Efficacy of 400 Mg Versus 800 Mg Imatinib in Chronic Myeloid Leukemia in Chronic Phase Patients - TOPS (Tyrosine Kinase Inhibitor Optimization and Selectivity)

NCT ID: NCT00124748

Last Updated: 2012-02-03

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

476 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-06-30

Study Completion Date

2010-11-30

Brief Summary

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This study investigated the safety and efficacy of 400mg Versus 800mg imatinib in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase (CML-CP) using molecular endpoints.

Detailed Description

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Conditions

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Leukemia, Myeloid, Chronic Phase

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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Imatinib 400 mg

Oral dose of 400mg Imatinib once daily. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.

Group Type EXPERIMENTAL

Imatinib mesylate

Intervention Type DRUG

Imatinib is packaged in bottles as 100mg and 400mg tablets

imatinib 800 mg

Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.

Group Type EXPERIMENTAL

Imatinib mesylate

Intervention Type DRUG

Imatinib is packaged in bottles as 100mg and 400mg tablets

Interventions

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Imatinib mesylate

Imatinib is packaged in bottles as 100mg and 400mg tablets

Intervention Type DRUG

Other Intervention Names

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STI571 Gleevec Glivec

Eligibility Criteria

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Inclusion Criteria

* Patients within 6 months of diagnosis (date of initial diagnosis is the date of first cytogenetic analysis)
* Diagnosis of chronic myelogenous leukemia (CML) in chronic phase with cytogenetic confirmation of Philadelphia chromosome of (9;22) translocations and presence of Breakpoint cluster region gene-abelson proto-oncogene (Bcr-Abl)
* Documented chronic phase CML
* Adequate end organ function as defined by:

* total bilirubin \< 1.5 x Upper Limit of Normal (ULN)
* Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) \< 2.5 x ULN
* creatinine \< 1.5 x ULN

Exclusion Criteria

* Patients in late chronic phase, accelerated phase, or blastic phase are excluded
* Patients who have received other investigational agents
* Patients who received Gleevec/Glivec for any duration prior to study entry, with the exception of those patients successfully completing \[CSTI571A2107 (NCT00428909)\] study immediately prior to the participation in this study
* Patient received any treatment for CML prior to study entry for longer than 2 weeks with the exception of hydroxyurea and/or anagrelide
* Patients with another primary malignancy except if the other primary malignancy is neither currently clinically significant or requiring active intervention
* Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential without a negative pregnancy test prior to baseline and (d) male or female of childbearing potential unwilling to use barrier contraceptive precautions throughout the trial (post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential).
* Patient with a severe or uncontrolled medical condition (i.e., uncontrolled diabetes,chronic renal disease)
* Patient previously received radiotherapy to ≥ 25% of the bone marrow
* Patient had major surgery within 4 weeks prior to study entry, or who have not recovered from prior major surgery
* Patients with an Eastern Cooperative Oncology Group (ECOG) Performance Status Score ≥ 3
* Patients with International normalized ratio (INR) or partial thromboplastin time (PTT) \> 1.5 x ULN, with the exception of patients on treatment with oral anticoagulants
* Patients with known positivity for human immunodeficiency virus (HIV); baseline testing for HIV is not required
* Patients with identified sibling donors where allogeneic bone marrow transplant is elected as first line treatment
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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University of South Alabama

Mobile, Alabama, United States

Site Status

Alta Bates Comprehsenive Cancer Center

Berkeley, California, United States

Site Status

University of Miami

Berkeley, California, United States

Site Status

South Bay Oncology Hematology Partners

Campbell, California, United States

Site Status

UCLA Medical Center

Los Angeles, California, United States

Site Status

Rocky Mountain Cancer Center

Denver, Colorado, United States

Site Status

Osler Medical Inc.

Melbourne, Florida, United States

Site Status

Advanced Medical Specialists

Miami, Florida, United States

Site Status

Integrated Community Oncology Network

Orange Park, Florida, United States

Site Status

Hematology-Oncology Associates, P.A.

Pensacola, Florida, United States

Site Status

Palm Beach Cancer Institute

West Palm Beach, Florida, United States

Site Status

Palm Beach Cancer Institute

West Palm Beach, Florida, United States

Site Status

Cancer Research Center of Hawaii

Honolulu, Hawaii, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Indiana Blood and Marrow Institutw

Beech Grove, Indiana, United States

Site Status

Indiana Blood and Marrow Transplant

Beech Grove, Indiana, United States

Site Status

University of Iowa Hospitals & Clinic

Iowa City, Iowa, United States

Site Status

University of Kentucky - C201 Clinic

Lexington, Kentucky, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

Lousville Oncology, Clinical Research Program M-25

Louisville, Kentucky, United States

Site Status

Jayne S. Gurtler, MD, Laura A. Brinz, MD & Angelo Russo, MD

Metairie, Louisiana, United States

Site Status

Hematology and Oncology Specialists

New Orleans, Louisiana, United States

Site Status

LSU Health Science Center

Shreveport, Louisiana, United States

Site Status

LSU Health Scine Center

Shreveport, Louisiana, United States

Site Status

St. Agnes Hospital

Baltimore, Maryland, United States

Site Status

Great Lakes Cancer Institute

Lansing, Michigan, United States

Site Status

U of Minnesota

Minneapolis, Minnesota, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

San Juan Oncology Associates

Farmington, New Mexico, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Cancer Center of the Carolinas

Greenville, North Carolina, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

University Hospitals of Cleveland, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Kaiser Permanente Northwest Region Oncology/Hemacology

Portland, Oregon, United States

Site Status

Kaiser Permanente Northwest Region

Portland, Oregon, United States

Site Status

Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, United States

Site Status

University of Pittsburg, Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

MUSC Hollings Cancer Center

Charleston, South Carolina, United States

Site Status

Cancer Center of the Carolinas

Greenville, South Carolina, United States

Site Status

Cancer Centers of the Carolinas

Greenville, South Carolina, United States

Site Status

The Jones Clinic

Germantown, Tennessee, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

UT Southwestern Harold C. Simmons Comprehensive Cancer Center

Dallas, Texas, United States

Site Status

University of Texas / MD Anderson Cancer Center

Houston, Texas, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

University of Virgina Cancer Center, UVA Division of Hematology & Oncology

Charlottesville, Virginia, United States

Site Status

Novartis Investigative Site

Buenos Aires, , Argentina

Site Status

Novartis Investigative Site

La Plata, , Argentina

Site Status

Novartis Investigative Site

St Leonards, New South Wales, Australia

Site Status

Novartis Investigative Site

Waratah, New South Wales, Australia

Site Status

Novartis Investigative Site

Westmead, New South Wales, Australia

Site Status

Novartis Investigative Site

Herston, Queensland, Australia

Site Status

Novartis Investigative Site

Woolloongabba, Queensland, Australia

Site Status

Novartis Investigative Site

Adelaide, South Australia, Australia

Site Status

Novartis Investigative Site

East Melbourne, Victoria, Australia

Site Status

Novartis Investigative Site

Fitzroy, Victoria, Australia

Site Status

Novartis Investigative Site

Frankston, Victoria, Australia

Site Status

Novartis Investigative Site

Parkville, Victoria, Australia

Site Status

Novartis Investigative Site

Prahran, Victoria, Australia

Site Status

Novartis Investigative Site

South Brisbane, , Australia

Site Status

Novartis Investigative Site

Campinas, , Brazil

Site Status

Novartis Investigative Site

Calgary, , Canada

Site Status

Novartis Investigative Site

Montreal, , Canada

Site Status

Novartis Investigative Site

Ottawa, , Canada

Site Status

Novartis Investigative Site

Québec, , Canada

Site Status

Novartis Investigative Site

Bologna, , Italy

Site Status

Novartis Investigative Site

Florence, , Italy

Site Status

Novartis Investigative Site

Milan, , Italy

Site Status

Novartis Investigative Site

Napoli, , Italy

Site Status

Novartis Investigative Site

Orbassano, , Italy

Site Status

Novartis Investigative Site

Roma, , Italy

Site Status

Countries

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United States Argentina Australia Brazil Canada Italy

References

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Branford S, Yeung DT, Parker WT, Roberts ND, Purins L, Braley JA, Altamura HK, Yeoman AL, Georgievski J, Jamison BA, Phillis S, Donaldson Z, Leong M, Fletcher L, Seymour JF, Grigg AP, Ross DM, Hughes TP. Prognosis for patients with CML and >10% BCR-ABL1 after 3 months of imatinib depends on the rate of BCR-ABL1 decline. Blood. 2014 Jul 24;124(4):511-8. doi: 10.1182/blood-2014-03-566323. Epub 2014 May 23.

Reference Type DERIVED
PMID: 24859364 (View on PubMed)

Branford S, Yeung DT, Ross DM, Prime JA, Field CR, Altamura HK, Yeoman AL, Georgievski J, Jamison BA, Phillis S, Sullivan B, Briggs NE, Hertzberg M, Seymour JF, Reynolds J, Hughes TP. Early molecular response and female sex strongly predict stable undetectable BCR-ABL1, the criteria for imatinib discontinuation in patients with CML. Blood. 2013 May 9;121(19):3818-24. doi: 10.1182/blood-2012-10-462291. Epub 2013 Mar 20.

Reference Type DERIVED
PMID: 23515925 (View on PubMed)

Guilhot F, Hughes TP, Cortes J, Druker BJ, Baccarani M, Gathmann I, Hayes M, Granvil C, Wang Y. Plasma exposure of imatinib and its correlation with clinical response in the Tyrosine Kinase Inhibitor Optimization and Selectivity Trial. Haematologica. 2012 May;97(5):731-8. doi: 10.3324/haematol.2011.045666. Epub 2012 Feb 7.

Reference Type DERIVED
PMID: 22315495 (View on PubMed)

Related Links

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http://www.novartisclinicaltrials.com

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Other Identifiers

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CSTI571K2301

Identifier Type: -

Identifier Source: org_study_id

NCT00324636

Identifier Type: -

Identifier Source: nct_alias

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