Phase I Study of ON 01910.Na in Refractory Leukemia or Myelodysplastic Syndrome (MDS)

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

Summary

This is an open-label, Phase I study to determine the highest amount of the study drug, ON 01910.Na, that can be safety given to patients with high risk myelodysplastic syndromes (MDS) or refractory leukemias. Patients will receive ON 01910.Na (at a starting dose of 650 mg/m2) intravenously by 3-day continuous infusion once every 2 weeks. Successive courses will use longer infusion times and/or higher doses of the drug until toxicity, effectiveness, or ineffectiveness is recognized. In addition, the amount of drug in the blood will be measured, any antitumor activity will be documented, and the biological effect of ON 01910.Na on cell-cycle pathways will be evaluated in peripheral blood mononuclear cells.

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

Details

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

Criteria

Inclusion Criteria:

• Patient must have histologically documented or cytologically confirmed diagnosis of acute myelocytic leukemia refractory to standard induction treatment, or relapsed after standard therapy

• Acute lymphocytic leukemia refractory to induction treatment, or relapsed after effective therapy

• Chronic myelocytic leukemia refractory to imatinib therapy or second line tyrosine kinase inhibition, or relapsed after tyrosine kinase inhibition, in chronic, accelerated, or blastic phase

• Chronic lymphocytic leukemia refractory to standard therapy, or relapsed in second relapse

• A myelodysplastic syndrome (including chronic myelomonocytic leukemia) refractory to a hypomethylating agent

• And a int-2 or high myelodysplastic syndrome relapsed after a hypomethylating agent.

• Patients may not be eligible for, or must have declined, bone marrow transplantation or other chemotherapeutic regimens known to produce consistent remissions.

• There are no hematologic exclusions from treatment.

• Patients with prior radiotherapy are eligible unless leukopenia is ascribed to prior radiation treatment, and then entry to study of ON 01910.Na may be initiated when two successive leukocyte counts are rising.

• ECOG Performance Status of 0, 1, or 2 if patient is in the dose escalation phase or 0 or 1 if patient is in the dose escalation phase.

• Patients may have any hematologic parameters without regard to numbers provided that transfusional support is available and the Investigator stipulates that leukopenia is attributable to disease rather than to prior therapy.

• Total bilirubin ≤ 1.5 mg/dL, unless the patient has active hemolysis, or the elevation is secondary to ineffective erythropoiesis.

• Serum creatinine ≤ 1.5 mg/dL, or a calculated creatinine clearance of ≥ 60 mL/min/1.73 m2.

• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) while in the study. If a woman becomes pregnant or suspects she is pregnant while on study, her treating physician should be informed immediately.

• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Patients who have positive blood cultures until they are afebrile for 3 days on antibiotic therapy which will continue.

• Patients who have leukopenia attributed to prior chemotherapy until two successive leukocyte counts are increasing. Patients with rapidly rising WBC (e.g. >50% increase over the previous day for 3 consecutive days) or WBC > 40 x 109/L.

• Patients who have continuing toxicity other than hematologic from prior therapy until it has resolved to grade 1 or less and will not compromise ON 01910.Na administration.

• Patients who are receiving any other investigational agents or concurrent chemotherapy, radiotherapy, or immunotherapy.

• Patients receiving corticosteroids or colony-stimulating factors may continue on these treatments. These agents will not be introduced if previously not employed.

• Patients with known meningeal infiltration may be included in this clinical trial only if intrathecal therapy and/or radiation has been completed, and cerebrospinal fluid cytology is improved.

• Patients with a history of allergic reactions attributable to compounds of similar chemical or biologic composition to ON 01910.Na.

• Patients should have no major third space fluid accumulation, ascites requiring active medical management including paracentesis, peripheral bilateral edema, or hyponatremia (serum sodium value less than 134 Meq/L).

• Patients with uncontrolled intercurrent illness including, but not limited to uncontrolled ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• Pregnant and nursing women are excluded from this study.

• HIV-positive patients receiving combination anti-retroviral therapy are excluded.