NCT01014546

Brief Summary

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.

Trial Health

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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
5

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Apr 2010

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 16, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

November 17, 2009

Completed
5 months until next milestone

Study Start

First participant enrolled

April 1, 2010

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2015

Completed
Last Updated

July 22, 2022

Status Verified

July 1, 2022

Enrollment Period

4.8 years

First QC Date

November 16, 2009

Last Update Submit

July 20, 2022

Conditions

Essential ThrombocythemiaPolycythemia VeraPrimary Myelofibrosis

Outcome Measures

Primary Outcomes (3)

  • Adverse events, and their attribution throughout the study

    The frequency of toxicities will be tabulated by grade across all dose levels and courses. The frequency of toxicities will also be tabulated for the dose chosen as the MTD.

    Up to 30 days post-treatment

  • Dose-limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 3.0 (Stage 1)

    DLT is defined as any non-hematologic treatment-emergent grade 3 or greater adverse event deemed possibly, probably, or definitely related to the study drug. Exceptions are grade 3 nausea or vomiting, unless in the setting of maximal antiemetic treatment. Hematologic toxicities are not included in the definition of a DLT. The frequency of toxicities will be tabulated by grade across all dose levels and cycles.

    At 28 days

  • Maximum tolerated dose (MTD), defined as the dose level at which 0 or 1 of 6 subjects experience DLT, and 2 of 3 or 2 of 6 experience DLT at the next higher dose level, assessed by the NCI CTC version 3.0 (Stage 1)

    The frequency of toxicities will be tabulated by grade across all dose levels and cycles. The frequency of toxicities will also be tabulated for the dose chosen as the MTD.

    At 28 days

Secondary Outcomes (6)

  • Change in absolute number of circulating CD34+ cells in the peripheral blood (Stage 2 only)

    Baseline to 24 weeks

  • Change in JAK2/MPL (Stage 2 only)

    Baseline to 24 weeks

  • Change in plasma levels of chemokines as measured by ELISA (Stage 2)

    Baseline to 24 weeks

  • Change in plasma levels of cytokines as measured by ELISA (Stage 2)

    Baseline to 24 weeks

  • Change in plasma levels of proteases as measured by enzyme-linked immunosorbent assay (ELISA) (Stage 2)

    Baseline to 24 weeks

  • +1 more secondary outcomes

Study Arms (1)

Treatment (arsenic trioxide with or without ascorbic acid)

EXPERIMENTAL

Patients receive arsenic trioxide PO 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.

Drug: Arsenic TrioxideDietary Supplement: Ascorbic AcidOther: Laboratory Biomarker AnalysisOther: Pharmacological Study

Interventions

Arsenic TrioxideDRUG

Given PO

Also known as: Arsenic (III) Oxide, Arsenic Sesquioxide, Arsenous Acid, Arsenous Acid Anhydride, Arsenous Oxide, Trisenox, White Arsenic
Treatment (arsenic trioxide with or without ascorbic acid)
Ascorbic AcidDIETARY_SUPPLEMENT

Given PO

Also known as: 2-(1,2-dihydroxyethyl)-4,5-dihydroxy-furan-3-one, Asorbicap, C Vitamin, C-Long, Ce-Vi-Sol, Cecon, Cenolate, Cetane, Cevalin, L-Ascorbic Acid, VIT C, Vitamin C, Vitamin-C
Treatment (arsenic trioxide with or without ascorbic acid)
Laboratory Biomarker AnalysisOTHER

Correlative studies

Treatment (arsenic trioxide with or without ascorbic acid)
Pharmacological StudyOTHER

Correlative studies

Treatment (arsenic trioxide with or without ascorbic acid)

Eligibility Criteria

Age19 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Thrombocythemia, EssentialPolycythemia VeraPrimary Myelofibrosis

Interventions

Arsenic Trioxidearsenous acidAscorbic Acid

Condition Hierarchy (Ancestors)

Blood Coagulation DisordersHematologic DiseasesHemic and Lymphatic DiseasesThrombocytosisBlood Platelet DisordersMyeloproliferative DisordersBone Marrow DiseasesHemorrhagic DisordersBone Marrow NeoplasmsHematologic NeoplasmsNeoplasms by SiteNeoplasms

Intervention Hierarchy (Ancestors)

ArsenicalsInorganic ChemicalsOxidesOxygen CompoundsSugar AcidsAcids, AcyclicCarboxylic AcidsOrganic ChemicalsHydroxy AcidsCarbohydrates

Study Officials

  • Eunice Wang, MD

    Roswell Park Cancer Institute

    PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

First Submitted

November 16, 2009

First Posted

November 17, 2009

Study Start

April 1, 2010

Primary Completion

February 1, 2015

Study Completion

February 1, 2015

Last Updated

July 22, 2022

Record last verified: 2022-07

Locations

US(1)