r. Investigational therapy within 4 weeks of Baseline/C1D1 visit;
s. Psychiatric illness or social situation that would limit the patient’s ability to tolerate and/or comply with study requirements.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified