Decitabine With or Without Bortezomib in Treating Older Patients With Acute Myeloid Leukemia

NCT ID: NCT01420926

Last Updated: 2023-02-28

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

165 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-11-16

Study Completion Date

2021-04-01

Brief Summary

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This randomized phase II trial studies how well giving decitabine with or without bortezomib works in treating older patients with acute myeloid leukemia. Drugs used in chemotherapy, such as 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. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether decitabine works better when given with or without bortezomib in treating acute myeloid leukemia.

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Detailed Description

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PRIMARY OBJECTIVE:

I. To determine if treatment of older acute myeloid leukemia (AML) patients with decitabine and bortezomib significantly improves the overall survival times of older AML patients compared with decitabine alone.

SECONDARY OBJECTIVES:

I. To determine the rate of complete remission (CR and CR + incomplete blood count recovery \[CRi\]) for each of the 2 treatment regimens in the proposal.

II. To determine the overall survival, progression-free survival, disease-free survival and for each of the treatment regimens on this study.

III. To determine whether ongoing treatment with these regimens prolongs overall survival even in the absence of complete remission.

IV. To describe the frequency and severity of adverse events, as well as the tolerability of each of these regimens in patients treated on this study.

V. To describe the interaction of pretreatment disease and patient characteristics including morphology, cytogenetics, molecular genetics, white blood cell (WBC) count, blood and bone marrow blast count, age, performance status and comprehensive geriatric assessment on clinical outcomes.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: REMISSION INDUCTION THERAPY: Patients receive decitabine intravenously (IV) over 1 hour once daily (QD) on days 1-10. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CR with CRi proceed to continuation therapy. Patients achieving CR or CR with CRi proceed to maintenance therapy.

CONTINUATION THERAPY: Patients receive decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: REMISSION INDUCTION THERAPY: Patients receive decitabine IV over 1 hour QD on days 2-11 and bortezomib subcutaneously (SC) on days 1, 4, 8, and 11. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CRi proceed to continuation therapy. Patients achieving CR or CR with CRi proceed to maintenance therapy.

CONTINUATION THERAPY: Patients receive bortezomib SC on day 1 and decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive bortezomib SC on day 1 and decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months for 2 years, every 3 months for 2 years, and then once a year for a maximum of 10 years from study entry.

Conditions

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Acute Myeloid Leukemia Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome Therapy-Related Acute Myeloid Leukemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A (decitabine)

REMISSION INDUCTION THERAPY: Patients receive 20 mg/m\^2 decitabine IV over 1 hour QD on days 1-10. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR CRi proceed to continuation therapy. Patients achieving CR or CRi proceed to maintenance therapy.

CONTINUATION THERAPY: Patients receive 20 mg/m\^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive 20 mg/m\^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Decitabine

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pharmacological Study

Intervention Type OTHER

Correlative studies

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Arm B (decitabine and bortezomib)

REMISSION INDUCTION THERAPY: Patients receive 20 mg/m\^2 decitabine IV over 1 hour QD on days 2-11 and 1.3 mg/m\^2 bortezomib SC on days 1, 4, 8, and 11. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CRi proceed to continuation therapy. Patients achieving CR or CRi proceed to maintenance therapy.

CONTINUATION THERAPY: Patients receive 1.3 mg/m\^2 bortezomib SC on day 1 and 20 mg/m\^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive 1.3 mg/m\^2 bortezomib SC on day 1 and 20 mg/m\^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Bortezomib

Intervention Type DRUG

Given SC

Decitabine

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pharmacological Study

Intervention Type OTHER

Correlative studies

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Interventions

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Bortezomib

Given SC

Intervention Type DRUG

Decitabine

Given IV

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Pharmacological Study

Correlative studies

Intervention Type OTHER

Quality-of-Life Assessment

Ancillary studies

Intervention Type OTHER

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Other Intervention Names

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[(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid LDP 341 MLN341 PS-341 PS341 Velcade 5-Aza-2'-deoxycytidine Dacogen Decitabine for Injection Deoxyazacytidine Dezocitidine Quality of Life Assessment

Eligibility Criteria

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Inclusion Criteria

* Unequivocal pathologic diagnosis of AML (\>= 20% blasts in the bone marrow based on World Health Organization \[WHO\] criteria) EXCLUDING:

* Acute promyelocytic leukemia t(15;17)(q22;q12); PML-RARA
* Acute myeloid leukemia with t(8;21)(q22;q22); RUNX1-RUNXT1 as determined by the Ohio State University (OSU) Molecular Reference Laboratory, per Cancer and Leukemia Group B (CALGB) 20202; however patients who (1) are \>= 75 years; and/or (2) have an ejection fraction of \< 40%; and/or (3) have a performance status of \> 2, may be registered to CALGB 20202 and registered and treated on CALGB 11002 prior to receiving the FLT3 mutation and core-binding factor (CBF) molecular screening results from CALGB 20202
* Acute myeloid leukemia with inv(16)(p13.1;q22) or t(16;16)(p13.1;q22); CBFB-MYH11 as determined by the OSU Molecular Reference Laboratory, per CALGB 20202; however patients who (1) are \>= 75 years; and/or (2) have an ejection fraction of \< 40%; and/or (3) have a performance status of \> 2, may be registered to CALGB 20202 and registered and treated on CALGB 11002 prior to receiving the FLT3 mutation and CBF molecular screening results from CALGB 20202
* Absence of FLT3 mutation (ITD or point mutation) determined by the OSU Molecular Reference Laboratory, per CALGB 20202; however patients who (1) are \>= 75 years; and/or (2) have an ejection fraction of \< 40%; and/or (3) have a performance status of \> 2, may be registered to CALGB 20202 and registered and treated on CALGB 11002 prior to receiving the FLT3 mutation and CBF molecular screening results from CALGB 20202
* No prior treatment for AML except:

* Emergency leukapheresis
* Emergency treatment for hyperleukocytosis with hydroxyurea
* Cranial radiotherapy (RT) for central nervous system (CNS) leukostasis (one dose only)
* Growth factor/cytokine support
* AML patients with an antecedent hematologic disorder (AHD) or myelodysplastic syndrome (MDS) are eligible for this trial provided that they have not received treatment for their AHD or MDS with cytotoxic chemotherapy (e.g., cytarabine, daunorubicin, etc.), decitabine, or bortezomib; patients may have been previously treated with azacitidine if their last dose was \>= 90 days prior to starting 11002
* AML patients with therapy-related myeloid neoplasms (t-MN) are eligible if they have not received radiation therapy or chemotherapy (not including hormonal therapy) for their primary malignancy or disorder for \> 6 months
Minimum Eligible Age

60 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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Gail J Roboz

Role: PRINCIPAL_INVESTIGATOR

Alliance for Clinical Trials in Oncology

Locations

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Palo Alto Medical Foundation-Camino Division

Mountain View, California, United States

Site Status

Hartford Hospital

Hartford, Connecticut, 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

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

AdventHealth Orlando

Orlando, Florida, 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

Harold Alfond Center for Cancer Care

Augusta, Maine, United States

Site Status

Eastern Maine Medical Center

Bangor, Maine, United States

Site Status

Christiana Care - Union Hospital

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

Bronson Battle Creek

Battle Creek, Michigan, United States

Site Status

Spectrum Health Big Rapids Hospital

Big Rapids, Michigan, United States

Site Status

Cancer Research Consortium of West Michigan NCORP

Grand Rapids, Michigan, United States

Site Status

Mercy Health Saint Mary's

Grand Rapids, Michigan, United States

Site Status

Spectrum Health at Butterworth Campus

Grand Rapids, Michigan, United States

Site Status

Mercy Health Mercy Campus

Muskegon, Michigan, United States

Site Status

Spectrum Health Reed City Hospital

Reed City, Michigan, United States

Site Status

Munson Medical Center

Traverse City, Michigan, United States

Site Status

University of Missouri - Ellis Fischel

Columbia, Missouri, 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

NYP/Weill Cornell Medical Center

New York, New York, United States

Site Status

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

Site Status

Wayne Memorial Hospital

Goldsboro, North Carolina, United States

Site Status

East Carolina University

Greenville, North Carolina, United States

Site Status

Margaret R Pardee Memorial Hospital

Hendersonville, North Carolina, United States

Site Status

Vidant Oncology-Kinston

Kinston, 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

Cancer Care Associates-Norman

Norman, Oklahoma, United States

Site Status

Mercy Hospital Oklahoma City

Oklahoma City, Oklahoma, United States

Site Status

Prisma Health Cancer Institute - Spartanburg

Boiling Springs, South Carolina, United States

Site Status

Prisma Health Cancer Institute - Butternut

Greenville, South Carolina, United States

Site Status

Prisma Health Cancer Institute - Faris

Greenville, South Carolina, United States

Site Status

Prisma Health Greenville Memorial Hospital

Greenville, South Carolina, United States

Site Status

Prisma Health Cancer Institute - Eastside

Greenville, South Carolina, United States

Site Status

Prisma Health Cancer Institute - Greer

Greer, South Carolina, United States

Site Status

Prisma Health Cancer Institute - Seneca

Seneca, South Carolina, United States

Site Status

Central Vermont Medical Center/National Life Cancer Treatment

Berlin Corners, Vermont, United States

Site Status

University of Vermont and State Agricultural College

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)

Ritchie EK, Klepin HD, Storrick E, Major B, Le-Rademacher J, Wadleigh M, Walker A, Larson RA, Roboz GJ. Geriatric assessment for older adults receiving less-intensive therapy for acute myeloid leukemia: report of CALGB 361101. Blood Adv. 2022 Jun 28;6(12):3812-3820. doi: 10.1182/bloodadvances.2021006872.

Reference Type DERIVED
PMID: 35420672 (View on PubMed)

Roboz GJ, Mandrekar SJ, Desai P, Laumann K, Walker AR, Wang ES, Kolitz JE, Powell BL, Attar EC, Stock W, Bloomfield CD, Kohlschmidt J, Mrozek K, Hassane DC, Garraway L, Jane-Valbuena J, Baltay M, Tracy A, Marcucci G, Stone RM, Larson RA. Randomized trial of 10 days of decitabine +/- bortezomib in untreated older patients with AML: CALGB 11002 (Alliance). Blood Adv. 2018 Dec 26;2(24):3608-3617. doi: 10.1182/bloodadvances.2018023689.

Reference Type DERIVED
PMID: 30567725 (View on PubMed)

Other Identifiers

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NCI-2011-02987

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000709218

Identifier Type: -

Identifier Source: secondary_id

CALGB-11002

Identifier Type: OTHER

Identifier Source: secondary_id

CALGB-11002

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180821

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-02987

Identifier Type: -

Identifier Source: org_study_id

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