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Myelodysplastic Syndromes and Leukemia, Myeloid, AcutePhase 1NCT00671697

Decitabine, Arsenic Trioxide and Ascorbic Acid for Myelodysplastic Syndromes and Acute Myeloid Leukemia

A Phase 1 study testing Arsenic Trioxide and Decitabine in people with Myelodysplastic Syndromes and Leukemia, Myeloid, Acute, run by Washington University School of Medicine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study is designed to test the combination of decitabine, arsenic trioxide and ascorbic acid in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Arsenic Trioxide and Decitabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited States
Study dates
May 2008to May 2011
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • MDS (either de novo or secondary) fitting any of the FAB classifications or AML defined by FAB classification criteria. Patients with < 5% bone marrow blasts must also meet one of the following criteria:
  • Symptomatic anemia with either hemoglobin <10.0 g/dL or requiring red blood cell (RBC) transfusion
  • Thrombocytopenia with a history of two or more platelet counts < 50,000 / µL or a significant hemorrhage requiring platelet transfusions, or
  • Neutropenia with two or more absolute neutrophil counts < 1,000 /µL.
  • AML patients must also have a WBC < 10,000µL and meet one of the following two criteria:
  • Age greater than or equal to 60 years
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  • Relapsed AML and are not a candidate for cytotoxic chemotherapy.
  • ECOG performance status of 0-2.
  • Must give written informed consent indicating their awareness of the investigational nature of this study and its potential hazards.
  • Adequate renal and hepatic function (creatinine < 1.5x institutional upper limit of normal, total bilirubin ≤ 1.5x institutional upper limit of normal, AST and ALT ≤ 2x institutional upper limit of normal).
  • Serum potassium > 4.0 mEq/L, serum magnesium > 1.8 mg/dL.
  • Life expectancy of at least 16 weeks.
  • Women of childbearing age must have a negative serum pregnancy test prior to initiating therapy.
  • Sexually active women of childbearing potential must use effective birth control during the trial and for at least two months following the trial.
  • Men must be willing to avoid fathering a new child while receiving therapy with decitabine.
  • Greater than or equal to 18 years, no upper age limit
  • Individuals who are candidates for hematopoietic stem cell transplantation and who meet all other study criteria may participate in the study and receive intravenous decitabine in combination with arsenic trioxide and Ascorbic acid as a treatment prior to transplantation.

Who cannot join

  • Known central nervous system (CNS) leukemia.
  • Previously received greater than or equal to 5 cycles of azacitidine (Vidaza®, Pharmion Corp., Boulder, CO) or decitabine (Dacogen®, MGI Pharma Inc. Bloomington, MN).
  • QTc > 460 msec.
  • Known or suspected hypersensitivity to decitabine, arsenic or ascorbic acid.
  • Receiving any other investigational agents within 30 days of first dose of study drug.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure of NYHA class 3 or 4, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.
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  • Known positive serology for HIV.
  • Had radiotherapy within 14 days prior to study enrollment.
  • Known presence of hepatic tumors.
  • < 18 years of age
  • Exclude women who are pregnant or breast feeding.
  • Known history of glucose-6-phosphate deficiency (G6PD).
  • Currently taking a Class Ia or Class III antiarrhythmic or other medication causally associated with prolonging QTc.
  • Use of aspirin with platelet counts < 50,000/µl.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Phase I Study of Intravenous Decitabine in Combination With Arsenic Trioxide and Ascorbic Acid in Patients With Myelodysplastic Syndromes and Acute Myeloid Leukemia

This study is designed to test the combination of decitabine, arsenic trioxide and ascorbic acid in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia

Read the detailed description

Myelodysplastic syndromes (MDS) are hematological disorders characterized by ineffective hematopoiesis. DNA hypomethylating agents such as decitabine have been shown to have activity in this disorder by reversing the epigenetic mechanism of gene silencing.

Acute Myeloid Leukemia (AML) is a hematological disorder characterized by ineffective hematopoiesis and malignant expansion of clonal myeloid cells. In elderly patients (≥ 60 years old), MDS commonly precedes the diagnosis of AML. Standard therapy for AML consists of cytotoxic chemotherapy and is often followed with allogeneic stem cell transplantation. Unfortunately, elderly patients are often unable to tolerate such aggressive therapy.

Arsenic has also shown activity in patients with MDS and AML though modulation of apoptosis via increased oxidative stress. In preclinical modes, arsenic activity is related to the production of radical oxygen species that damage mitochondria. Cellular glutathione acts as a cellular antioxidant and can be depleted with the vitamin ascorbic acid which increases intracellular oxidative stress and sensitivity to arsenic trioxide induced apoptosis.

We are studying the combination of decitabine, arsenic trioxide and ascorbic acid, two primary agents and one vitamin all with different mechanisms of action in order to improve the response rate in patients with MDS and AML. This is an open-label, single-arm, single-center, dose escalation Phase I trial of decitabine, arsenic trioxide and ascorbic acid in patients with MDS, either de novo or secondary, fitting any of the FAB classifications and AML.

Being tested
Arsenic Trioxide, Decitabine
Keywords
MDS, hypomethylating agent, oxidative stress
Medical subject headings
Myelodysplastic Syndromes, Leukemia

What participants receive

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

  • Arsenic TrioxideDrug

    Also called Dacogen, Vitamin C and Trisenox

  • DecitabineDrug

    Also called Dacogen

Study groups in NCT00671697
Study groupRoleWhat they receive
Dose Level 1 Arsenic Trioxide & DecitabineExperimentalArsenic trioxide loading dose of 0.1 mg/kg/day IV x 5 days followed by weekly doses of 0.1 mg/kg IV for 15 additional weeks. Decitabine 20 mg/m2 IV every day on days 1-5 of a 4 weeks cycle for 4 cycles.
Receives: Drug: Arsenic Trioxide; Drug: Decitabine
Dose Level 2 Arsenic Trioxide & DecitabineExperimentalArsenic trioxide loading dose of 0.2 mg/kg/day IV x 5 days followed by weekly doses of 0.2 mg/kg IV for 15 additional weeks. Decitabine 20 mg/m2 IV every day on days 1-5 of a 4 weeks cycle for 4 cycles.
Receives: Drug: Arsenic Trioxide; Drug: Decitabine
Dose Level 3 Arsenic Trioxide & DecitabineExperimentalArsenic trioxide loading dose of 0.3 mg/kg/day IV x 5 days followed by weekly doses of 0.3 mg/kg IV for 15 additional weeks. Decitabine 20 mg/m2 IV every day on days 1-5 of a 4 weeks cycle for 4 cycles.
Receives: Drug: Arsenic Trioxide; Drug: Decitabine

What is being measured

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

  1. To define the maximum tolerated dose and dose-limiting toxicities during four cycles of combination decitabine, arsenic trioxide and ascorbic acid in patients with myelodysplastic syndromes (MDS) previously untreated with hypomethylating agents.

    Measured: 4 months after the final patient on the final cohort starts treatment

Secondary outcomes (8)

  1. To estimate the rate of complete remission (CR) and partial remission (PR) after four cycles of therapy in patients with MDS.

    Measured: After 4 cycles of treatment

  2. To determine the rate of hematologic improvement

    Measured: Weekly through the end of treatment

  3. To determine the rate of transfusion independence

    Measured: Through completion of treatment

  4. To determine the time to disease progression to AML

    Measured: Every 4 weeks during treatment and then every 2 months for 2 years after the first dose of study drug

  5. To determine the rate of cytogenetic response

    Measured: After every 2 cycles

  6. To determine the rate of overall survival

    Measured: Every 4 weeks during treatment and then every 2 months for 2 years after the first dose of study drug

  7. To determine changes in bone marrow vascular density

    Measured: At baseline, end of cycle 2, end of cycle 4, and end of study

  8. To determine changes in angiogenic mRNA expression.

    Measured: Baseline, end of cycle 2, end of cycle 4, and end of study

Timeline

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

  1. First posted5 May 2008 (estimated)
  2. Study startMay 2008
  3. Primary completionJan 2010
  4. Study completionMay 2011

Resources

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00671697
Sponsor's protocol ID
07-0916 / 201011797
Status last verified
May 2013
First submitted
1 May 2008
Last updated
4 Jun 2013
Results posted
No
Data monitoring committee
Yes

Publications

  • Welch JS, Klco JM, Gao F, Procknow E, Uy GL, Stockerl-Goldstein KE, Abboud CN, Westervelt P, DiPersio JF, Hassan A, Cashen AF, Vij R. Combination decitabine, arsenic trioxide, and ascorbic acid for the treatment of myelodysplastic syndrome and acute myeloid leukemia: a phase I study. Am J Hematol. 2011 Sep;86(9):796-800. doi: 10.1002/ajh.22092. Epub 2011 Aug 3. No abstract available.

    PubMed 21815182

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Arsenic Trioxide and Decitabine in people with Myelodysplastic Syndromes and Leukemia, Myeloid, Acute, run by Washington University School of Medicine at 1 site in United States.

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 17 inclusion and 14 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: finished, as of the sponsor's last update on 4 Jun 2013. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

To define the maximum tolerated dose and dose-limiting toxicities during four cycles of combination decitabine, arsenic trioxide and ascorbic acid in patients with myelodysplastic syndromes (MDS) previously untreated with hypomethylating agents. (time frame: 4 months after the final patient on the final cohort starts treatment). 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 NCT00671697, which also lists 1 linked publication.

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 4 Jun 2013.

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