Decitabine, Cytarabine, and Daunorubicin Hydrochloride in Treating Patients With Acute Myeloid Leukemia

NCT01627041 | Active Not Recruiting Phase 2

• 6 other identifiers: NCI-2012-019591106011736CDR00007123228854N01CM00070N01CM62204
• Study Type: interventional
• Target: 178
• Locations: 1 country
• Sites: 9

Brief Summary

This randomized phase II trial studies how well decitabine works when given together with daunorubicin hydrochloride and cytarabine in treating patients with acute myeloid leukemia. Drugs used in chemotherapy, such as decitabine, daunorubicin hydrochloride, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Decitabine may help daunorubicin hydrochloride and cytarabine kill more cancer cells by making them more sensitive to the drugs. It is not yet known whether low-dose decitabine is more effective than high-dose decitabine when giving together with daunorubicin hydrochloride and cytarabine in treating acute myeloid leukemia.

Conditions

Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Secondary Acute Myeloid Leukemia; Adult Acute Myeloid Leukemia With t(9;11)(p21.3;q23.3); MLLT3-KMT2A; Alkylating Agent-Related Acute Myeloid Leukemia; Acute Myeloid Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Myeloid Leukemia With Maturation

Outcome Measures

Primary Outcomes (1)

• Complete remission rate (CR1)

  After 1 course of decitabine-primed induction chemotherapy

Secondary Outcomes (6)

• Complete remission rate (CR1 + CR2)

  After up to 2 courses of decitabine-primed induction chemotherapy

• Overall survival

  Time from entry on study to time of death from any cause, assessed up to 10 years

• Relapse-free survival

  Time from CR documentation to either AML relapse or death from any cause, assessed up to 10 years

• Event-free survival

  Time from entry on study until treatment failure (no CR with up to two study induction cycles), AML relapse, or death from any cause, assessed up to 10 years

• Time to complete response determined according to the International Working Group (IWG) criterion

  Time from entry on study until documentation of CR, up to second course of induction chemotherapy

Study Arms (2)

Arm I (daunorubicin hydrochloride, cytarabine)

EXPERIMENTAL

Patients receive induction chemotherapy comprising daunorubicin hydrochloride IV daily on days 1-3 and cytarabine IV continuously on days 1-7 in the absence of disease progression or unacceptable toxicity. Patients who do not achieve a CR after the first induction-chemotherapy course receive a second identical induction course.

Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Arm II (decitabine, daunorubicin hydrochloride, cytarabine)

EXPERIMENTAL

Patients receive decitabine IV over 1 hour on days -5 to -1. Patients then receive induction chemotherapy as in arm I in the absence of disease progression or unacceptable toxicity. Patients who do not achieve a CR after the first induction-chemotherapy course receive a second identical induction course.

Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Drug: Decitabine; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Decitabine DRUG

Given IV

Also known as: 5-Aza-2'-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine

Arm II (decitabine, daunorubicin hydrochloride, cytarabine)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (daunorubicin hydrochloride, cytarabine); Arm II (decitabine, daunorubicin hydrochloride, cytarabine)

Pharmacological Study OTHER

Correlative studies

Arm I (daunorubicin hydrochloride, cytarabine); Arm II (decitabine, daunorubicin hydrochloride, cytarabine)

Cytarabine DRUG

Given IV

Also known as: .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, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Arm I (daunorubicin hydrochloride, cytarabine); Arm II (decitabine, daunorubicin hydrochloride, cytarabine)

Daunorubicin Hydrochloride DRUG

Given IV

Also known as: Cerubidin, Cerubidine, Cloridrato de Daunorubicina, Daunoblastin, Daunoblastina, Daunoblastine, Daunomycin Hydrochloride, Daunomycin, hydrochloride, Daunorubicin.HCl, Daunorubicini Hydrochloridum, FI-6339, Ondena, RP-13057, Rubidomycin Hydrochloride, Rubilem

Arm I (daunorubicin hydrochloride, cytarabine); Arm II (decitabine, daunorubicin hydrochloride, cytarabine)

Eligibility Criteria

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

You may qualify if:

• Diagnosis of acute myeloid leukemia (AML) as defined by the World Health Organization
• Molecular AML-risk group is less-than-favorable as defined by any of the following criteria:
• The absence of good-risk karyotype t(8;21), inv(16), t(16;16), or t(15;17)identified by metaphase karyotype
• The absence of t(8;21), inv(16), t(16;16), or t(15;17) identified by fluorescent in situ hybridization(FISH)
• The absence of the corresponding fusion transcripts, AML1-eight-twenty-one corepressor (ETO), core-binding factor, beta subunit (CBFβ)-smooth muscle myosin heavy chain (SMMHC), or progressive multifocal leukoencephalopathy (PML)-retinoic acid receptor alpha (RARa), identified by reverse transcriptase-polymerase chain reaction (RT-PCR)
• Patient does not have acute promyelocytic leukemia (APL, French-American-British \[FAB\] M3)
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
• Adequate cardiac function as defined by either of the following:
• An echocardiogram demonstrating an ejection fraction within normal limits
• A multi gated acquisition (MUGA) scan demonstrating an ejection fraction within normal limits
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) ≤ 2.5 times institutional upper limit of normal (ULN)
• Creatinine ≤ 2 mg/dL OR creatinine clearance ≥ 50 mL/min
• Total bilirubin ≤ 2 times ULN
• Patients with documented diagnosis of Gilbert syndrome resulting in elevated total bilirubin levels will be eligible, provided all other eligibility criteria are met
• Patients with a total bilirubin of 2-3 mg/dL and direct (conjugated) bilirubin in the normal range will be eligible, provided all other eligibility criteria are met

You may not qualify if:

• Chemotherapy (other than hydroxyurea) or radiation within the 2 weeks prior to planned therapy on this study or ongoing adverse events due to agents administered more than 2 weeks earlier
• Concurrent treatment with other investigational agents is not permitted
• Cumulative lifetime dose of anthracycline chemotherapeutic \> 80 mg/m\^2
• History of allergic reactions attributed to compounds of similar chemical or biologic composition of decitabine, cytarabine or daunorubicin
• Uncontrolled intercurrent illness considered by the investigator to constitute an unwarranted high risk for investigational drug treatment; examples include, but not limited to the following:
• Uncontrolled serious infection; or
• Unstable angina pectoris; or
• Uncontrolled cardiac arrhythmia; or
• Active second malignancy requiring treatment; or
• Symptomatic congestive heart failure
• HIV-positive subjects with a CD4 count \< 200 cells/μL are excluded due to the increased risk of lethal infections when treated with marrow-suppressive chemotherapy(87)
• NOTE: subjects with HIV infection and a CD4 count \>= 200 cells/μL are eligible but combination antiretroviral therapy should be held during administration of chemotherapy due to the potential for pharmacokinetic interactions with decita-bine, cytarabine or daunorubicin. Antiretroviral therapy may be resumed 24 hours after completion of the last dose of induction chemotherapy
• Subject has a psychiatric disorder, altered mental status or social situation that would preclude understanding of the informed consent process and/or limit compliance with study requirements
• Subject has an inability or unwillingness, in the opinion of the investigator, to comply with the protocol requirements
• Subjects with central nervous system (CNS) (or leptomeningeal) infiltration by AML may be considered for treatment at the Investigator's discretion and following discussion with the Principle Investigator; all neurologic deficits must be noted prior to enrollment on study

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (9)

Lafayette Family Cancer Center-EMMC

Brewer, Maine, 04412, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

NYP/Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Montefiore Medical Center-Weiler Hospital

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Basophilic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute

Interventions

Cytarabine; Daunorubicin; Decitabine; Injections

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Azacitidine; Aza Compounds; Ribonucleosides; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Joseph M Scandura

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2012
• First Posted: June 25, 2012
• Study Start: September 16, 2011
• Primary Completion: February 11, 2016
• Study Completion (Estimated): February 1, 2027
• Last Updated: April 27, 2026

Record last verified: 2026-04

Locations

US (9)