Pilot Trial of Arsenic + Cytarabine in Patients With Myelofibrosis

Prospective Pilot Trial of Arsenic Trioxide (Trisenox®) in Combination With Cytosine Arabinoside in Patients With Advanced or Transformed Myelofibrosis

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.

Study Overview

• Status: Completed
• Conditions: Myelofibrosis
• Intervention / Treatment: Drug: arsenic trioxide; Drug: cytarabine

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: 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.; 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.; Other Names: Ara-C; cytosine arabinoside

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Time Frame
To assess overall survival	duration of study

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Investigators: Principal Investigator: Gail Roboz, MD, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): February 29, 2008
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): February 8, 2010

Study Registration Dates

• First Submitted: December 11, 2007
• First Submitted That Met QC Criteria: December 11, 2007
• First Posted (Estimate): December 12, 2007

Study Record Updates

• Last Update Posted (Actual): March 3, 2017
• Last Update Submitted That Met QC Criteria: March 2, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Primary Myelofibrosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Arsenic Trioxide; Cytarabine
• Other Study ID Numbers: 0707009291

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO