Three Dosing Schedules of Oral Rigosertib in MDS Patients

NCT02075034 | Withdrawn Phase 1

• 1 other identifier: Onconova 09-10
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study will compare the dosing regimen of oral rigosertib, which has been used in other studies of lower risk Myelodysplastic Syndrome (MDS), with 2 new dosing regimens to determine if one of the new regimens gives improved results as measured by disease status, side effects, and analyses of blood and urine samples.

Conditions

Myelodysplastic Syndrome

Keywords

Myelodysplastic syndrome; MDS; Low risk; Intermediate-1 risk; Intermediate-2 risk; International Prognostic Scoring System; IPSS

Outcome Measures

Primary Outcomes (3)

• Micrograms of rigosertib per milliliter of plasma

  Concentration of rigosertib in plasma will be determined by validated high performance liquid chromatography (HPLC) method.

  0, 0.5, 1, 1.5, 2, 4, 6, and 8 hour on Day 1 of Cycle 1 and on Day 1 of Cycle 2.

• Micrograms of rigosertib per milliliter of urine

  Concentration of rigosertib in urine will be determined by a validated high performance liquid chromatography (HPLC) method.

  Cycle 1 Day 1 and Cycle 2 Day 1 in dosing Regimens 1 and 2 and Cycle 1 Day 1 and Cycle 2 Day 21 in dose Regimen 3

• Number of patients with adverse events

  Adverse events will be summarized by worst grade according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0. All AE presentations will summarize treatment-emergent adverse events (TEAEs), defined as AEs with onset on or after first dose, or onset prior to first dose but with worsening severity after first dose.

  Until 30 days after last dose of study drug (up to 52 weeks)

Secondary Outcomes (2)

• Proportion of patients with hematologic improvement (HI)

  24 weeks

• Concentration of biomarkers in urine

  Up to Cycle 2 Day 15 (up to day 36)

Study Arms (3)

560 mg morning/280 mg afternoon

EXPERIMENTAL

Two 280 mg capsules of rigosertib will be taken in the morning and one 280 mg capsule of rigosertib will be taken in the afternoon.

Drug: rigosertib

420 mg morning and afternon

EXPERIMENTAL

One 280 mg capsule and two 70 mg capsules of rigosertib will be taken in the morning and one 280 mg capsule and two 70 mg capsules of rigosertib will be taken in the afternoon.

Drug: rigosertib

280 mg TID

EXPERIMENTAL

One 280 mg capsule of rigosertib will be taken in the morning, one 280 mg capsule of rigosertib will be taken at mid-day, and one 280 mg capsule of rigosertib will be taken in the afternoon.

Drug: rigosertib

Interventions

rigosertib DRUG

Rigosertib will be supplied as soft gel capsules in strengths of 280 mg and 70 mg.

Also known as: ON 01910.Na

280 mg TID; 420 mg morning and afternon; 560 mg morning/280 mg afternoon

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of MDS according to World Health Organization (WHO) criteria or French-American-British (FAB) classification that must be confirmed by bone marrow (BM) aspirate and/or biopsy within 6 weeks prior to Screening.
• MDS classified as Low-risk or Int-1 risk or Int-2 risk according to International Prognostic Scoring System (IPSS) classification; in addition, patients should never have been classified as High-risk since their MDS was diagnosed.
• Transfusion dependency defined by transfusion of at least 4 units of RBC (red blood cells) within 8 weeks before Screening; pre-transfusion Hgb (hemoglobin) values must be ≤ 9 g/dL to be taken into account.
• Refractory to 8- to 12-week course of ESA (erythropoiesis stimulating agent) administered within the past 2 years before enrollment, or erythropoietin (EPO) level ˃ 500 mU/mL and off ESA for at least 8 weeks before Screening.
• Off all other treatments for MDS for at least 2 weeks prior to Screening.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
• Willing to adhere to the prohibitions and restrictions specified in the protocol.
• The patient must signed an informed consent form (ICF).

You may not qualify if:

• Ongoing clinically significant anemia due to factors such as iron, vitamin B12, or folate deficiencies, auto-immune or hereditary hemolysis, or gastrointestinal bleeding.
• Serum ferritin \< 50 ng/mL.
• Hypoplastic MDS (cellularity \< 10%).
• 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.
• Active infection not adequately responding to appropriate therapy.
• Total bilirubin ≥ 2.0 mg/dL not related to hemolysis or Gilbert's disease.
• Alanine transaminase (ALT) or aspartate transaminase (AST) ≥ 2.5 x the upper limit of normal (ULN).
• Serum creatinine ≥ 2.0 mg/dL.
• Ascites requiring active medical management including paracentesis.
• Hyponatremia (defined as serum sodium value of \< 130 mEq/L).
• Female patients of child-bearing potential or male patients with partners of child-bearing potential who are unwilling to follow strict contraception requirements before entry and throughout the study, up to and including the 30-day non-treatment follow-up period.
• Female patients with reproductive potential who do not have a negative blood or urine pregnancy test at Screening or who are lactating.
• Major surgery without full recovery or major surgery within 3 weeks of Screening.
• Uncontrolled hypertension (defined as a systolic pressure ≥ 160 mmHg and/or a diastolic pressure ≥ 110 mmHg).

Sponsors & Collaborators

• Traws Pharma, Inc.: lead

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

Related Publications (1)

• Garcia-Manero G, Fenaux P. Comprehensive Analysis of Safety: Rigosertib in 557 Patients with Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML). Blood Dec 2016, 128 (22) 2011; ASH 2016.

  RESULT

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

ON 01910

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Mark Heaney, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2014
• First Posted: March 3, 2014
• Study Start: May 1, 2014
• Primary Completion: August 1, 2019
• Study Completion: November 1, 2019
• Last Updated: July 1, 2020

Record last verified: 2018-07

Locations

US (1)