Pilot Trial of Arsenic + Cytarabine in Patients With Myelofibrosis

NCT00572065 | Completed Early Phase 1

• 1 other identifier: 0707009291
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• To assess overall survival

  duration of study

Study Arms (1)

All Patients

EXPERIMENTAL

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

Drug: arsenic trioxide; Drug: cytarabine

Interventions

arsenic trioxide 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.

All Patients

cytarabine 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.

Also known as: cytosine arabinoside, Ara-C

All Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).
• 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
• ECOG performance status of \< = 2
• Serum creatinine \< = 2.5 times the upper limit of normal
• Serum bilirubin \< = 2.5 times the upper limit of normal
• 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.

You may not qualify if:

• Pregnant or lactating women
• Presence of a (9;22) translocation cytogenetically, or presence of bcr-abl by FISH (fluorescence in situ hybridization) or PCR (polymerase chain reaction)
• Absolute QT interval \>500 msec in the presence of serum potassium ≥ 4.0 mEq/L and magnesium \> = 1.8 mg/dL.
• 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.
• Concurrent treatment with maintenance therapy, cytotoxic chemotherapy, radiation, or investigational agents.
• Uncontrolled or severe cardiovascular, pulmonary or infectious disease or other medical condition that would prohibit use of the planned study treatments.
• Inability or unwillingness to comply with the treatment protocol, follow-up, or research tests.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

Arsenic Trioxide; Cytarabine

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Gail Roboz, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2007
• First Posted: December 12, 2007
• Study Start: February 29, 2008
• Primary Completion: December 1, 2009
• Study Completion: February 8, 2010
• Last Updated: March 3, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)