Study of 72-Hour Infusion of ON 01910.Na in Patients With MDS or AML

• Status: Completed
• Trial end date: 2014-02-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of this study is to evaluate the efficacy and safety of ON 01910.Na Concentrate when it is administered as an intravenous continuous infusion (IVCI) over 72 hours once every 2 weeks in a broad population of MDS patients. Rationale for this study is based on the activity observed in another study with ON 01910.Na in patients with refractory anemia with excess blasts (RAEB) 1 and 2 MDS. This study will examine ON 01910.Na in a broader population of MDS and AML patients. This phase I/II study will establish the Maximum Tolerated Dose (MTD) starting with a dose of 800 mg/m2 per day administered over 24 hours for 2 consecutive days as a continuous intravenous infusion, once a week for 3 weeks of a 4-week cycle and examine the efficacy and safety profile at the MTD.

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

Details

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

Criteria

Inclusion Criteria:

• > 18 years

• Diagnosis of MDS or AML via bone marrow aspirate and biopsy performed within 8 weeks prior to study entry according to WHO Criteria and FAB Classification. AML patients must be:

not eligible for standard chemotherapy, including newly diagnosed patients over 70 years; with relapsed or refractory AML; and, with AML secondary to prior cancer chemotherapy or evolving from a myeloproliferative/myelodysplastic syndrome.

• Anemia requiring transfusion support with at least one unit of packed red blood cells per month for greater than or equal to 2 months or Hemoglobin < 10 g/dL OR Thrombocytopenia (platelet count < 100,000/µl) OR Neutropenia (absolute neutrophil count < 1,500/µl)

• Failed to respond to, relapsed following, or opted not to participate in bone marrow transplantation

• Off all other treatments for MDS or AML (including filgrastim (G-CSF) and erythropoietin) for at least four weeks. As an exception, 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

• 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 patient 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 or AML (including hemolysis or gastrointestinal bleeding)

• Proliferative (WBC ≥ 12,000/mm3) chronic myelomonocytic leukemia

• 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).

• 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

• 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

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