Safety and Pharmacokinetic Study of Oral ON 01910.Na in Patients With Myelodysplastic Syndrome

NCT01048619 | Completed Phase 1

• 1 other identifier: 09-01
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

In other clinical studies, ON 01910.Na has been safely given intravenously to Patients with advanced cancers. However, to treat some Patients, it may be better if ON 01910.Na could be given by mouth. This study will determine if it is safe to give ON 01910.Na by mouth, what is the highest dose can be safely given by mouth, and how much of the drug gets from the stomach into the blood stream when it is given by mouth.

Conditions

Myelodysplastic Syndrome

Keywords

Myelodysplastic Syndrome; MDS

Outcome Measures

Primary Outcomes (1)

• Hematologic and non-hematologic toxicities and the maximum tolerated dose (MTD) of orally administered ON 01910.Na given twice a day up to 14 days at doses escalating from 70 mg to 700 mg

  2 years

Secondary Outcomes (2)

• Characterize pharmacokinetics in a fasting state of ON 01910.Na following administration by the oral route.

  2 years

• Determine any food effect on the pharmacokinetics and the absolute bioavailability of ON 01910.Na administered orally.

  2 years

Study Arms (1)

ON 01910.Na

EXPERIMENTAL

The maximum tolerated dose of oral ON 01910.Na administered in a fasting state (defined as no less than 30 min before next meal) twice a day for 14 days will be determined following an adaptive design at doses between 70 and 700mg.

Drug: ON 01910.Na

Interventions

ON 01910.Na DRUG

In Part I, the bioavailability and tolerability of ON 01910.Na as single, oral, escalating doses in a fasting state (defined as no less than 30 min before next meal) is studied. Three patients get 70mg dose the 1st week. In the absence of drug-related grade 2 toxicity or higher, doses will escalate in each patient weekly (wk) to 140mg (wk 2), 280mg (wk 3), 560mg (wk 4) and 700mg (wk 5). At end of Part I all patients will be eligible for Part II. Part II proceeds if drug is measured in plasma and DLT not observed at 70mg dose in Part I. The maximum tolerated dose of oral ON 01910.Na administered in a fasting state (defined as no less than 30 min before next meal) twice a day for 14 days will be determined following an adaptive design at doses between 70 and 700mg.

Also known as: rigosertib

ON 01910.Na

Eligibility Criteria

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

You may qualify if:

• ≥ 18 years of age
• Diagnosis of MDS confirmed within 6 weeks prior to study entry according to the World Health Organization (WHO) Criteria (see Attachment 1) or the French-American-British (FAB) Classification (see Attachment 2).
• Low, Intermediate 1 or 2 or High Risk MDS according to the IPSS score (see Attachment 3)
• At least one cytopenia (Absolute Neutrophil Count \< 1500/µL or Platelet Count \<100,000/µL or Hemoglobin \<10 g/dL)
• Failure of, or insufficient response to Azacytidine or Decitabine or Lenalidomide or to Erythrocyte Stimulating Agent
• Failed to respond to, relapsed following, or opted not to participate in bone marrow transplantation
• Off all other treatments for MDS (including filgrastim (G-CSF) and erythropoietin) for at least four weeks (only 2 weeks if PROCRITTM is used). Filgrastim (G-CSF) can be used before, during and after the protocol treatment for patients with documented febrile neutropenia (\<500/µl)
• ECOG Performance Status 0, 1 or 2 (see Attachment 4)
• Willing to adhere to the prohibitions and restrictions specified in this protocol
• Patient (or his/her legally authorized representative) must have signed an informed consent document indicating that he/she understands the purpose of and procedures required for the study and is willing to participate in the study

You may not qualify if:

• Anemia due to factors other than MDS (including hemolysis or gastrointestinal bleeding)
• 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
• History of HIV-1 seropositivity
• Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia
• Active infection not adequately responding to appropriate therapy.
• Total bilirubin \> 1.5 mg/dL not related to hemolysis or Gilbert's disease, AST/ALT \> 2 X ULN
• Serum creatinine \> 1.5 x ULN
• Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of \<130 Meq/L).
• Women patients who are pregnant or lactating; Male patients with female sexual partners who are unwilling to follow the strict contraception requirements described in this protocol (see Section 4.4).; Patients who do not agree to use adequate contraceptive \[including prescription oral contraceptives (birth control pills), contraceptive injections, intrauterine device (IUD), double-barrier method (spermicidal jelly or foam with condoms or diaphragm), contraceptive patch, or surgical sterilization\] before entry and throughout the study; Female patients with reproductive potential who do not have a negative serum or urine beta-HCG pregnancy test at screening
• Major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na treatment start.
• Uncontrolled hypertension (defined as a systolic pressure ³ 160 mm Hg and/or a diastolic pressure ³ 110 mm Hg)
• New onset seizures (within 3 months prior to the first dose of ON 01910.Na) or poorly controlled seizures
• Any concurrent investigational agent or chemotherapy, radiotherapy or immunotherapy
• Treatment with standard MDS therapies or investigational therapy within 4 weeks of starting ON 01910.Na

Sponsors & Collaborators

• Traws Pharma, Inc.: lead

Study Sites (2)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Related Publications (2)

• Navada SC, Silverman LR. The safety and efficacy of rigosertib in the treatment of myelodysplastic syndromes. Expert Rev Anticancer Ther. 2016 Aug;16(8):805-10. doi: 10.1080/14737140.2016.1209413. Epub 2016 Jul 15.

  PMID: 27400247 RESULT

• 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

• Rami Komrokji, MD

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

• Azra Raza, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 12, 2010
• First Posted: January 13, 2010
• Study Start: December 1, 2009
• Primary Completion: November 1, 2014
• Study Completion: December 1, 2015
• Last Updated: June 23, 2017

Record last verified: 2017-06

Locations

US (2)