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

NCT00656617 | Completed Phase 2 Results

• 2 other identifiers: 2007-0835NCI-2010-01500
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Acute Myeloid Leukemia (AML); Myelodysplastic Syndrome (MDS)

Keywords

Acute Myeloid Leukemia; (AML); Myelodysplastic syndrome; (MDS); Leukemia; Idarubicin; Cytarabine; Vorinostat; Ara-C

Outcome Measures

Primary Outcomes (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.

  PFS Evaluation at 7 months

Secondary Outcomes (1)

• Participant Response

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

Study Arms (1)

Idarubicin + Ara-C + Vorinostat

EXPERIMENTAL

Idarubicin 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).

Drug: Idarubicin; Drug: Cytarabine; Drug: Vorinostat

Interventions

Idarubicin DRUG

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

Also known as: Idamycin PFS®

Idarubicin + Ara-C + Vorinostat

Cytarabine DRUG

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

Also known as: Ara-C, Cytosine arabinoside, Cytosar-U®, DepoCyt

Idarubicin + Ara-C + Vorinostat

Vorinostat DRUG

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

Also known as: Zolinza®, SAHA, Suberoylanilide Hydroxamic Acid, MSK-390

Idarubicin + Ara-C + Vorinostat

Eligibility Criteria

• Age: 15 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center's Official Website

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia

Interventions

Idarubicin; Cytarabine; Vorinostat

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Results Point of Contact

• Title: Guillermo Garcia-Manero, MD/Professor, Leukemia Department
• Organization: University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-745-3428

Study Officials

• Guillermo Garcia-Manero, M.D.

  M.D. Anderson Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2008
• First Posted: April 11, 2008
• Study Start: April 1, 2008
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: March 9, 2015
• Results First Posted: March 9, 2015

Record last verified: 2015-02

Locations

US (1)