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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01928537
• Date of registration: 21/08/2013
• Prospective Registration: No
• Primary sponsor: Onconova Therapeutics, Inc.
• Public title: Efficacy and Safety of IV Rigosertib in MDS Patients With Excess Blasts Progressing After Azacitidine or Decitabine
• Scientific title: 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
• Date of first enrolment: August 2013
• Target sample size: 67
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01928537
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Australia, Denmark, France, Germany, Italy, Spain, Sweden, United States

Contacts

• Name: Steven M. Fruchtman, MD
• Affiliation: Onconova Therapeutics, Inc.

Key inclusion & exclusion 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 (ßHCG) 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Refractory Anemia With Excess Blasts

Chronic Myelomonocytic Leukemia

Cytopenia

Myelodysplastic Syndromes

Intervention(s)

Drug: rigosertib sodium

Primary Outcome(s)

Relationship of bone marrow blast response and overall survival. [Time Frame: Up to 2 years.]

Secondary Outcome(s)

Concentration of rigosertib in plasma. [Time Frame: Week 1 and week 3.]

Number of patients with hematological improvement. [Time Frame: Up to 2 years after study enrollment.]

Infections. [Time Frame: Up to 2 years after study enrollment.]

Number of patients who transition to Acute Myeloid Leukemia (AML) [Time Frame: Up to 2 years after study enrollment.]

Number of patients with cytogenetic response. [Time Frame: Up to 2 years after study enrollment.]

Number of patients with overall hematologic response. [Time Frame: Up to 2 years after study enrollment.]

Progression-free survival. [Time Frame: Up to 2 years after study enrollment.]

Quality of Life Questionnaire [Time Frame: Up to 2 years after study enrollment.]

Safety. [Time Frame: Study enrollment until 30 days after patient's last dose of rigosertib up to 2 years.]

Secondary ID(s)

2013-001124-19

Onconova 04-24

Source(s) of Monetary Support

Please refer to primary and secondary sponsors