Arsenic Trioxide With or Without Ascorbic Acid in Treating Patients With Myelofibrosis

This phase I trial studies the side effects and best dose of arsenic trioxide with or without ascorbic acid in treating patients with myelofibrosis. Drugs used in chemotherapy, such as arsenic trioxide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving arsenic acid together with ascorbic acid may kill more cancer cells.

PRIMARY OBJECTIVES:

I. To determine the safety and maximum tolerated dose of oral arsenic trioxide with or without ascorbic acid in subjects with myelofibrosis.

SECONDARY OBJECTIVES:

I. To estimate the incidence, severity, and attribution of treatment-emergent adverse events.

II. To estimate the rate of complete or major clinical-hematological response from treatment with arsenic trioxide and ascorbic acid in this subject population as measured by the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) response criteria.

III. To measure arsenic trioxide levels in the plasma of patients treated with and without ascorbic acid on this protocol.

IV. To estimate the efficacy of arsenic trioxide with ascorbic acid in subjects with myelofibrosis, as determined by a reduction in Janus kinase 2 (JAK2) V617F, JAK22T875N, and mutations of the thrombopoietin receptor (MPL515L/K) allele frequency in peripheral blood neutrophils.

V. To examine the effect of treatment on biological markers of myeloproliferation, cytokine production and hematopoietic stem cell mobilization. In particular, the following markers of disease will be measured: cluster of differentiation (CD)34+ cell count in peripheral blood measured by cytofluorimetry, plasma vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-B), stromal cell-derived factor-1 (SDF-1), neutrophil elastase levels by commercial assays.

VI. To examine single nucleotide polymorphism (SNP) in the arsenic trioxide pathway in subjects with myelofibrosis treated with arsenic trioxide and ascorbic acid.

OUTLINE: This is a dose-escalation study of arsenic trioxide.

Patients receive arsenic trioxide orally (PO) once daily (QD) in orange juice on days 1-21. Patients may also receive ascorbic acid PO QD on days 1-21. Treatment repeats every 28 days for up to 168 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 4 months for 1 year.

Eligibility Criteria:
Inclusion Criteria:

* Diagnosis of primary myelofibrosis, essential thrombocythemia related myelofibrosis, or polycythemia vera related myelofibrosis requiring therapy, including:

  * Those previously treated and relapsed or refractory
  * Or, if newly diagnosed, with intermediate or high risk according to Lille scoring system (adverse prognostic factors are: hemoglobin \[Hb\] \< 10 g/dl, white blood cell count \[WBC\] \< 4 or \> 30 x 10\^9/L; risk group: 0 = low, 1 = intermediate, 2 = high)
  * Or with symptomatic splenomegaly (must be \>= 23 cm by ultrasound in the longitudinal axis)
* Signed informed consent: patients must have signed consents for both the arsenic trioxide with ascorbic acid protocol and for the hematologic malignancy procurement protocol to be eligible to participate
* Patients must have been off any primary myelofibrosis (PMF)-directed experimental therapy for 4 weeks prior to entering this study and have recovered from the toxic effects (grade 0-1) of that therapy; treatment with hydroxyurea and erythropoietin are permitted until study initiation
* Serum bilirubin levels =\< 2 times the upper limit of the normal range for the laboratory (ULN); higher levels are acceptable if these can be attributed by treating physician to active hemolysis or ineffective erythropoiesis due to myelofibrosis
* Serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) levels =\< 2 x ULN
* Serum creatinine levels =\< 1.5 x ULN
* Women of childbearing potential must have a negative serum or urine pregnancy test prior to arsenic trioxide treatment and should be advised to avoid becoming pregnant
* Men must be advised to not father a child while receiving treatment with arsenic trioxide
* Both women of childbearing potential and men must practice effective methods of contraception (those generally accepted as standard of care measures)
* Women of childbearing potential are women who are not menopausal for 12 months or who have not undergone previous surgical sterilization
* If the subject is a woman of childbearing potential, she must use a medically acceptable form of contraception during the study period and for 30 days thereafter
* If the subject is a man he must be surgically sterile or must use a medically approved method of contraception for the duration of the study and for 60 days following the last dose of arsenic trioxide

Exclusion Criteria:

* Nursing and pregnant females; should a woman become pregnant or suspects she is pregnant while participating in this study, she should inform her treating physician immediately
* New York Heart Association (NYHA) grade II or greater congestive heart failure
* Unstable angina
* Corrected QT interval (QTc) \> 450 in the presence of potassium \>= 4 mEq/L and magnesium \>= 1.7 mEq/L
* Eastern Cooperative Oncology Group (ECOG) \> 2
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days, or anticipation of the need for major surgical procedure during the course of the study
* Biopsy or other minor surgical procedure, excluding placement of a vascular access device or bone marrow biopsy, within 7 days prior to study enrollment
* Ongoing serious, non-healing wound, ulcer, or bone fracture
* Known hypersensitivity to any component of arsenic trioxide