Essential ThrombocythemiaPhase 1NCT01014546

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

A Phase 1 study testing Arsenic Trioxide, Ascorbic Acid and Laboratory Biomarker Analysis in people with Essential Thrombocythemia and Polycythemia Vera, run by Roswell Park Cancer Institute at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 19 years and older
Conditions the study is for: Essential Thrombocythemia, Polycythemia Vera, Primary Myelofibrosis
What is being tested?: Arsenic Trioxide, Ascorbic Acid and Laboratory Biomarker Analysis
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 5 participants
Where: 1 siteUnited States
Study dates: Apr 2010to Feb 2015
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 19 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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

Who cannot join

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

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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

Trial locations and contacts

1 site in 1 country.

United States1 site

Roswell Park Cancer Institute
Buffalo, New York, 14263

Other trials in United States

About this study

Official title: A Phase I Study of Oral Arsenic Trioxide With or Without Ascorbic Acid in Adults With Myelofibrosis

Read the detailed description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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.

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.

Conditions: Essential Thrombocythemia, Polycythemia Vera, Primary Myelofibrosis
Being tested: Arsenic Trioxide, Ascorbic Acid, Laboratory Biomarker Analysis, Pharmacological Study
Medical subject headings: Thrombocythemia, Essential, Polycythemia Vera, Primary Myelofibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Arsenic TrioxideDrug
Also called Arsenic (III) Oxide, Arsenic Sesquioxide, Arsenous Acid, Arsenous Acid Anhydride
Given PO
Ascorbic AcidDietary supplement
Also called 2-(1,2-dihydroxyethyl)-4,5-dihydroxy-furan-3-one, Asorbicap, C Vitamin, C-Long
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
Pharmacological StudyOther
Correlative studies

Study groups in NCT01014546
Study group	Role	What they receive
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. Receives: Drug: Arsenic Trioxide; Dietary Supplement: Ascorbic Acid; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: At 28 days

Secondary outcomes (6)

Change in absolute number of circulating CD34+ cells in the peripheral blood (Stage 2 only)
Measured: Baseline to 24 weeks
Change in JAK2/MPL (Stage 2 only)
Measured: Baseline to 24 weeks
Change in plasma levels of chemokines as measured by ELISA (Stage 2)
Including: sVCAM-1, NE, MMP-2, MMP-9, SDF-1, TGF-B, and VEGF.
Measured: Baseline to 24 weeks
Change in plasma levels of cytokines as measured by ELISA (Stage 2)
Including: sVCAM-1, NE, MMP-2, MMP-9, SDF-1, TGF-B, and VEGF.
Measured: Baseline to 24 weeks
Change in plasma levels of proteases as measured by enzyme-linked immunosorbent assay (ELISA) (Stage 2)
Including: soluble vascular cell adhesion molecule 1 (sVCAM-1), neutrophil elastase (NE), matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9), stromal cell derived growth factor-1 (SDF-1), TGF-B, and VEGF.
Measured: Baseline to 24 weeks
Disease response assessed using the IWG-MRT response criteria
Measured: Up to 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2010Feb 2015

First posted17 Nov 2009 (estimated)
Study startApr 2010
Primary completionFeb 2015
Study completionFeb 2015

Why it stopped: low accrual

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Essential ThrombocythemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 5 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01014546
Sponsor's protocol ID: I 154609
Other IDs: NCI-2009-01660, I 154609
Status last verified: Jul 2022
First submitted: 16 Nov 2009
Last updated: 22 Jul 2022
Results posted: No
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1
A Study to Evaluate DMR-001 in Participants With CALR-mutant Myeloproliferative Neoplasms
Myeloproliferative Neoplasms (MPNs)
RecruitingPhase 2
Selinexor and Pacritinib in JAK Inhibitor-naïve MF Patients With Cytopenias
Myelofibrosis, Post-polycythemia Vera Myelofibrosis
RecruitingPhase 2
A Randomized Study of ASTX727 With or Without Iadademstat in Advanced Myeloproliferative Neoplasms (MPNs)
Accelerated Phase Myeloproliferative Neoplasm, Blast Phase Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Extended Access of Momelotinib in Adults With Myelofibrosis
Primary Myelofibrosis
RecruitingPhase 3
A Phase 3 Study of Pelabresib (DAK539) and Ruxolitinib in Myelofibrosis (MF)
Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis (PPV-MF)

All Essential Thrombocythemia trials

Study at a glance

From the registry record, last updated by the sponsor on 22 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I Study of Oral Arsenic Trioxide With or Without Ascorbic Acid in Adults With Myelofibrosis
ClinicalTrials.gov ID: NCT01014546
Acronym / sponsor ID: I 154609
Conditions: Essential Thrombocythemia, Polycythemia Vera, Primary Myelofibrosis
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: low accrual
Enrolment: 5 participants (actual)
Lead sponsor: Roswell Park Cancer InstituteUniversity, hospital or other
Collaborators: Cephalon, Inc.
Study start: Apr 2010
Primary completion: Feb 2015 (actual)
Study completion: Feb 2015 (actual)
First posted: 17 Nov 2009 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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

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

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.

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

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment (arsenic trioxide with or without ascorbic acid)	Experimental	Drug: Arsenic Trioxide, Dietary Supplement: Ascorbic Acid, Other: Laboratory Biomarker Analysis, Other: Pharmacological StudyPatients 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.

Who may qualify

Ages: 19 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (15 listed)

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

Key exclusion criteria (9 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Arsenic TrioxideAlso: Arsenic (III) Oxide, Arsenic Sesquioxide, Arsenous Acid, Arsenous Acid AnhydrideGiven PO	Drug	Treatment (arsenic trioxide with or without ascorbic acid)
Ascorbic AcidAlso: 2-(1,2-dihydroxyethyl)-4,5-dihydroxy-furan-3-one, Asorbicap, C Vitamin, C-LongGiven PO	Dietary supplement	Treatment (arsenic trioxide with or without ascorbic acid)
Laboratory Biomarker AnalysisCorrelative studies	Other	Treatment (arsenic trioxide with or without ascorbic acid)
Pharmacological StudyCorrelative studies	Other	Treatment (arsenic trioxide with or without ascorbic acid)

Primary outcome

Adverse events, and their attribution throughout the study
Time frame: Up to 30 days post-treatment
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.
Dose-limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 3.0 (Stage 1)
Time frame: At 28 days
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.
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)
Time frame: At 28 days
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.

6 secondary outcomes

Change in absolute number of circulating CD34+ cells in the peripheral blood (Stage 2 only)
Time frame: Baseline to 24 weeks
Change in JAK2/MPL (Stage 2 only)
Time frame: Baseline to 24 weeks
Change in plasma levels of chemokines as measured by ELISA (Stage 2)
Time frame: Baseline to 24 weeks
Change in plasma levels of cytokines as measured by ELISA (Stage 2)
Time frame: Baseline to 24 weeks
Change in plasma levels of proteases as measured by enzyme-linked immunosorbent assay (ELISA) (Stage 2)
Time frame: Baseline to 24 weeks
Disease response assessed using the IWG-MRT response criteria
Time frame: Up to 24 weeks

Results and safety

The study was stopped early (reason given: low accrual). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2022.

Related trials for Essential Thrombocythemia

RecruitingPhase 1
A Study to Evaluate DMR-001 in Participants With CALR-mutant Myeloproliferative Neoplasms
Myeloproliferative Neoplasms (MPNs)
RecruitingPhase 2
Selinexor and Pacritinib in JAK Inhibitor-naïve MF Patients With Cytopenias
Myelofibrosis, Post-polycythemia Vera Myelofibrosis
RecruitingPhase 2
A Randomized Study of ASTX727 With or Without Iadademstat in Advanced Myeloproliferative Neoplasms (MPNs)
Accelerated Phase Myeloproliferative Neoplasm, Blast Phase Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Extended Access of Momelotinib in Adults With Myelofibrosis
Primary Myelofibrosis
RecruitingPhase 3
A Phase 3 Study of Pelabresib (DAK539) and Ruxolitinib in Myelofibrosis (MF)
Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis (PPV-MF)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Eunice Wang, MD principal investigator

Roswell Park Cancer Institute

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 22 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: low accrual). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse events, and their attribution throughout the study (time frame: Up to 30 days post-treatment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01014546.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2022.