Myelofibrosis
Conditions
Brief summary
This is an open-label, one arm, single institution study. Arsenic trioxide \[TrisenoxTM Injection\], 0.25mg/kg/dose administered intravenously over 2 hours. 20 patients Complete remission, partial remission, clinical improvement, progressive disease, stable disease, relapse (per IWG consensus criteria, 2006) Clinical chemistry, hematology and ECGs will be assessed at least weekly during study treatments. Adverse events will be assessed in accordance with the NCI Common Toxicity Criteria, Version 2 at each study visit.
Interventions
DRUGarsenic trioxide
Cytarabine will be administered at a dose of 10 mg/m2 subcutaneously (sc) twice daily (bid) from days 1-14. Triseonx will be administered at a dose of 0.25 mg/kg on days 1-5 and days 8-12. Trisenox will be restarted only when the QT interval returns to less than 500 msec. One treatment cycle consists of 2 weeks, with 14 days of cytarabine and 10 days of ATO. Subsequent cycles will be administered at the investigator's discretion, depending on response and tolerability. Patients may continue to receive treatment with Trisenox /LDAC for a period of up to 2 years as long as stable disease or clinical benefit and absence of unacceptable toxicity can be demonstrated.
DRUGcytarabine
Cytarabine will be administered at a dose of 10 mg/m2 subcutaneously (sc) twice daily (bid) from days 1-14. Trisenox will be administered at a dose of 0.25 mg/kg on days 1-5 and days 8-12. Trisenox will be restarted only when the QT interval returns to less than 500 msec. One treatment cycle consists of 2 weeks, with 14 days of cytarabine and 10 days of ATO. Subsequent cycles will be administered at the investigator's discretion, depending on response and tolerability. Patients may continue to receive treatment with Trisenox /LDAC for a period of up to 2 years as long as stable disease or clinical benefit and absence of unacceptable toxicity can be demonstrated.
Sponsors
Weill Medical College of Cornell University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients \> = 18 years with a documented history of myelofibrosis transformed to acute myeloid leukemia using the World Health Organization criteria of \> = 20% blasts in the peripheral blood or bone marrow; the diagnosis of myelofibrosis could be either primary myelofibrosis (myelofibrosis with myeloid metaplasia, agnogenic myeloid metaplasia), post-polycythemia vera or post-essential thrombocytosis. 2. Patients \> = 18 years with myelofibrosis (either primary (myelofibrosis with myeloid metaplasia, agnogenic myeloid metaplasia), post polycythemia vera or post essential thrombocytosis) who 1) meet the Mayo Clinic criteria for high risk disease (\> = 2 of the following criteria: hemoglobin \<10 g/dL, WBC \<4 or \>30 x 109/L, platelets \< 100 x 109/L, absolute monocyte count \> = 1 x 109/L) AND 2) have failed to respond to treatment with at least one prior therapy for myelofibrosis (erythropoietic cytokines, androgens, hydrea, interferon, thalidomide, lenalidomide or investigational therapy). 3. Patients must have discontinued prior myelofibrosis treatments (with the exception of hydrea, which is permitted for control of leukocytosis) for at least 14 days prior to starting study drug 4. ECOG performance status of \< = 2 5. Serum creatinine \< = 2.5 times the upper limit of normal 6. Serum bilirubin \< = 2.5 times the upper limit of normal 7. Serum potassium \>4.0 mEq/dL and serum magnesium \>2.0 mg/dL. If these serum electrolytes are below the specified limits on the baseline laboratory tests, electrolytes will be administered to bring the serum concentrations to these levels before administering arsenic trioxide. 8. Patients will be eligible for this trial regardless of gender, racial/ethnic background, provided all other inclusion and
Exclusion criteria
are met and the patient or patient's legally authorized guardian signs the informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the response rate in patients with advanced MF/LT using criteria of the International Working Group (IWG) | duration of study |
| To characterize the safety and tolerability of the regimen in this patient population | duration of study |
Secondary
| Measure | Time frame |
|---|---|
| To assess overall survival | duration of study |
Countries
United States
Outcome results
None listed