AzTrials
AzTrials

Recurrent Adult Acute Myeloid LeukemiaPhase 1NCT01249430

Azacitidine in Combination With Mitoxantrone, Etoposide Phosphate, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

A Phase 1 study testing Azacitidine, Cytarabine and Etoposide Phosphate in people with Recurrent Adult Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by National Cancer Institute (NCI) 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 phase I trial studies the side effects and best dose of azacitidine when given together with mitoxantrone, etoposide phosphate, and cytarabine in treating patients with acute myeloid leukemia that has returned after a period of improvement or does not respond to treatment. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Azacitidine, Cytarabine and Etoposide Phosphate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteUnited States
Study dates
20 Jan 2011to 24 May 2013
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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically or cytologically confirmed relapsed or refractory acute myeloid leukemia (AML) according to 2008 World Health Organization (WHO) classification; must have failed at least one cycle of induction chemotherapy or relapsed after achieving a complete remission following induction chemotherapy; patients with prior autologous or allogeneic stem cell transplant are permitted
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 6 months for any comorbid conditions
  • Total bilirubin =< 1.5 X institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
  • Creatinine =< 1.5 mg/dL
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  • Left ventricular ejection fraction >= 40%
  • Ability to understand and the willingness to sign a written informed consent document
  • Patients must have recovered from the non-hematologic toxicity of prior therapy to less than grade 2

Who cannot join

  • Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
  • Patients receiving any other investigational agents or patients that have received any other investigational agents within 14 days of enrollment
  • Patients with active central nervous system disease or with granulocytic sarcoma as sole site of disease
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to azacitidine, mannitol, or other agents used in study
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; patients with active infection are permitted to enroll provided that the infection is under control; myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any echocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with azacitidine
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: A Phase 1 Study of Azacitidine in Combination With MEC (Mitoxantrone, Etoposide, Cytarabine) in Relapsed and Refractory Acute Myeloid Leukemia

This phase I trial studies the side effects and best dose of azacitidine when given together with mitoxantrone, etoposide phosphate, and cytarabine in treating patients with acute myeloid leukemia that has returned after a period of improvement or does not respond to treatment. Azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as mitoxantrone, etoposide phosphate, and cytarabine, 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. Azacitidine may help mitoxantrone, etoposide phosphate, and cytarabine work better by making cancer cells more sensitive to the drugs.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum-tolerated dose of azacitidine (5-azaC) when combined with mitoxantrone hydrochloride (mitoxantrone), etoposide phosphate (etoposide), and cytarabine (MEC) as salvage chemotherapy in patients with relapsed or refractory acute myeloid leukemia (AML).

SECONDARY OBJECTIVES:

  1. To define the qualitative and quantitative toxicities of 5-azaC with MEC in combination with regard to organ specificity, time course, predictability, and reversibility.

II. To document the rate of complete remission (CR) and CR with incomplete blood count recovery (CRi) for this combination of agents as well as overall survival, relapse-free survival, and event-free survival.

III. To evaluate the pharmacokinetics of 5-azaC when given in combination with MEC in patients enrolled on this study.

IV. To measure R2 downregulation, including changes in R2 target, AraCTP, and dNTP/NTP pools, of 5-azaC in combination with MEC and correlate these pharmacodynamic endpoints with clinical response.

VI. To evaluate hypomethylation, including DMNT1 expression, Sp1 expression, global deoxyribonucleic acid (DNA) methylation, gene expression profiling, and micro ribonucleic acid (RNA) expression profiling, of 5-azaC when given in combination with MEC and correlate these pharmacodynamic changes with clinical response.

OUTLINE: This is a dose-escalation study of azacitidine.

Patients receive azacitidine intravenously (IV) over 30 minutes on days 1-8 and mitoxantrone hydrochloride IV over 10 minutes, etoposide phosphate IV over 30-60 minutes, and cytarabine IV over 6 hours on days 3-8. Treatment continues for 1 course in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Being tested
Azacitidine, Cytarabine, Etoposide Phosphate, Laboratory Biomarker Analysis, Mitoxantrone Hydrochloride
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

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

  • AzacitidineDrug

    Also called 5 AZC, 5-AC, 5-Azacytidine, 5-AZC

    Given IV

  • CytarabineDrug

    Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone

    Given IV

  • Etoposide PhosphateDrug

    Also called Etopophos

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Mitoxantrone HydrochlorideDrug

    Also called CL 232315, DHAD, DHAQ, Dihydroxyanthracenedione Dihydrochloride

    Given IV

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT01249430
Study groupRoleWhat they receive
Treatment (azacitidine, mitoxantrone, etoposide, cytarabine)ExperimentalPatients receive azacitidine IV over 30 minutes on days 1-8 and mitoxantrone hydrochloride IV over 10 minutes, etoposide phosphate IV over 30-60 minutes, and cytarabine IV over 6 hours on days 3-8. Treatment continues for 1 course in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Azacitidine; Drug: Cytarabine; Drug: Etoposide Phosphate; Other: Laboratory Biomarker Analysis; Drug: Mitoxantrone Hydrochloride; Other: Pharmacological Study

What is being measured

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

  1. Maximum-tolerated dose of azacitidine when combined with salvage chemotherapy (mitoxantrone hydrochloride, etoposide, and cytarabine [MEC]) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0

    Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.

    Measured: Up to day 42

Secondary outcomes (2)

  1. Clinical response according to the International Working Group criteria

    Responses will be summarized by simple descriptive summary statistics delineating complete and lesser responses as well as stable and progressive disease.

    Measured: Up to day 42

  2. Qualitative and quantitative toxicities of azacitidine in combination with (mitoxantrone hydrochloride, etoposide, and cytarabine [MEC])

    Graded according to NCI CTCAE version 4.0.

    Measured: Up to 30 days post-therapy

Timeline

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

  1. First posted29 Nov 2010 (estimated)
  2. Study start20 Jan 2011
  3. Primary completion24 May 2013
  4. Study completion24 May 2013

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01249430
Sponsor's protocol ID
NCI-2011-02554
Other IDs
NCI-2011-02554, CDR0000689575, OSU-10093, OSU 10093, 8803, 8803, P30CA016058, U01CA076576
Status last verified
Sep 2017
First submitted
25 Nov 2010
Last updated
21 Sep 2017
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Azacitidine, Cytarabine and Etoposide Phosphate in people with Recurrent Adult Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by National Cancer Institute (NCI) 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 9 inclusion and 7 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 21 Sep 2017. 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?

Maximum-tolerated dose of azacitidine when combined with salvage chemotherapy (mitoxantrone hydrochloride, etoposide, and cytarabine [MEC]) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 (time frame: Up to day 42). 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 NCT01249430.

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 21 Sep 2017.

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