Efficacy and Safety of 5-day Dosing of ON 01910.Na in Intermediate-1,-2, or High Risk Myelodysplastic Syndrome (MDS)

• Status: Withdrawn
• Trial end date: 2010-09-01
• Target enrollment: 0
• Participant gender: All

Summary

For MDS patients who have not responded to or have progressed after an initial response to DNA methyltransferase inhibitors (DNMTI) and are not stem cell transplant candidates, therapeutic options are limited. Participation in clinical trials such as this one may be considered. The specific objectives of this trial are to find out which dose of ON 01910.Na can be safety given to MDS patients and then find out if this dose of drug has any beneficial effects on the patients' disease. ON 01910.Na is a new, experimental drug; the reason for doing this trial is based on the anti-cancer activity of ON 01910.Na that has been observed in laboratory experiments and in early clinical trials.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

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

Criteria

Inclusion Criteria:

• Diagnosis of MDS confirmed within 4 weeks prior to study entry according to the World Health Organization (WHO) Criteria or the French-American-British (FAB) Classification.

• IPSS score of at least 0.5 (Intermediate-1, Intermediate-2 or High Risk MDS)

• Failure of, or insufficient response to 5-azacitidine or decitabine administered for 4 to 6 cycles.

• 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 2 weeks, and off standard or investigational MDS therapies for four weeks.

• ECOG Performance Status 0, 1 or 2.

• 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 for female patients of reproductive potential.

• Female patients with reproductive potential must have a negative serum beta-HCG pregnancy test at screening.

• 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, ALT or AST ≥ 2 X ULN.

• Serum creatinine ≥ 1.5 mg/dL or calculated creatinine clearance ≤ 60 ml/min/1.73 m2

• Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of <134 Meq/L).

• Female 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.

• Major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na treatment start.

• Uncontrolled hypertension (defined as a systolic pressure ≥ 160 and/or a diastolic pressure ≥ 110).

• 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 myeloid growth factors or erythropoiesis stimulating agents (ESA) within 2 weeks of starting ON 01910.Na.

• 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.