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Previously Treated Myelodysplastic SyndromePhase 1NCT01130506

Decitabine, Vorinostat, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

A Phase 1 study testing Cytarabine, Decitabine and Laboratory Biomarker Analysis in people with Previously Treated Myelodysplastic Syndrome and Recurrent Adult Acute Myeloid Leukemia, run by National Cancer Institute (NCI) at 2 sites 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 the best dose of cytarabine when given together with decitabine and vorinostat in treating patients with acute myeloid leukemia or myelodysplastic syndrome that has returned or has not responded to treatment. Read more about this study

Who is it for?
Ages 18 to 59 years
What is being tested?
Cytarabine, Decitabine and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
2 sitesUnited States
Study dates
17 May 2010to 19 Nov 2012
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 59 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Patients with relapsed or refractory acute myeloid leukemia (AML)
  • Patients aged between 55-59.9 with previously untreated AML will also be eligible, but these patients must be screened for AML-core binding factor (CBF)+ AML is NOT eligible in this subset of previously untreated AML patients
  • Patients with relapsed or refractory high risk MDS (defined as International Prognostic Scoring System [IPSS] score >= 1.5) will also be eligible; IPSS score can be calculated any time from myelodysplastic syndrome (MDS) diagnosis at relapse/treatment failure for the purposes of trial eligibility
  • Patients with secondary AML or therapy related disease (t-AML) are eligible; patients who received decitabine or 5-azacytidine as prior treatment for MDS (or AML) are eligible; patients who previously received high dose cytarabine (>= 1 gm/m^2/dose) are eligible
  • If the patient has co-morbid medical illness, life expectancy attributed to this must be greater than 6 months
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
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  • Total bilirubin < 2.0 mg/dL
  • 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 < 2.0 mg/dL
  • New York Heart Association (NYHA) congestive heart failure (CHF) class II or better
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; if the patient does not agree, the patient is not eligible; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and willingness to sign the written informed consent document
  • Patients with known human immunodeficiency virus (HIV) infection without a history of acquired immune deficiency syndrome (AIDS) and with sufficiently high cluster of differentiation (CD)4 cells (> 400/mm^3) and low HIV viral loads (< 30,000 copies/ml plasma) not requiring anti-HIV therapy are eligible
  • Patients must have recovered from the 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, or those who have not recovered from adverse events (to less than grade 2) due to agents administered more than 4 weeks earlier
  • Patients may not have taken valproic acid, or any other histone deacetylase inhibitor, for at least 2 weeks prior to study enrollment
  • Patients receiving any other investigational agents or patients that have received other investigational agents within 14 days of enrollment
  • Patients with active central nervous system disease or with granulocytic sarcoma as sole site of disease
  • Patients with history of medically serious allergic reactions attributed to decitabine, vorinostat, or cytarabine or compounds of similar chemical or biologic composition that are not easily managed
  • Patients with the following will be excluded: 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, myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; patients with medical comorbidities that will preclude safety evaluation of the combination should not be enrolled
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  • Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study
  • Pregnant women or women who are breastfeeding; breastfeeding should be discontinued; confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women
  • Patients with advanced malignant solid tumors are excluded; patients with active additional hematologic malignancies are excluded
  • Patients with a history of neurologic toxicity with cytarabine or vorinostat are excluded
  • Patients with active infection are permitted to enroll provided that the infection is under control; patients with uncontrolled infection shall not be enrolled until infection is treated and brought under control
  • Patients who are unable to swallow pills are excluded
  • Patients requiring warfarin are excluded

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase I Study of Decitabine, Vorinostat, and Cytarabine in Acute Myeloid Leukemia

This phase I trial studies the side effects and the best dose of cytarabine when given together with decitabine and vorinostat in treating patients with acute myeloid leukemia or myelodysplastic syndrome that has returned or has not responded to treatment. Drugs used in chemotherapy, such as cytarabine and decitabine, 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. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving cytarabine together with decitabine and vorinostat may kill more cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) of the combination of decitabine, vorinostat, and cytarabine in patients with relapsed/refractory acute myeloid leukemia (AML) and select subsets of high risk leukemia/myelodysplastic syndromes (MDS).

II. To define the specific toxicities and the dose limiting toxicity (DLT) of the combination.

SECONDARY OBJECTIVES:

  1. To develop a platform for specifically targeting mixed-lineage leukemia partial-tandem duplication (MLL PTD), for future efficacy studies.

II. To determine the overall response rate (ORR) of this regimen in relapsed/ refractory AML.

III. To examine the role of decitabine and vorinostat in re-expression of mixed-lineage leukemia wild type (MLL- WT) in patients with MLL PTD via correlative studies specific to patients with MLL PTD and the preliminary relationship of this to clinical response in patients with MLL PTD+ AML.

IV. To correlate the biological activity of decitabine as demethylating agent (changes in target gene methylation and gene expression, deoxyribonucleic acid [DNA] [cytosine-5-]-methyltransferase 1 [DNMT1] protein expression, global methylation) with clinical endpoints.

  1. To explore the biologic role of microribonucleic acids (RNAs) in determining clinical response to the combination and achievement of the other pharmacodynamic endpoints.

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

INDUCTION THERAPY: Patients receive decitabine intravenously (IV) over 1 hour on days 1-10; vorinostat orally (PO) on days 5-10; and high-dose cytarabine IV over 2 hours on days 12, 14, and 16 in the absence of disease progression or unacceptable toxicity. Patients who achieve complete remission (CR) proceed to maintenance therapy. Patients who achieve CR with incomplete blood count recovery undergo bone marrow aspiration and biopsy at count recovery or day 42 before proceeding to maintenance therapy.

MAINTENANCE THERAPY: Patients receive decitabine IV over 1 hour on days 1-5 and vorinostat PO on days 5-10. Treatment repeats every 28 days for up to 11 courses in the absence of disease progression or unacceptable toxicity.

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

Being tested
Cytarabine, Decitabine, Laboratory Biomarker Analysis, Pharmacological Study, Vorinostat
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.

  • 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

  • DecitabineDrug

    Also called 5-Aza-2'-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • VorinostatDrug

    Also called L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid

    Given PO

Study groups in NCT01130506
Study groupRoleWhat they receive
Treatment (decitabine, vorinostat, cytarabine)ExperimentalINDUCTION THERAPY: Patients receive decitabine IV over 1 hour on days 1-10; vorinostat PO on days 5-10; and high-dose cytarabine IV over 2 hours on days 12, 14, and 16 in the absence of disease progression or unacceptable toxicity. Patients who achieve CR proceed to maintenance therapy. Patients who achieve CR with incomplete blood count recovery undergo bone marrow aspiration and biopsy at count recovery or day 42 before proceeding to maintenance therapy. MAINTENANCE THERAPY: Patients receive decitabine IV over 1 hour on days 1-5 and vorinostat PO on days 5-10. Treatment repeats every 28 days for up to 11 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Cytarabine; Drug: Decitabine; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Vorinostat

What is being measured

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

  1. Correlative biologic studies

    Standard paired statistical tests, parametric and nonparametric, will be used to compare to baseline treatment values. With data collected serially over time, repeated measures analysis of variance will be used to analyze data.

    Measured: Baseline up to 30 days past last dose of study drug

  2. Maximum tolerated dose (MTD) of decitabine and vorinostat, determined according to incidence of dose limiting toxicity (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    MTD of decitabine and vorinostat will be determined according to incidence of DLT graded using NCI CTCAE version 4.0. Data collected will be descriptive and provide limited estimates of variability given the small sample sizes at each dose level.

    Measured: Up to 28 days

Timeline

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

  1. First posted26 May 2010 (estimated)
  2. Study start17 May 2010
  3. Primary completion19 Nov 2012

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
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01130506
Sponsor's protocol ID
NCI-2011-01488
Other IDs
NCI-2011-01488, 2010C0009, OSU # 09150, CDR0000673876, 8485, 8485, P30CA016058, U01CA076576
Status last verified
Jul 2017
First submitted
25 May 2010
Last updated
2 Aug 2017
Results posted
No
Data monitoring committee
No

Publications

  • Mims AS, Mishra A, Orwick S, Blachly J, Klisovic RB, Garzon R, Walker AR, Devine SM, Walsh KJ, Vasu S, Whitman S, Marcucci G, Jones D, Heerema NA, Lozanski G, Caligiuri MA, Bloomfield CD, Byrd JC, Piekarz R, Grever MR, Blum W. A novel regimen for relapsed/refractory adult acute myeloid leukemia using a KMT2A partial tandem duplication targeted therapy: results of phase 1 study NCI 8485. Haematologica. 2018 Jun;103(6):982-987. doi: 10.3324/haematol.2017.186890. Epub 2018 Mar 22.

    PubMed 29567781

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cytarabine, Decitabine and Laboratory Biomarker Analysis in people with Previously Treated Myelodysplastic Syndrome and Recurrent Adult Acute Myeloid Leukemia, run by National Cancer Institute (NCI) at 2 sites 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 14 inclusion and 13 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 2 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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?

Correlative biologic studies (time frame: Baseline up to 30 days past last dose of study drug). The study lists 2 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 NCT01130506, 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 2 Aug 2017.

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