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

• Status: Completed
• Trial end date: 2015-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

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

Criteria

Inclusion Criteria:

• ≥ 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

Exclusion Criteria:

• 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

• Psychiatric illness/social situations that would limit the patient's ability to tolerate and/or comply with study requirements