Decitabine as Maintenance Therapy After Standard Therapy in Treating Patients With Previously Untreated Acute Myeloid Leukemia

NCT ID: NCT00416598

Last Updated: 2019-02-19

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

546 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-11-15

Study Completion Date

2016-12-01

Brief Summary

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This phase II trial is studying the side effects and how well decitabine works when given as maintenance therapy after standard therapy in treating patients with previously untreated acute myeloid leukemia. Drugs used in chemotherapy, such as cytarabine, daunorubicin, etoposide, busulfan, and decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving decitabine as maintenance therapy after standard therapy may keep cancer cells from coming back.

Detailed Description

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PRIMARY OBJECTIVES:

I. To determine the efficacy, feasibility, and toxicities when one year of maintenance therapy with decitabine is given to patients \< 60 years with untreated acute myeloid leukemia (AML) who achieve and maintain first complete remission (CR) following an established induction and intensification regimen.

II. To determine the 1-year disease free survival rate for AML patients in first CR treated with maintenance decitabine.

SECONDARY OBJECTIVES:

I. To measure biologic response to decitabine in evaluable patients with fusion genes to determine eradication of minimal residual disease.

II. To measure surrogates for deoxyribonucleic acid (DNA) demethylation including downregulation of DNA methyltransferase 1 (DNMT1) and induction of fetal hemoglobin.

III. To examine the significance of gene re expression following ex vivo decitabine exposure in primary AML cells taken at the time of diagnosis on clinical outcome and on gene expression at the time of relapse after in vivo decitabine exposure.

IV. To continue to evaluate the effectiveness of a cytogenetically risk-adapted approach for consolidation therapy for patients with core binding factor (CBF) or non-CBF AML.

V. To continue the investigation begun in Cancer and Leukemia Group B (CALGB) 19808 aimed at correlation of the rate of relapse and toxicity with intravenous (IV) busulfan pharmacokinetics when busulfan and etoposide are used as the preparative regimen for autologous stem cell transplantation for AML patients in first CR.

VI. To correlate outcome measures such as complete response (CR), disease-free survival (DFS), event-free survival (EFS), and overall survival (OS), with pretreatment characteristics such as age, sex, race, blood counts, morphology, immunophenotype, cytogenetics, and molecular features of AML.

OUTLINE:

REMISSION INDUCTION THERAPY: Patients receive cytarabine IV over 168 hours on days 1-7 and daunorubicin hydrochloride IV over 5-10 minutes and etoposide IV over 2 hours on days 1-3. Patients undergo bone marrow biopsy on day 14. Patients with residual leukemia proceed to second remission induction therapy. Patients achieving complete remission (CR) proceed to intensification therapy.

SECOND REMISSION INDUCTION THERAPY: Patients receive cytarabine IV over 120 hours on days 1-5 and daunorubicin hydrochloride IV and etoposide IV over 2 hours on days 1 and 2. Patients undergo bone marrow biopsy on day 42. Patients with residual leukemia are removed from the study. Patients achieving CR proceed to intensification therapy.

INTENSIFICATION THERAPY: Patients are stratified and receive intensification therapy according to cytogenetic findings (favorable cytogenetics \[t(8;21)(q22q22), inv(16)(p13;q22), or t(16;16)(p13;q22) by cytogenetic and/or molecular analysis\] vs unfavorable cytogenetics \[all other cytogenetic findings, including normal cytogenetics\]).

FAVORABLE CYTOGENETICS: Within 2-4 weeks after achieving CR, patients receive high-dose cytarabine IV over 3 hours twice daily on days 1, 3, and 5.

Treatment repeats every 28 days for up to 3 courses.

UNFAVORABLE CYTOGENETICS: Peripheral blood stem cell (PBSC) mobilization: Within 2-4 weeks after achieving CR, patients receive etoposide IV over 96 hours and high-dose cytarabine IV over 2 hours twice daily on days 1-4 and filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 14 and continuing until blood counts recover. Patients then proceed to transplantation.

PBSC OR BONE MARROW TRANSPLANTATION: Patients receive busulfan IV over 2 hours 4 times daily on days -7 to -4 and etoposide IV over 4 hours on day -3. Patients undergo autologous PBSC or bone marrow transplantation on day 0 and receive G-CSF SC once daily beginning on day 0 and continuing until blood counts recover.

UNFAVORABLE CYTOGENETICS AND UNABLE TO UNDERGO PBSC TRANSPLANTATION: Within 2-4 weeks after achieving CR, patients receive etoposide, high-dose cytarabine, and G-CSF as in unfavorable cytogenetics (PBSC mobilization) followed by 2 courses of high-dose cytarabine as in favorable genetics.

MAINTENANCE THERAPY: Within 60-90 days after completion of intensification therapy, patients receive decitabine IV over 1 hour on days 1-5. Treatment repeats every 6 weeks for up to 8 courses.

After completion of study treatment, patients are followed up every 2 months for 1 year, every 6 months for 2 years, and then yearly for 2 years.

Conditions

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Acute Myeloid Leukemia Acute Myeloid Leukemia With Myelodysplasia-Related Changes Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11 Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11 Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1 Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A Untreated Adult Acute Myeloid Leukemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (chemotherapy, PBSC or bone marrow transplantation)

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Group Type EXPERIMENTAL

Autologous Bone Marrow Transplantation

Intervention Type PROCEDURE

Undergo autologous bone marrow transplantation

Autologous Hematopoietic Stem Cell Transplantation

Intervention Type PROCEDURE

Undergo autologous PBSC transplantation

Busulfan

Intervention Type DRUG

Given IV

Cytarabine

Intervention Type DRUG

Given IV

Daunorubicin Hydrochloride

Intervention Type DRUG

Given IV

Decitabine

Intervention Type DRUG

Given IV

Etoposide

Intervention Type DRUG

Given IV

Filgrastim

Intervention Type BIOLOGICAL

Given SC

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pharmacological Study

Intervention Type OTHER

Correlative studies

Interventions

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Autologous Bone Marrow Transplantation

Undergo autologous bone marrow transplantation

Intervention Type PROCEDURE

Autologous Hematopoietic Stem Cell Transplantation

Undergo autologous PBSC transplantation

Intervention Type PROCEDURE

Busulfan

Given IV

Intervention Type DRUG

Cytarabine

Given IV

Intervention Type DRUG

Daunorubicin Hydrochloride

Given IV

Intervention Type DRUG

Decitabine

Given IV

Intervention Type DRUG

Etoposide

Given IV

Intervention Type DRUG

Filgrastim

Given SC

Intervention Type BIOLOGICAL

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Pharmacological Study

Correlative studies

Intervention Type OTHER

Other Intervention Names

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ABMT Autologous Bone Marrow Transplant Autologous Marrow Transplantation Autologous Hematopoietic Cell Transplantation autologous stem cell transplantation 1, 4-Bis[methanesulfonoxy]butane BUS Bussulfam Busulfanum Busulfex Busulphan CB 2041 CB-2041 Glyzophrol GT 41 GT-41 Joacamine Methanesulfonic Acid Tetramethylene Ester Methanesulfonic acid, tetramethylene ester Mielucin Misulban Misulfan Mitosan Myeleukon Myeloleukon Myelosan Mylecytan Myleran Sulfabutin Tetramethylene Bis(methanesulfonate) Tetramethylene bis[methanesulfonate] WR-19508 .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 Cerubidin Cerubidine Cloridrato de Daunorubicina Daunoblastin Daunoblastina Daunoblastine Daunomycin Hydrochloride Daunomycin, hydrochloride Daunorubicin.HCl Daunorubicini Hydrochloridum FI-6339 Ondena RP-13057 Rubidomycin Hydrochloride Rubilem 5-Aza-2'-deoxycytidine Aza-TdC Dacogen Decitabine for Injection Deoxyazacytidine Dezocitidine Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16-213 VP-16 VP-16-213 FILGRASTIM, LICENSE HOLDER UNSPECIFIED G-CSF Neupogen r-metHuG-CSF Recombinant Methionyl Human Granulocyte Colony Stimulating Factor rG-CSF Tevagrastim

Eligibility Criteria

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Inclusion Criteria

* Unequivocal histologic diagnosis of AML (\> 20% blasts in the bone marrow based on the World Health Organization \[WHO\] and/or French American British \[FAB\] classifications), excluding M3 (acute promyelocytic leukemia); patients with antecedent myelodysplasia are eligible for treatment on this trial only if there were no bone marrow biopsy showing myelodysplastic syndrome (MDS) \> 3 months prior to enrollment; patients with therapy-related AML are eligible if they have been free of their primary disease and have not received any chemotherapy for at least 2 years
* No prior 5-azacitidine or decitabine therapy
* No prior treatment for leukemia or myelodysplastic syndrome with four permissible exceptions:

* Emergency leukapheresis
* Emergency treatment for hyperleukocytosis with hydroxyurea
* Cranial radiation therapy (RT) for central nervous system (CNS) leukostasis (one dose only)
* Growth factor/cytokine support
Minimum Eligible Age

15 Years

Maximum Eligible Age

59 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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William Blum

Role: PRINCIPAL_INVESTIGATOR

Alliance for Clinical Trials in Oncology

Locations

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UCSF Medical Center-Mount Zion

San Francisco, California, United States

Site Status

Beebe Medical Center

Lewes, Delaware, United States

Site Status

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States

Site Status

Florida Hospital Orlando

Orlando, Florida, United States

Site Status

Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, United States

Site Status

University of Illinois

Chicago, Illinois, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, United States

Site Status

Fort Wayne Medical Oncology and Hematology Inc-Parkview

Fort Wayne, Indiana, United States

Site Status

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Site Status

Eastern Maine Medical Center

Bangor, Maine, United States

Site Status

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

Site Status

Walter Reed National Military Medical Center

Bethesda, Maryland, United States

Site Status

Union Hospital of Cecil County

Elkton, Maryland, United States

Site Status

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Commonwealth Hematology Oncology PC-Worcester

Worcester, Massachusetts, United States

Site Status

Veterans Administration

Columbia, Missouri, United States

Site Status

University of Missouri - Ellis Fischel

Columbia, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Great Plains Health Callahan Cancer Center

North Platte, Nebraska, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

University Medical Center of Southern Nevada

Las Vegas, Nevada, United States

Site Status

Nevada Cancer Research Foundation CCOP

Las Vegas, Nevada, United States

Site Status

Sunrise Hospital and Medical Center

Las Vegas, Nevada, United States

Site Status

Cheshire Medical Center-Dartmouth-Hitchcock Keene

Keene, New Hampshire, United States

Site Status

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Cooper Hospital University Medical Center

Camden, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Northwell Health NCORP

Lake Success, New York, United States

Site Status

Northwell Health/Center for Advanced Medicine

Lake Success, New York, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

Long Island Jewish Medical Center

New Hyde Park, New York, United States

Site Status

Mount Sinai Hospital

New York, New York, United States

Site Status

State University of New York Upstate Medical University

Syracuse, New York, United States

Site Status

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status

Wayne Memorial Hospital

Goldsboro, North Carolina, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

West Penn Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Miriam Hospital

Providence, Rhode Island, United States

Site Status

Central Vermont Medical Center/National Life Cancer Treatment

Berlin Corners, Vermont, United States

Site Status

University of Vermont College of Medicine

Burlington, Vermont, United States

Site Status

Countries

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United States

References

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Seffernick AE, Mrozek K, Nicolet D, Stone RM, Eisfeld AK, Byrd JC, Archer KJ. High-dimensional genomic feature selection with the ordered stereotype logit model. Brief Bioinform. 2022 Nov 19;23(6):bbac414. doi: 10.1093/bib/bbac414.

Reference Type DERIVED
PMID: 36184192 (View on PubMed)

Yin J, LaPlant B, Uy GL, Marcucci G, Blum W, Larson RA, Stone RM, Mandrekar SJ. Evaluation of event-free survival as a robust end point in untreated acute myeloid leukemia (Alliance A151614). Blood Adv. 2019 Jun 11;3(11):1714-1721. doi: 10.1182/bloodadvances.2018026112.

Reference Type DERIVED
PMID: 31171508 (View on PubMed)

Blum W, Sanford BL, Klisovic R, DeAngelo DJ, Uy G, Powell BL, Stock W, Baer MR, Kolitz JE, Wang ES, Hoke E, Mrozek K, Kohlschmidt J, Bloomfield CD, Geyer S, Marcucci G, Stone RM, Larson RA; Alliance for Clinical Trials in Oncology. Maintenance therapy with decitabine in younger adults with acute myeloid leukemia in first remission: a phase 2 Cancer and Leukemia Group B Study (CALGB 10503). Leukemia. 2017 Jan;31(1):34-39. doi: 10.1038/leu.2016.252. Epub 2016 Sep 13.

Reference Type DERIVED
PMID: 27624549 (View on PubMed)

Other Identifiers

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NCI-2009-00444

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000521603

Identifier Type: -

Identifier Source: secondary_id

CALGB 10503

Identifier Type: OTHER

Identifier Source: secondary_id

CALGB-10503

Identifier Type: OTHER

Identifier Source: secondary_id

R21CA128377

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA180821

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00444

Identifier Type: -

Identifier Source: org_study_id

NCT01647074

Identifier Type: -

Identifier Source: nct_alias

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