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Acute Myeloid Leukemia (AML)Phase 2NCT00656617

Phase II Study of Idarubicin, Cytarabine, and Vorinostat With High-Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)

A Phase 2 study testing Idarubicin, Cytarabine and Vorinostat in people with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS), run by M.D. Anderson Cancer Center 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

The goal of this clinical research study is to find the highest safe dose of vorinostat that can be given in combination with idarubicin and ara-C for the treatment of AML and high-risk MDS. Read more about this study

Who is it for?
Ages 15 to 65 years
What is being tested?
Idarubicin, Cytarabine and Vorinostat
Could I receive a placebo?
No, everyone receives an active treatment
How many people
106 participants
Where
1 siteUnited States
Study dates
Apr 2008to Feb 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 15 to 65 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Diagnosis of 1) AML (World Health Organization (WHO) classification definition of >/= 20% blasts), or 2) intermediate-2 or high-risk MDS (defined by the IPSS classification2).
  • Patients aged 15 to 65 years;
  • For the initial run-in phase of the study, patients with relapsed or refractory disease or patients with secondary untreated disease are eligible, however, these patients must not have had prior exposure to a histone deacetylase inhibitor, prior antecedent hematological disorder or secondary disease with complex cytogenetics.
  • For the actual phase II portion of the study: patients must be chemonaïve, i.e., not have received any chemotherapy (except hydrea) for AML or MDS. They may have received hypomethylating agents for prior MDS and transfusions, hematopoietic growth factors or vitamins. Temporary prior measures such as apheresis or hydrea are allowed;
  • In those patients that have received prior therapy, at least 2 weeks need to have elapsed before participating in this study. Treatment may start earlier if deemed in the best interest of the patient after discussion with the PI of the study ;
  • Eastern Cooperative Oncology Group (ECOG) performance status </= 2
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  • Serum biochemical values with the following limits unless considered due to leukemia: creatinine </=2 mg/dl; total bilirubin </=2 mg/dL, unless increase is due to hemolysis or congenital disorder; transaminases (SGPT or SGOT) </=2.5* upper limit of normal (ULN);
  • Ability to swallow oral medication;
  • Ability to understand and provide signed informed consent;
  • Cardiac ejection fraction must be >/=50% (by either multiple gated acquisition scan (MUGA) scan or echocardiography).
  • Diagnosis of 1) AML (WHO classification definition of > 20% blasts), or 2) intermediate-2 or high-risk MDS (defined by the International Prognostic Scoring System (IPSS) classification) with Flt-3 mutation. Flt-3 extension phase.
  • Patients aged 15 to 65 years are eligible. Flt-3 extension phase.
  • Patients with relapsed or refractory disease or patients with secondary untreated disease are eligible, however, these patients must not have had prior exposure to a histone deacetylase inhibitor. All patients should be Flt-3 positive. Flt-3 extension phase.
  • Patients with newly diagnosed Flt3 positive AML are allowed. Flt-3 extension phase.
  • In those patients that have received prior therapy, at least 2 weeks need to have elapsed before participating in this study. Treatment may start earlier if deemed in the best interest of the patient after discussion with the PI of the study. Flt-3 extension phase.
  • ECOG performance status </= 2. Flt-3 extension phase.
  • Serum biochemical values with the following limits unless considered due to leukemia. creatinine </=2 mg/dl; total bilirubin </=2 mg/dL, unless increase is due to hemolysis or congenital disorder - transaminases (SGPT or SGOT) </=2.5* ULN. Flt-3 extension phase.
  • Ability to swallow oral medication. Flt-3 extension phase.
  • Ability to understand and provide signed informed consent. Flt-3 extension phase.
  • Cardiac ejection fraction must be >/=50% (by either MUGA scan or echocardiography). Flt-3 extension phase.

Who cannot join

  • Diagnosis of acute promyelocytic leukemia;
  • Active, uncontrolled, systemic infection considered opportunistic, life threatening or clinical significant at the time of treatment, or any severe concurrent disease, which in the opinion of the investigator and after discussion with the principal investigator, would make the patient inappropriate for study entry;
  • Male and female patients who are fertile agree to use an effective barrier method of birth control (i.e., latex condom, diaphragm, cervical cap, etc.) to avoid pregnancy. Female patients need a negative serum or urine pregnancy test within 7 days of study enrollment (applies only if patient of childbearing potential. Non childbearing is defined as 1 year or more postmenopausal or surgically sterilized);
  • Symptomatic central nervous system (CNS) involvement;
  • Patient is unable to take and/or tolerate oral medications on a continuous basis;
  • Patient has known human immunodeficiency virus (HIV) infection or known HIV-related malignancy;
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  • Patient has active hepatitis B or C infection. Active disease is defined as elevated liver enzymes and/or clinical symptoms of hepatitis in addition to positive blood test for hepatitis surface antigen. In the absence of elevated liver enzymes and/or clinical symptoms, the blood test for hepatitis core antigens is not required.
  • Patient is pregnant or breast-feeding;
  • Patient has a known allergy or hypersensitivity to any component of vorinostat;
  • Patient has a history of thrombotic disorders;
  • History of any psychiatric condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent.
  • Diagnosis of acute promyelocytic leukemia. Flt-3 extension phase.
  • Active, uncontrolled, systemic infection considered opportunistic, life threatening or clinical significant at the time of treatment, or any severe concurrent disease, which in the opinion of the investigator and after discussion with the principal investigator, would make the patient inappropriate for study entry. Flt-3 extension phase.
  • Male and female patients who are fertile agree to use an effective barrier method of birth control (i.e., latex condom, diaphragm, cervical cap, etc.) to avoid pregnancy. Female patients need a negative serum or urine pregnancy test within 7 days of study enrollment (applies only if patient of childbearing potential. Non childbearing is defined as 1 year or more postmenopausal or surgically sterilized). Flt-3 extension phase.
  • Symptomatic CNS involvement. Flt-3 extension phase.
  • Patient is unable to take and/or tolerate oral medications on a continuous basis. Flt-3 extension phase.
  • Patient has known human immunodeficiency virus (HIV) infection or known HIV-related malignancy. Flt-3 extension phase.
  • Patient has active hepatitis B or C infection. Active disease is defined as elevated liver enzymes and/or clinical symptoms of hepatitis in addition to positive blood test for hepatitis surface antigen. In the absence of elevated liver enzymes and/or clinical symptoms, the blood test for hepatitis core antigens is not required. Flt-3 extension phase.
  • Patient is pregnant or breast-feeding. Flt-3 extension phase.
  • Patient has a known allergy or hypersensitivity to any component of vorinostat. Flt-3 extension phase.
  • Patient has a history of thrombotic disorders. Flt-3 extension phase.
  • History of any psychiatric condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent. Flt-3 extension phase.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • The University of Texas M.D. Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase II Study of Idarubicin, Cytarabine, and Vorinostat in Patients With High-Risk MDS and AML

The goal of this clinical research study is to find the highest safe dose of vorinostat that can be given in combination with idarubicin and ara-C for the treatment of AML and high-risk MDS.

Once the highest safe dose is found, researchers will then try to learn if this combination treatment can help to control AML and high-risk MDS in newly diagnosed patients. The safety of this treatment combination will also be studied.

Read the detailed description

The Study Drugs:

Vorinostat is designed to change the gene expression profile of leukemia cells, which may cause the cells to die.

Idarubicin is designed to cause breaks in DNA (the genetic material of cells). This may cause cancer cells to die.

Ara-C is designed to insert itself into DNA of cancer cells and stop the DNA from repairing itself.

This dose combination has not been tested in humans before, at this dose level and schedule.

Study Drug Administration:

Induction Therapy:

If you are found to be eligible to take part in this study, you will begin induction therapy. During induction therapy, the dose level of vorinostat may vary based on when you join the study and on the side effects seen in other participants. The first group of 3 participants will receive the highest dose level of vorinostat. If intolerable side effects are experienced, the next group of 3 participants will receive a lower dose of vorinostat. This will continue until the highest dose of vorinostat with no intolerable side effects is found. The dose levels of the other drugs will not change.

In the Induction phase, you will receive 1 or 2 induction cycles of therapy on the following schedule:

  • On Days 1-3, you will take vorinostat by mouth 3 times a day.
  • On Days 4-6, you will receive idarubicin through a needle in your vein over 1 hour.
  • On Days 4-7, you will receive ara-C by vein as a non-stop infusion.
  • On Days 4-7, you will receive solumedrol or dexamethasone to help reduce the risk of side effects associated with ara-C. The drug will be given by vein over a few seconds.

Consolidation Therapy:

If the disease responds during Induction, you may be able to receive up to 5 additional 4-6 week study cycles. During these Consolidation Cycles, you will take the study drugs on the following cycle:

  • On Days 1-3, you will take vorinostat by mouth 3 times a day.
  • On Days 4 and 5, you will receive idarubicin through a needle in your vein over 5 minutes.
  • On Days 4-6, you will receive ara-C by vein as a non-stop infusion.
  • On Days 4 and 5, you will also receive either solumedrol or dexamethasone by vein over a few seconds.

Maintenance Therapy:

If you go into remission, you will begin maintenance therapy. While on maintenance therapy, you will take vorinostat by mouth 3 times a day on Days 1-14 of each 28-day study cycle. You may have up to 12 Maintenance Cycles.

Study Visits:

At least every week during Cycle 1, and then at least once a month during each additional cycle, blood (about 1-2 teaspoons) will be drawn for routine tests. You will also have routine bone marrow aspirates and biopsies before initiating treatment and approximately on Day 21 and Day 28 after initiating therapy.

Length of Study:

You may continue to receive the study drugs for up to 18 cycles. You will be taken off study early if the disease gets worse or intolerable side effects occur.

This is an investigational study. Idarubicin is FDA approved for use in combination with other approved drugs for the treatment of AML. Vorinostat is FDA approved and commercially available for the treatment of some forms of cutaneous lymphoma. Ara-C is FDA approved for use in the treatment of leukemia. The use of these drugs together is investigational.

Up to 105 patients will take part in this study. All will be enrolled at MD Anderson.

Keywords
Acute Myeloid Leukemia, (AML), Myelodysplastic syndrome, (MDS), Leukemia, Idarubicin, Cytarabine, Vorinostat, Ara-C
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia

What participants receive

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

  • IdarubicinDrug

    Also called Idamycin PFS®

    12 mg/m^2 IV over 1 hour daily for 3 days (days 4 to 6)

  • CytarabineDrug

    Also called Ara-C, Cytosine arabinoside, Cytosar-U®, DepoCyt

    1.5 g/m^2 IV as a continuous infusion over 24 hours daily (days 4 to 7)

  • VorinostatDrug

    Also called Zolinza®, SAHA, Suberoylanilide Hydroxamic Acid, MSK-390

    Initial dose level 500 mg orally three times a day for 3 days (days 1 to 3).

Study groups in NCT00656617
Study groupRoleWhat they receive
Idarubicin + Ara-C + VorinostatExperimentalIdarubicin 12 mg/m^2 by vein (IV) over 1 hour daily for 3 days (days 4 to 6). Ara-C (Cytarabine) 1.5 g/m^2 IV as a continuous infusion over 24 hours daily (days 4 to 7). Vorinostat initial dose level 500 mg orally three times a day for 3 days (days 1 to 3).
Receives: Drug: Idarubicin; Drug: Cytarabine; Drug: Vorinostat

What is being measured

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

  1. Progression Free Survival (PFS) at 7 Months

    Progression-free survival defined as time from date of randomization to first occurrence of having documented disease progression or death due to any cause, whichever comes first. Progression based on tumor assessments according to Response Evaluation Criteria in Solid Tumors (RECIST). Participants were followed from baseline to disease progression with PFS evaluation at 7 months.

    Measured: PFS Evaluation at 7 months

Secondary outcomes (1)

  1. Participant Response

    Number of participants with response assessed according RECIST: Complete Response (CR) defined as normalization of marrow (< 5% blasts) and of peripheral blood counts (neutrophil count > 1.109/L, platelet count > 100 x 109/L). Partial response (PR) defined as for CR in terms of peripheral counts but with reduction of marrow blasts by >50% compared to pretreatment values but above <5%. Complete Response without platelet recovery (CRp) = CR, but platelets <100 x 109/L. Progressive disease (PD) defined as increase of blasts to > 10% after an initial response.

    Measured: Monitoring with each 4 week cycle, up to 18 cycles of treatment

Timeline

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

  1. First posted11 Apr 2008 (estimated)
  2. Study startApr 2008
  3. Primary completionFeb 2014
  4. Study completionFeb 2014

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
106 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00656617
Sponsor's protocol ID
2007-0835
Other IDs
NCI-2010-01500
Status last verified
Feb 2015
First submitted
7 Apr 2008
Last updated
9 Mar 2015
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Idarubicin, Cytarabine and Vorinostat in people with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS), run by M.D. Anderson Cancer Center 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 20 inclusion and 22 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 9 Mar 2015. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Progression Free Survival (PFS) at 7 Months (time frame: PFS Evaluation at 7 months). 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 NCT00656617.

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 9 Mar 2015.

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