Pilot Trial of Arsenic + Cytarabine in Patients With Myelofibrosis

NCT ID: NCT00572065

Last Updated: 2017-03-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2010-02-08

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.

Conditions

Myelofibrosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

All Patients

Arsenic trioxide \[TrisenoxTM Injection\], will be administered at a dose of 0.25 mg/kg on days 1-5 and days 8-12.

Group Type: EXPERIMENTAL

arsenic trioxide

Intervention Type: DRUG

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.

cytarabine

Intervention Type: DRUG

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.

Interventions

arsenic 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.

Intervention Type: DRUG

cytarabine

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.

Intervention Type: DRUG

Other Intervention Names

cytosine arabinoside; Ara-C

Eligibility Criteria

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.

Exclusion Criteria

1. Pregnant or lactating women

2. Presence of a (9;22) translocation cytogenetically, or presence of bcr-abl by FISH (fluorescence in situ hybridization) or PCR (polymerase chain reaction)

3. Absolute QT interval >500 msec in the presence of serum potassium ≥ 4.0 mEq/L and magnesium > = 1.8 mg/dL.

4. Prior cytotoxic chemotherapy for AML or MDS; prior treatment with hydroxyurea, 5-azacytidine, decitabine, thalidomide and lenalidomide are permitted. Prior treatment with low-dose cytarabine is not permitted.

5. Concurrent treatment with maintenance therapy, cytotoxic chemotherapy, radiation, or investigational agents.

6. Uncontrolled or severe cardiovascular, pulmonary or infectious disease or other medical condition that would prohibit use of the planned study treatments.

7. Inability or unwillingness to comply with the treatment protocol, follow-up, or research tests.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gail Roboz, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

Weill Cornell Medical College

New York, New York, United States

Countries

United States

Other Identifiers

0707009291

Identifier Type: -

Identifier Source: org_study_id